Skip to main content

2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

Clinical Practice Guideline: Executive Summary

J Am Coll Cardiol, 64 (24) 2645–2687
Sections

ACC/AHA Task Force Members

Jeffrey L. Anderson, MD, FACC, FAHA, Chair

Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect

Nancy M. Albert, PhD, RN, FAHA

Biykem Bozkurt, MD, PhD, FACC, FAHA

Ralph G. Brindis, MD, MPH, MACC

Lesley H. Curtis, PhD, FAHA

David DeMets, PhD††

Lee A. Fleisher, MD, FACC, FAHA

Samuel Gidding, MD, FAHA

Robert A. Guyton, MD, FACC††

Judith S. Hochman, MD, FACC, FAHA††

Richard J. Kovacs, MD, FACC, FAHA

E. Magnus Ohman, MD, FACC

Susan J. Pressler, PhD, RN, FAHA

Frank W. Sellke, MD, FACC, FAHA

Win-Kuang Shen, MD, FACC, FAHA

William G. Stevenson, MD, FACC, FAHA††

Duminda N. Wijeysundera, MD, PhD

Clyde W. Yancy, MD, FACC, FAHA††

Former Task Force member; current member during the writing effort.

Table of Contents

Preamble2647

1.

Introduction2649

1.1.

Methodology and Evidence Review2649

1.2.

Organization of the GWC2649

1.3.

Document Review and Approval2649

1.4.

Scope of the CPG2650

2.

Overview of ACS2650

3.

Initial Evaluation and Management: Recommendations2650

3.1.

Clinical Assessment and Initial Evaluation2650

3.2.

Emergency Department or Outpatient Facility Presentation2650

3.3.

Prognosis—Early Risk Stratification2650

3.4.

Cardiac Biomarkers and the Universal Definition of Myocardial Infarction2654

3.4.1.

Biomarkers: Diagnosis2654

3.4.2.

Biomarkers: Prognosis2654

3.5.

Discharge From the ED or Chest Pain Unit2655

4.

Early Hospital Care: Recommendations2655

4.1.

Standard Medical Therapies2655

4.1.1.

Oxygen2655

4.1.2.

Nitrates2655

4.1.3.

Analgesic Therapy2655

4.1.4.

Beta-Adrenergic Blockers2656

4.1.5.

Calcium Channel Blockers2657

4.1.6.

Cholesterol Management2657

4.2.

Inhibitors of the Renin-Angiotensin-Aldosterone System2657

4.3.

Initial Antiplatelet/Anticoagulant Therapy in Patients With Definite or Likely NSTE-ACS2657

4.3.1.

Initial Oral and Intravenous Antiplatelet Therapy in Patients With Definite or Likely NSTE-ACS Treated With an Initial Invasive or Ischemia-Guided Strategy2657

4.3.2.

Initial Parenteral Anticoagulant Therapy in Patients With Definite NSTE-ACS2659

4.4.

Ischemia-Guided Strategy Versus Early Invasive Strategies2659

4.4.1.

Early Invasive and Ischemia-Guided Strategies2659

4.5.

Risk Stratification Before Discharge for Patients With an Ischemia-Guided Strategy of NSTE-ACS2661

5.

Myocardial Revascularization: Recommendations2661

5.1.

PCI—General Considerations2661

5.1.1.

PCI—Oral and Intravenous Antiplatelet Agents2661

5.1.1.1.

PCI—GP IIb/IIIa Inhibitors2662

5.1.2.

Anticoagulant Therapy in Patients Undergoing PCI2663

5.2.

Timing of Urgent Coronary Artery Bypass Graft in Patients With NSTE-ACS in Relation to Use of Antiplatelet Agents2663

6.

Late Hospital Care, Hospital Discharge, and Posthospital Discharge Care: Recommendations2663

6.1.

Medical Regimen and Use of Medications at Discharge2663

6.2.

Late Hospital and Posthospital Oral Antiplatelet Therapy2664

6.3.

Combined Oral Anticoagulant Therapy and Antiplatelet Therapy in Patients With NSTE-ACS2664

6.4.

Risk Reduction Strategies for Secondary Prevention2664

6.5.

Plan of Care for Patients With NSTE-ACS2665

7.

Special Patient Groups: Recommendations2665

7.1.

NSTE-ACS in Older Patients2665

7.2.

Heart Failure and Cardiogenic Shock2665

7.3.

Diabetes Mellitus2667

7.4.

Post–CABG2668

7.5.

Perioperative NSTE-ACS Related to Noncardiac Surgery2668

7.6.

Chronic Kidney Disease2668

7.7.

Women2668

7.8.

Anemia, Bleeding, and Transfusion2668

7.9.

Cocaine and Methamphetamine Users2668

7.10.

Vasospastic (Prinzmetal) Angina2668

7.11.

ACS With Angiographically Normal Coronary Arteries2669

7.12.

Stress (Takotsubo) Cardiomyopathy2669

8.

Quality of Care and Outcomes for ACS—Use of Performance Measures and Registries: Recommendation2669

9.

Summary and Evidence Gaps2669

References2670

Appendix 1

  • Author Relationships With Industry and Other Entities (Relevant)2680

Appendix 2

  • Reviewer Relationships With Industry and Other Entities (Relevant)2683

Preamble

The American College of Cardiology (ACC) and the American Heart Association (AHA) are committed to the prevention and management of cardiovascular diseases through professional education and research for clinicians, providers, and patients. Since 1980, the ACC and AHA have shared a responsibility to translate scientific evidence into clinical practice guidelines (CPGs) with recommendations to standardize and improve cardiovascular health. These CPGs, based on systematic methods to evaluate and classify evidence, provide a cornerstone of quality cardiovascular care.

In response to published reports from the Institute of Medicine (1,2) and the ACC/AHA’s mandate to evaluate new knowledge and maintain relevance at the point of care, the ACC/AHA Task Force on Practice Guidelines (Task Force) began modifying its methodology. This modernization effort is published in the 2012 Methodology Summit Report (3) and 2014 perspective article (4). The latter recounts the history of the collaboration, changes over time, current policies, and planned initiatives to meet the needs of an evolving healthcare environment. Recommendations on value in proportion to resource utilization will be incorporated as high-quality comparative-effectiveness data become available (5). The relationships between CPGs and data standards, appropriate use criteria, and performance measures are addressed elsewhere (4).

Intended Use—CPGs provide recommendations applicable to patients with or at risk of developing cardiovascular disease. The focus is on medical practice in the United States, but CPGs developed in collaboration with other organizations may have a broader target. Although CPGs may be used to inform regulatory or payer decisions, the intent is to improve the quality of care and be aligned with the patient's best interest.

Evidence Review—Guideline writing committee (GWC) members are charged with reviewing the literature; weighing the strength and quality of evidence for or against particular tests, treatments, or procedures; and estimating expected health outcomes when data exist. In analyzing the data and developing CPGs, the GWC uses evidence-based methodologies developed by the Task Force (6). A key component of the ACC/AHA CPG methodology is the development of recommendations on the basis of all available evidence. Literature searches focus on randomized controlled trials (RCTs) but also include registries, nonrandomized comparative and descriptive studies, case series, cohort studies, systematic reviews, and expert opinion. Only selected references are cited in the CPG. To ensure that CPGs remain current, new data are reviewed biannually by the GWCs and the Task Force to determine if recommendations should be updated or modified. In general, a target cycle of 5 years is planned for full revisions (1).

Guideline-Directed Medical Therapy—Recognizing advances in medical therapy across the spectrum of cardiovascular diseases, the Task Force designated the term “guideline-directed medical therapy” (GDMT) to represent recommended medical therapy as defined mainly by Class I measures, generally a combination of lifestyle modification and drug- and device-based therapeutics. As medical science advances, GDMT evolves, and hence GDMT is preferred to “optimal medical therapy.” For GDMT and all other recommended drug treatment regimens, the reader should confirm the dosage with product insert material and carefully evaluate for contraindications and possible drug interactions. Recommendations are limited to treatments, drugs, and devices approved for clinical use in the United States.

Class of Recommendation and Level of Evidence—Once recommendations are written, the Class of Recommendation (COR; i.e., the strength the GWC assigns to the recommendation, which encompasses the anticipated magnitude and judged certainty of benefit in proportion to risk) is assigned by the GWC. Concurrently, the Level of Evidence (LOE) rates the scientific evidence supporting the effect of the intervention on the basis on the type, quality, quantity, and consistency of data from clinical trials and other reports (Table 1) (4). Unless otherwise stated, recommendations are presented in order by the COR and then the LOE. Where comparative data exist, preferred strategies take precedence. When more than 1 drug, strategy, or therapy exists within the same COR and LOE and there are no comparative data, options are listed alphabetically.

Table 1. Applying Classification of Recommendations and Level of Evidence

A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the clinical practice guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.

*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes mellitus, history of prior myocardial infarction, history of heart failure, and prior aspirin use.

†For comparative-effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated.

Relationships With Industry and Other Entities—The ACC and AHA exclusively sponsor the work of GWCs without commercial support, and members volunteer their time for this activity. The Task Force makes every effort to avoid actual, potential, or perceived conflicts of interest that might arise through relationships with industry or other entities (RWI). All GWC members and reviewers are required to fully disclose current industry relationships or personal interests from 12 months before initiation of the writing effort. Management of RWI involves selecting a balanced GWC and requires that both the chair and a majority of GWC members have no relevant RWI (see Appendix 1 for the definition of relevance). GWC members are restricted with regard to writing or voting on sections to which their RWI apply. In addition, for transparency, GWC members’ comprehensive disclosure information is available as an  online supplement. Comprehensive disclosure information for the Task Force is available as an additional supplement. The Task Force strives to avoid bias by selecting experts from a broad array of backgrounds representing different geographic regions, sexes, ethnicities, races, intellectual perspectives/biases, and scopes of clinical practice. Selected organizations and professional societies with related interests and expertise are invited to participate as partners or collaborators.

Individualizing Care in Patients With Associated Conditions and Comorbidities—The ACC and AHA recognize the complexity of managing patients with multiple conditions, compared with managing patients with a single disease, and the challenge is compounded when CPGs for evaluation or treatment of several coexisting illnesses are discordant or interacting (7). CPGs attempt to define practices that meet the needs of patients in most, but not all, circumstances and do not replace clinical judgment.

Clinical Implementation—Management in accordance with CPG recommendations is effective only when followed; therefore, to enhance their commitment to treatment and compliance with lifestyle adjustment, clinicians should engage the patient to participate in selecting interventions on the basis of the patient’s individual values and preferences, taking associated conditions and comorbidities into consideration (e.g., shared decision making). Consequently, there are circumstances in which deviations from these guidelines are appropriate.

The recommendations in this CPG are the official policy of the ACC and AHA until they are superseded by a published addendum, focused update, or revised full-text CPG. The reader is encouraged to consult the full-text CPG (8) for additional guidance and details about the management of patients with non–ST-elevation acute coronary syndrome (NSTE-ACS) because the executive summary contains mainly the recommendations.

Jeffrey L. Anderson, MD, FACC, FAHA

Chair, ACC/AHA Task Force on Practice Guidelines

1 Introduction

1.1 Methodology and Evidence Review

The recommendations listed in this CPG are, whenever possible, evidence based. An extensive evidence review was conducted through October 2012, and other selected references published through April 2014 were reviewed by the GWC. Literature included was derived from research involving human subjects, published in English, and indexed in MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality Reports, and other selected databases relevant to this CPG. The relevant data are included in evidence tables in the Online Data Supplement. Key search words included but were not limited to the following: acute coronary syndrome, anticoagulant therapy, antihypertensives, anti-ischemic therapy, antiplatelet therapy, antithrombotic therapy, beta blockers, biomarkers, calcium channel blockers, cardiac rehabilitation, conservative management, diabetes mellitus, glycoprotein IIb/IIIa inhibitors, heart failure, invasive strategy, lifestyle modification, myocardial infarction, nitrates, non-ST-elevation, P2Y12receptor inhibitor, percutaneous coronary intervention, renin-angiotensin-aldosterone inhibitors, secondary prevention, smoking cessation, statins, stent, thienopyridines, troponins, unstable angina, and weight management. Additionally, the GWC reviewed documents related to NSTE-ACS previously published by the ACC and AHA. References selected and published in this document are representative and not all-inclusive.

1.2 Organization of the GWC

The GWC was composed of clinicians, cardiologists, internists, interventionists, surgeons, emergency medicine specialists, family practitioners, and geriatricians. The GWC included representatives from the ACC and AHA, American Academy of Family Physicians, American College of Emergency Physicians, American College of Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

1.3 Document Review and Approval

This document was reviewed by 2 official reviewers each nominated by the ACC and AHA; 1 reviewer each from the American Academy of Family Physicians, American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons; and 37 individual content reviewers (including members of the American Association of Clinical Chemistry, ACC Heart Failure and Transplant Section Leadership Council, ACC Cardiovascular Imaging Section Leadership Council, ACC Interventional Section Leadership Council, ACC Prevention of Cardiovascular Disease Committee, ACC Surgeons’ Council, Association of International Governors, and Department of Health and Human Services). Reviewers’ RWI information was distributed to the GWC and is published in this document (Appendix 2).

This document was approved for publication by the governing bodies of the ACC and the AHA and endorsed by the American Association for Clinical Chemistry, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons.

1.4 Scope of the CPG

The 2014 NSTE-ACS CPG is a full revision of the 2007 ACCF/AHA CPG for the management of patients with unstable angina (UA) and non–ST-elevation myocardial infarction (NSTEMI) and the 2012 focused update (9). The new title, “Non–ST-Elevation Acute Coronary Syndromes,” emphasizes the continuum between UA and NSTEMI. At presentation, patients with UA and NSTEMI can be indistinguishable and are therefore considered together in this CPG.

In the United States, NSTE-ACS affects >625,000 patients annually,

Estimate includes secondary discharge diagnoses.

or almost three fourths of all patients with acute coronary syndrome (ACS) (10). In selecting the initial approach to care, the term “ischemia-guided strategy” has replaced the previous descriptor, “initial conservative management,” to more clearly convey the physiological rationale of this approach.

The task of the 2014 GWC was to establish a contemporary CPG for the optimal management of patients with NSTE-ACS. It incorporates both established and new evidence from published clinical trials, as well as information from basic science and comprehensive review articles. These recommendations were developed to guide the clinician in improving outcomes for patients with NSTE-ACS. Table 2 lists documents deemed pertinent to this effort and is intended for use as a resource, thus obviating the need to repeat extant CPG recommendations.

Table 2. Associated CPGs and Statements

TitleOrganizationPublication Year (Reference)
CPGs
Stable ischemic heart diseaseACC/AHA/AATS/PCNA/SCAI/STS2014 (11) 2012 (12)
Atrial fibrillationAHA/ACC/HRS2014 (13)
Assessment of cardiovascular riskACC/AHA2013 (14)
Heart failureACC/AHA2013 (15)
Lifestyle management to reduce cardiovascular riskAHA/ACC2013 (16)
Management of overweight and obesity in adultsAHA/ACC/TOS2013 (17)
ST-elevation myocardial infarctionACC/AHA2013 (18)
Treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adultsACC/AHA2013 (19)
Acute myocardial infarction in patients presenting with ST-segment elevationESC2012 (20)
Device-based therapyACC/AHA/HRS2013 (21)
Third universal definition of myocardial infarctionESC/ACC/AHA/WHF2012 (22)
Acute coronary syndromes in patients presenting without persistent ST-segment elevationESC2011 (23)
Coronary artery bypass graft surgeryACC/AHA2011 (24)
Hypertrophic cardiomyopathyACC/AHA2011 (25)
Effectiveness-based guidelines for the prevention of cardiovascular disease in womenAHA/ACC2011 (26)
Percutaneous coronary interventionACC/AHA/SCAI2011 (27)
Secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular diseaseAHA/ACC2011 (28)
Assessment of cardiovascular risk in asymptomatic adultsACC/AHA2010 (29)
Myocardial revascularizationESC2010 (30)
Unstable angina and non–ST-elevation myocardial infarctionNICE2010 (31)
Guidelines for cardiopulmonary resuscitation and emergency cardiovascular care—part 9: postcardiac arrest careAHA2010 (32)
Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressureNHLBI2003 (33)
Statements
Key data elements and definitions for measuring the clinical management and outcomes of patients with acute coronary syndromes and coronary artery diseaseACC/AHA2013 (34)
Practical clinical considerations in the interpretation of troponin elevationsACC2012 (35)
Testing of low-risk patients presenting to the emergency department with chest painAHA2010 (36)
Primary prevention of cardiovascular diseases in people with diabetes mellitusAHA/ADA2007 (37)
Prevention and control of influenzaCDC2005 (38)

AATS indicates American Association for Thoracic Surgery; ACC, American College of Cardiology; ADA, American Diabetes Association; AHA, American Heart Association; CDC, Centers for Disease Control and Prevention; CPG, clinical practice guideline; ESC, European Society of Cardiology; HRS, Heart Rhythm Society; NHLBI, National Heart, Lung, and Blood Institute; NICE, National Institute for Health and Clinical Excellence; PCNA, Preventive Cardiovascular Nurses Association; SCAI, Society for Cardiovascular Angiography and Interventions; SIHD, stable ischemic heart disease; STS, Society of Thoracic Surgeons; TOS, The Obesity Society; and WHF, World Heart Federation.

∗ The full-text SIHD CPG is from 2012 (12). A focused update was published in 2014 (11).

† Minor modifications were made in 2013. For a full explanation of the changes, see http://publications.nice.org.uk/unstable-angina-and-nstemi-cg94/changes-after-publication.

The GWC abbreviated the discussion sections to include an explanation of salient information related to the recommendations. In contrast to textbook declaratory presentations, explanations were supplemented with evidence tables. The GWC also provided a brief summary of the relevant recommendations and references related to secondary prevention rather than detailed reiteration. Throughout, the goal was to provide the clinician with concise, evidence-based contemporary recommendations and the supporting documentation to encourage their application.

2 Overview of ACS

ACS has evolved as a useful operational term that refers to a spectrum of conditions compatible with acute myocardial ischemia and/or infarction that are usually due to an abrupt reduction in coronary blood flow (Figure 1).

Figure 1.
Figure 1.

Acute Coronary Syndromes

The top half of the figure illustrates the progression of plaque formation and onset and complications of NSTE-ACS, with management at each stage. The numbered section of an artery depicts the process of atherogenesis from 1) normal artery to 2) extracellular lipid in the subintima to 3) fibrofatty stage to 4) procoagulant expression and weakening of the fibrous cap. ACS develops with 5) disruption of the fibrous cap, which is the stimulus for thrombogenesis. 6) Thrombus resorption may be followed by collagen accumulation and smooth muscle cell growth. Thrombus formation and possible coronary vasospasm reduce blood flow in the affected coronary artery and cause ischemic chest pain.

The bottom half of the figure illustrates the clinical, pathological, electrocardiographic, and biomarker correlates in ACS and the general approach to management. Flow reduction may be related to a completely occlusive thrombus (bottom half, right side) or subtotally occlusive thrombus (bottom half, left side). Most patients with ST-elevation (thick white arrow in bottom panel) develop QwMI, and a few (thin white arrow) develop NQMI. Those without ST-elevation have either UA or NSTEMI (thick red arrows), a distinction based on cardiac biomarkers. Most patients presenting with NSTEMI develop NQMI; a few may develop QwMI. The spectrum of clinical presentations including UA, NSTEMI, and STEMI is referred to as ACS. This NSTE-ACS CPG includes sections on initial management before NSTE-ACS, at the onset of NSTE-ACS, and during the hospital phase. Secondary prevention and plans for long-term management begin early during the hospital phase. Patients with noncardiac etiologies make up the largest group presenting to the ED with chest pain (dashed arrow).

*Elevated cardiac biomarker (e.g., troponin), Section 3.4.

ACS indicates acute coronary syndrome; CPG, clinical practice guideline; Dx, diagnosis; ECG, electrocardiogram; ED, emergency department; MI, myocardial infarction; NQMI, non–Q-wave myocardial infarction; NSTE-ACS, non–ST-elevation acute coronary syndromes; NSTEMI, non–ST-elevation myocardial infarction; QwMI, Q-wave myocardial infarction; STEMI, ST-elevation myocardial infarction; and UA, unstable angina.

3 Initial Evaluation and Management: Recommendations

3.1 Clinical Assessment and Initial Evaluation

Class I

1.

Patients with suspected ACS should be risk stratified based on the likelihood of ACS and adverse outcome(s) to decide on the need for hospitalization and assist in the selection of treatment options (40–42). (Level of Evidence: B)

3.2 Emergency Department or Outpatient Facility Presentation

Class I

1.

Patients with suspected ACS and high-risk features such as continuing chest pain, severe dyspnea, syncope/presyncope, or palpitations should be referred immediately to the emergency department (ED) and transported by emergency medical services when available. (Level of Evidence: C)

Class IIb

1.

Patients with less severe symptoms may be considered for referral to the ED, a chest pain unit, or a facility capable of performing adequate evaluation depending on clinical circumstances. (Level of Evidence: C)

3.3 Prognosis—Early Risk Stratification

See Figure 2 and Table 3 for estimation at presentation of death and nonfatal cardiac ischemic events. See Table 4 for a summary of recommendations from this section.

Class I

1.

In patients with chest pain or other symptoms suggestive of ACS, a 12-lead electrocardiogram (ECG) should be performed and evaluated for ischemic changes within 10 minutes of the patient’s arrival at an emergency facility (22). (Level of Evidence: C)

2.

If the initial ECG is not diagnostic but the patient remains symptomatic and there is a high clinical suspicion for ACS, serial ECGs (e.g., 15- to 30-minute intervals during the first hour) should be performed to detect ischemic changes. (Level of Evidence: C)

3.

Serial cardiac troponin I or T levels (when a contemporary assay is used) should be obtained at presentation and 3 to 6 hours after symptom onset (see Section 3.4.1, Class I, #3 recommendation if time of symptom onset is unclear) in all patients who present with symptoms consistent with ACS to identify a rising and/or falling pattern of values (22,43–48). (Level of Evidence: A)

4.

Additional troponin levels should be obtained beyond 6 hours after symptom onset (see Section 3.4.1, Class I, #3 recommendation if time of symptom onset is unclear) in patients with normal troponin levels on serial examination when changes on ECG and/or clinical presentation confer an intermediate or high index of suspicion for ACS (22,49–51). (Level of Evidence: A)

5.

Risk scores should be used to assess prognosis in patients with NSTE-ACS (40–42,52–57). (Level of Evidence: A)

Class IIa

1.

Risk-stratification models can be useful in management (40–42,52–58). (Level of Evidence: B)

2.

It is reasonable to obtain supplemental electrocardiographic leads V7 to V9 in patients whose initial ECG is nondiagnostic and who are at intermediate/high risk of ACS (59–61). (Level of Evidence: B)

Class IIb

1.

Continuous monitoring with 12-lead ECG may be a reasonable alternative in patients whose initial ECG is nondiagnostic and who are at intermediate/high risk of ACS (62,63). (Level of Evidence: B)

2.

Measurement of B-type natriuretic peptide or N-terminal pro–B-type natriuretic peptide may be considered to assess risk in patients with suspected ACS (64–68). (Level of Evidence: B)

Figure 2.
Figure 2.

Global Registry of Acute Coronary Events Risk Calculator for In-Hospital Mortality for Acute Coronary Syndrome

Table 3. TIMI Risk Score for NSTE-ACS

TIMI Risk ScoreAll-Cause Mortality, New or Recurrent MI, or Severe Recurrent Ischemia Requiring Urgent Revascularization Through 14 d After Randomization, %
014.7
28.3
313.2
419.9
526.2
6–740.9

CAD indicates coronary artery disease; ECG, electrocardiogram; MI, myocardial infarction; NSTE-ACS, non–ST-elevation acute coronary syndromes; and TIMI, Thrombolysis In Myocardial Infarction.

∗ The TIMI risk score is determined by the sum of the presence of 7 variables at admission; 1 point is given for each of the following variables: ≥65 y of age; ≥3 risk factors for CAD; prior coronary stenosis ≥50%; ST deviation on ECG; ≥2 anginal events in prior 24 h; use of aspirin in prior 7 d; and elevated cardiac biomarkers.

Table 4. Summary of Recommendations for Prognosis: Early Risk Stratification

RecommendationsCORLOEReferences
Perform rapid determination of likelihood of ACS, including a 12-lead ECG within 10 min of arrival at an emergency facility, in patients whose symptoms suggest ACSIC(22)
Perform serial ECGs at 15- to 30-min intervals during the first hour in symptomatic patients with initial nondiagnostic ECGICN/A
Measure cardiac troponin (cTnI or cTnT) in all patients with symptoms consistent with ACSIA(22,43–48)
Measure serial cardiac troponin I or T at presentation and 3–6 h after symptom onset in all patients with symptoms consistent with ACSIA(22,49–51)
Use risk scores to assess prognosis in patients with NSTE-ACSIA(40–42,52–57)
Risk-stratification models can be useful in managementIIaB(40–42,52–58)
Obtain supplemental electrocardiographic leads V7 to V9 in patients with initial nondiagnostic ECG at intermediate/high risk for ACSIIaB(59–61)
Continuous monitoring with 12-lead ECG may be a reasonable alternative with initial nondiagnostic ECG in patients at intermediate/high risk for ACSIIbB(62,63)
BNP or NT–pro-BNP may be considered to assess risk in patients with suspected ACSIIbB(64–68)

ACS indicates acute coronary syndromes; BNP, B-type natriuretic peptide; COR, Class of Recommendation; cTnI, cardiac troponin I; cTnT, cardiac troponin T; ECG, electrocardiogram; LOE, Level of Evidence; N/A, not available; NSTE-ACS, non−ST-elevation acute coronary syndromes; and NT–pro-BNP, N-terminal pro–B-type natriuretic peptide.

∗ See Section 3.4.1, Class I, #3 recommendation if time of symptom onset is unclear.

3.4 Cardiac Biomarkers and the Universal Definition of Myocardial Infarction

See Table 5 for a summary of recommendations from this section.

Table 5. Summary of Recommendations for Cardiac Biomarkers and the Universal Definition of MI

RecommendationsCORLOEReferences
Diagnosis
Measure cardiac-specific troponin (troponin I or T) at presentation and 3—6 h after symptom onset in all patients with suspected ACS to identify pattern of valuesIA(22,43–48,70–74)
Obtain additional troponin levels beyond 6 h in patients with initial normal serial troponins with electrocardiographic changes and/or intermediate/high risk clinical featuresIA(22,49–51,75)
Consider time of presentation the time of onset with ambiguous symptom onset for assessing troponin valuesIA(44,45,49)
With contemporary troponin assays, CK-MB and myoglobin are not useful for diagnosis of ACSIII: No BenefitA(76–82)
Prognosis
Troponin elevations are useful for short- and long-term prognosisIB(48,50,83,84)
Remeasurement of troponin value once on d 3 or 4 in patients with MI may be reasonable as an index of infarct size and dynamics of necrosisIIbB(82,83)
BNP may be reasonable for additional prognostic informationIIbB(64,65,85–89)

ACS indicates acute coronary syndromes; BNP, B-type natriuretic peptide; CK-MB, creatine kinase myocardial isoenzyme; COR, Class of Recommendation; LOE, Level of Evidence; and MI, myocardial infarction.

3.4.1 Biomarkers: Diagnosis

Class I

1.

Cardiac-specific troponin (troponin I or T when a contemporary assay is used) levels should be measured at presentation and 3 to 6 hours after symptom onset in all patients who present with symptoms consistent with ACS to identify a rising and/or falling pattern (22,43–48,70–74). (Level of Evidence: A)

2.

Additional troponin levels should be obtained beyond 6 hours after symptom onset in patients with normal troponins on serial examination when electrocardiographic changes and/or clinical presentation confer an intermediate or high index of suspicion for ACS (22,49–51,75). (Level of Evidence: A)

3.

If the time of symptom onset is ambiguous, the time of presentation should be considered the time of onset for assessing troponin values (44,45,49). (Level of Evidence: A)

Class III: No Benefit

1.

With contemporary troponin assays, creatine kinase myocardial isoenzyme (CK-MB) and myoglobin are not useful for diagnosis of ACS (76–82). (Level of Evidence: A)

3.4.2 Biomarkers: Prognosis

Class I

1.

The presence and magnitude of troponin elevations are useful for short- and long-term prognosis (48,50,83,84). (Level of Evidence: B)

Class IIb

1.

It may be reasonable to remeasure troponin once on day 3 or day 4 in patients with a myocardial infarction (MI) as an index of infarct size and dynamics of necrosis (82,83). (Level of Evidence: B)

2.

Use of selected newer biomarkers, especially B-type natriuretic peptide, may be reasonable to provide additional prognostic information (64,65,85–89). (Level of Evidence: B)

3.5 Discharge From the ED or Chest Pain Unit

Class IIa

1.

It is reasonable to observe patients with symptoms consistent with ACS without objective evidence of myocardial ischemia (nonischemic initial ECG and normal cardiac troponin) in a chest pain unit or telemetry unit with serial ECGs and cardiac troponin at 3- to 6-hour intervals (90–94). (Level of Evidence: B)

2.

It is reasonable for patients with possible ACS who have normal serial ECGs and cardiac troponins to have a treadmill ECG (93–95)(Level of Evidence: A), stress myocardial perfusion imaging (93), or stress echocardiography (96,97) before discharge or within 72 hours after discharge. (Level of Evidence: B)

3.

In patients with possible ACS and a normal ECG, normal cardiac troponins, and no history of coronary artery disease (CAD), it is reasonable to initially perform (without serial ECGs and troponins) coronary computed tomography angiography to assess coronary artery anatomy (98–100)(Level of Evidence: A) or rest myocardial perfusion imaging with a technetium-99m radiopharmaceutical to exclude myocardial ischemia (101,102). (Level of Evidence: B)

4.

It is reasonable to give low-risk patients who are referred for outpatient testing daily aspirin, short-acting nitroglycerin, and other medication if appropriate (e.g., beta blockers), with instructions about activity level and clinician follow-up. (Level of Evidence: C)

4 Early Hospital Care: Recommendations

See Table 6 for a summary of recommendations from this section.

Table 6. Summary of Recommendations for Early Hospital Care

RecommendationsCORLOEReferences
Oxygen
Administer supplemental oxygen only with oxygen saturation <90%, respiratory distress, or other high-risk features for hypoxemiaICN/A
Nitrates
Administer sublingual NTG every 5 min × 3 for continuing ischemic pain and then assess need for IV NTGIC(103–105)
Administer IV NTG for persistent ischemia, HF, or hypertensionIB(106–111)
Nitrates are contraindicated with recent use of a phosphodiesterase inhibitorIII: HarmB(112–114)
Analgesic therapy
IV morphine sulfate may be reasonable for continued ischemic chest pain despite maximally tolerated anti-ischemic medicationsIIbB(115,116)
NSAIDs (except aspirin) should not be initiated and should be discontinued during hospitalization for NSTE-ACS because of the increased risk of MACE associated with their useIII: HarmB(117,118)
Beta-adrenergic blockers
Initiate oral beta blockers within the first 24 h in the absence of HF, low-output state, risk for cardiogenic shock, or other contraindications to beta blockadeIA(119–121)
Use of sustained-release metoprolol succinate, carvedilol, or bisoprolol is recommended for beta-blocker therapy with concomitant NSTE-ACS, stabilized HF, and reduced systolic functionICN/A
Re-evaluate to determine subsequent eligibility in patients with initial contraindications to beta blockersICN/A
It is reasonable to continue beta-blocker therapy in patients with normal LV function with NSTE-ACSIIaC(120,122)
IV beta blockers are potentially harmful when risk factors for shock are presentIII: HarmB(123)
CCBs
Administer initial therapy with nondihydropyridine CCBs with recurrent ischemia and contraindications to beta blockers in the absence of LV dysfunction, increased risk for cardiogenic shock, PR interval >0.24 s, or second- or third-degree atrioventricular block without a cardiac pacemakerIB(124–126)
Administer oral nondihydropyridine calcium antagonists with recurrent ischemia after use of beta blocker and nitrates in the absence of contraindicationsICN/A
CCBs are recommended for ischemic symptoms when beta blockers are not successful, are contraindicated, or cause unacceptable side effectsICN/A
Long-acting CCBs and nitrates are recommended for patients with coronary artery spasmICN/A
Immediate-release nifedipine is contraindicated in the absence of a beta blockerIII: HarmB(127,128)
Cholesterol management
Initiate or continue high-intensity statin therapy in patients with no contraindicationsIA(129–133)
Obtain a fasting lipid profile, preferably within 24 hIIaCN/A

CCB indicates calcium channel blocker; COR, Class of Recommendation; HF, heart failure; IV, intravenous; LOE, Level of Evidence; LV, left ventricular; MACE, major adverse cardiac event; N/A, not available; NSAIDs, nonsteroidal anti-inflammatory drugs; NSTE-ACS, non–ST-elevation acute coronary syndromes; and NTG, nitroglycerin.

∗ Short-acting dihydropyridine calcium channel antagonists should be avoided.

4.1 Standard Medical Therapies

4.1.1 Oxygen

Class I

1.

Supplemental oxygen should be administered to patients with NSTE-ACS with arterial oxygen saturation less than 90%, respiratory distress, or other high-risk features of hypoxemia. (Level of Evidence: C)

4.1.2 Nitrates

Class I

1.

Patients with NSTE-ACS with continuing ischemic pain should receive sublingual nitroglycerin (0.3 mg–0.4 mg) every 5 minutes for up to 3 doses, after which an assessment should be made about the need for intravenous nitroglycerin if not contraindicated (103–105). (Level of Evidence: C)

2.

Intravenous nitroglycerin is indicated for patients with NSTE-ACS for the treatment of persistent ischemia, heart failure (HF), or hypertension (106–111). (Level of Evidence: B)

Class III: Harm

1.

Nitrates should not be administered to patients with NSTE-ACS who recently received a phosphodiesterase inhibitor, especially within 24 hours of sildenafil or vardenafil, or within 48 hours of tadalafil (112–114). (Level of Evidence: B)

4.1.3 Analgesic Therapy

Class IIb

1.

In the absence of contraindications, it may be reasonable to administer morphine sulfate intravenously to patients with NSTE-ACS if there is continued ischemic chest pain despite treatment with maximally tolerated anti-ischemic medications (115,116). (Level of Evidence: B)

Class III: Harm

1.

Nonsteroidal anti-inflammatory drugs (NSAIDs) (except aspirin) should not be initiated and should be discontinued during hospitalization for NSTE-ACS because of the increased risk of MACE associated with their use (117,118). (Level of Evidence: B)

4.1.4 Beta-Adrenergic Blockers

Class I

1.

Oral beta-blocker therapy should be initiated within the first 24 hours in patients who do not have any of the following: 1) signs of HF, 2) evidence of low-output state, 3) increased risk for cardiogenic shock, or 4) other contraindications to beta blockade (e.g., PR interval >0.24 second, second- or third-degree heart block without a cardiac pacemaker, active asthma, or reactive airway disease) (119–121). (Level of Evidence: A)

2.

In patients with concomitant NSTE-ACS, stabilized HF, and reduced systolic function, it is recommended to continue beta-blocker therapy with 1 of the 3 drugs proven to reduce mortality in patients with HF: sustained-release metoprolol succinate, carvedilol, or bisoprolol. (Level of Evidence: C)

3.

Patients with documented contraindications to beta blockers in the first 24 hours of NSTE-ACS should be reevaluated to determine their subsequent eligibility. (Level of Evidence: C)

Class IIa

1.

It is reasonable to continue beta-blocker therapy in patients with normal left ventricular (LV) function with NSTE-ACS (120,122). (Level of Evidence: C)

Class III: Harm

1.

Administration of intravenous beta blockers is potentially harmful in patients with NSTE-ACS who have risk factors for shock (123). (Level of Evidence: B)

4.1.5 Calcium Channel Blockers

Class I

1.

In patients with NSTE-ACS, continuing or frequently recurring ischemia, and a contraindication to beta blockers, a nondihydropyridine calcium channel blocker (CCB) (e.g., verapamil or diltiazem) should be given as initial therapy in the absence of clinically significant LV dysfunction, increased risk for cardiogenic shock, PR interval greater than 0.24 second, or second- or third-degree atrioventricular block without a cardiac pacemaker (124–126). (Level of Evidence: B)

2.

Oral nondihydropyridine calcium antagonists are recommended in patients with NSTE-ACS who have recurrent ischemia in the absence of contraindications, after appropriate use of beta blockers and nitrates. (Level of Evidence: C)

3.

CCBs

Short-acting dihydropyridine calcium channel antagonists should be avoided.

are recommended for ischemic symptoms when beta blockers are not successful, are contraindicated, or cause unacceptable side effects. (Level of Evidence: C)

4.

Long-acting CCBs and nitrates are recommended in patients with coronary artery spasm. (Level of Evidence: C)

Class III: Harm

1.

Immediate-release nifedipine should not be administered to patients with NSTE-ACS in the absence of beta-blocker therapy (127,128). (Level of Evidence: B)

4.1.6 Cholesterol Management

Class I

1.

High-intensity statin therapy should be initiated or continued in all patients with NSTE-ACS and no contraindications to its use (129–133). (Level of Evidence: A)

Class IIa

1.

It is reasonable to obtain a fasting lipid profile in patients with NSTE-ACS, preferably within 24 hours of presentation. (Level of Evidence: C)

4.2 Inhibitors of the Renin-Angiotensin-Aldosterone System

Class I

1.

Angiotensin-converting enzyme (ACE) inhibitors should be started and continued indefinitely in all patients with left ventricular ejection fraction (LVEF) less than 0.40 and in those with hypertension, diabetes mellitus, or stable chronic kidney disease (CKD) (Section 7.6), unless contraindicated (134,135). (Level of Evidence: A)

2.

Angiotensin receptor blockers are recommended in patients with HF or MI with LVEF less than 0.40 who are ACE inhibitor intolerant (136,137). (Level of Evidence: A)

3.

Aldosterone blockade is recommended in post–MI patients who are without significant renal dysfunction (creatinine >2.5 mg/dL in men or >2.0 mg/dL in women) or hyperkalemia (K+ >5.0 mEq/L) who are receiving therapeutic doses of ACE inhibitor and beta blocker and have a LVEF 0.40 or less, diabetes mellitus, or HF (138). (Level of Evidence: A)

Class IIa

1.

Angiotensin receptor blockers are reasonable in other patients with cardiac or other vascular disease who are ACE inhibitor intolerant (139). (Level of Evidence: B)

Class IIb

1.

ACE inhibitors may be reasonable in all other patients with cardiac or other vascular disease (140,141). (Level of Evidence: B)

4.3 Initial Antiplatelet/Anticoagulant Therapy in Patients With Definite or Likely NSTE-ACS

4.3.1 Initial Oral and Intravenous Antiplatelet Therapy in Patients With Definite or Likely NSTE-ACS Treated With an Initial Invasive or Ischemia-Guided Strategy

See Table 7 for a summary of recommendations from this section.

Class I

1.

Non–enteric-coated, chewable aspirin (162 mg to 325 mg) should be given to all patients with NSTE-ACS without contraindications as soon as possible after presentation, and a maintenance dose of aspirin (81 mg/d to 325 mg/d) should be continued indefinitely (142–144,147,363). (Level of Evidence: A)

See Section 5.1 for recommendations at the time of PCI.

2.

In patients with NSTE-ACS who are unable to take aspirin because of hypersensitivity or major gastrointestinal intolerance, a loading dose of clopidogrel followed by a daily maintenance dose should be administered (145). (Level of Evidence: B)

3.

A P2Y12 inhibitor (either clopidogrel or ticagrelor) in addition to aspirin should be administered for up to 12 months to all patients with NSTE-ACS without contraindications who are treated with either an early invasive§

See Section 4.3.1.2 in the full-text CPG for prasugrel indications in either an early invasive or ischemia-guided strategy.

or ischemia-guided strategy. Options include:

Clopidogrel: 300-mg or 600-mg loading dose, then 75 mg daily (143,146)(Level of Evidence: B)

Ticagrelor

The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily (144).

: 180-mg loading dose, then 90 mg twice daily (147,148)(Level of Evidence: B)

Class IIa

1.

It is reasonable to use ticagrelor in preference to clopidogrel for P2Y12 treatment in patients with NSTE-ACS who undergo an early invasive or ischemia-guided strategy (147,148). (Level of Evidence: B)

Class IIb

1.

In patients with NSTE-ACS treated with an early invasive strategy and dual antiplatelet therapy (DAPT) with intermediate/high-risk features (e.g., positive troponin), a glycoprotein (GP) IIb/IIIa inhibitor may be considered as part of initial antiplatelet therapy. Preferred options are eptifibatide or tirofiban (41,149,150). (Level of Evidence: B)

Table 7. Summary of Recommendations for Initial Antiplatelet/Anticoagulant Therapy in Patients With Definite or Likely NSTE-ACS and PCI

RecommendationsDosing and Special ConsiderationsCORLOEReferences
Aspirin
Non–enteric-coated aspirin to all patients promptly after presentation162 mg–325 mgIA(142–144)
Aspirin maintenance dose continued indefinitely81 mg/d–325 mg/dIA(142–144,147,363)
P2Y12inhibitors
Clopidogrel loading dose followed by daily maintenance dose in patients unable to take aspirin75 mgIB(145)
  • P2Y12 inhibitor, in addition to aspirin, for up to 12 mo for patients treated initially with either an early invasive or initial ischemia-guided strategy:

    Clopidogrel

    Ticagrelor

IB
300-mg or 600-mg loading dose, then 75 mg/d(143,146)
180-mg loading dose, then 90 mg BID(147,148)
P2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor) continued for at least 12 mo in post–PCI patients treated with coronary stentsN/AIB(147,169–172)
Ticagrelor in preference to clopidogrel for patients treated with an early invasive or ischemia-guided strategyN/AIIaB(147,148)
GP IIb/IIIa inhibitors
GP IIb/IIIa inhibitor in patients treated with an early invasive strategy and DAPT with intermediate/high-risk features (e.g., positive troponin)

Preferred options are eptifibatide or tirofiban

IIbB(41,149,150)
Parenteral anticoagulant and fibrinolytic therapy
SC enoxaparin for duration of hospitalization or until PCI is performed

1 mg/kg SC every 12 h (reduce dose to 1 mg/kg/d SC in patients with CrCl <30 mL/min)

Initial 30 mg IV loading dose in selected patients

IA(151–153)
Bivalirudin until diagnostic angiography or PCI is performed in patients with early invasive strategy only

Loading dose 0.10 mg/kg loading dose followed by 0.25 mg/kg/h

Only provisional use of GP IIb/IIIa inhibitor in patients also treated with DAPT

IB(146,147,154,155)
SC fondaparinux for the duration of hospitalization or until PCI is performed

2.5 mg SC daily

IB(156–158)
Administer additional anticoagulant with anti-IIa activity if PCI is performed while patient is on fondaparinuxN/AIB(157–159)
IV UFH for 48 h or until PCI is performed

Initial loading dose 60 IU/kg (max 4,000 IU) with initial infusion 12 IU/kg/h (max 1,000 IU/h)

Adjusted to therapeutic aPTT range

IB(160–166)
IV fibrinolytic treatment not recommended in patients with NSTE-ACSN/AIII: HarmA(167,168)

See Section 5.1 for recommendations on antiplatelet/anticoagulant therapy at the time of PCI and Sections 6.2 and 6.3 for recommendations on posthospital therapy.

aPTT indicates activated partial thromboplastin time; BID, twice daily; COR, Class of Recommendation; CrCl, creatinine clearance; DAPT, dual antiplatelet therapy; GP, glycoprotein; IV, intravenous; LOE, Level of Evidence; max, maximum; N/A, not available; NSTE-ACS, non–ST-elevation acute coronary syndromes; PCI, percutaneous coronary intervention; SC, subcutaneous; and UFH, unfractionated heparin.

∗ The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily (144).

4.3.2 Initial Parenteral Anticoagulant Therapy in Patients With Definite NSTE-ACS

See Table 7 for a summary of recommendations from this section.

Class I

See Section 5.1 for recommendations at the time of PCI.

1.

In patients with NSTE-ACS, anticoagulation, in addition to antiplatelet therapy, is recommended for all patients irrespective of initial treatment strategy. Treatment options include:

Enoxaparin: 1 mg/kg subcutaneous (SC) every 12 hours (reduce dose to 1 mg/kg SC once daily in patients with creatinine clearance [CrCl] <30 mL/min), continued for the duration of hospitalization or until percutaneous coronary intervention (PCI) is performed. An initial intravenous loading dose of 30 mg has been used in selected patients (151–153). (Level of Evidence: A)

Bivalirudin: 0.10 mg/kg loading dose followed by 0.25 mg/kg per hour (only in patients managed with an early invasive strategy), continued until diagnostic angiography or PCI, with only provisional use of GP IIb/IIIa inhibitor, provided the patient is also treated with DAPT (146,147,154,155). (Level of Evidence: B)

Fondaparinux: 2.5 mg SC daily, continued for the duration of hospitalization or until PCI is performed (156–158). (Level of Evidence: B)

If PCI is performed while the patient is on fondaparinux, an additional anticoagulant with anti-IIa activity (either UFH or bivalirudin) should be administered because of the risk of catheter thrombosis (157–159). (Level of Evidence: B)

UFH IV: initial loading dose of 60 IU/kg (maximum 4,000 IU) with initial infusion of 12 IU/kg per hour (maximum 1,000 IU/h) adjusted per activated partial thromboplastin time to maintain therapeutic anticoagulation according to the specific hospital protocol, continued for 48 hours or until PCI is performed (160–166). (Level of Evidence: B)

Class III: Harm

1.

In patients with NSTE-ACS (i.e., without ST-elevation, true posterior MI, or left bundle-branch block not known to be old), intravenous fibrinolytic therapy should not be used (167,168). (Level of Evidence: A)

4.4 Ischemia-Guided Strategy Versus Early Invasive Strategies

See Figure 3 for the management algorithm for ischemia-guided versus early invasive strategy.

Figure 3.
Figure 3.

Algorithm for Management of Patients With Definite or Likely NSTE-ACS*

*See corresponding full-sentence recommendations and their explanatory footnotes.

†In patients who have been treated with fondaparinux (as upfront therapy) who are undergoing PCI, an additional anticoagulant with anti-IIa activity should be administered at the time of PCI because of the risk of catheter thrombosis.

ASA indicates aspirin; CABG, coronary artery bypass graft; cath, catheter; COR, Class of Recommendation; DAPT, dual antiplatelet therapy; GPI, glycoprotein IIb/IIIa inhibitor; LOE, Level of Evidence; NSTE-ACS, non–ST-elevation acute coronary syndrome; PCI, percutaneous coronary intervention; pts, patients; and UFH, unfractionated heparin.

4.4.1 Early Invasive and Ischemia-Guided Strategies

For definitions of invasive and ischemia-guided strategies, see Table 8.

Class I

1.

An urgent/immediate invasive strategy (diagnostic angiography with intent to perform revascularization if appropriate based on coronary anatomy) is indicated in patients (men and women

See Section 7.7 for additional information on women.

) with NSTE-ACS who have refractory angina or hemodynamic or electrical instability (without serious comorbidities or contraindications to such procedures) (40,42,173,174). (Level of Evidence: A)

2.

An early invasive strategy (diagnostic angiography with intent to perform revascularization if appropriate based on coronary anatomy) is indicated in initially stabilized patients with NSTE-ACS (without serious comorbidities or contraindications to such procedures) who have an elevated risk for clinical events (Table 8) (40,42,173–177). (Level of Evidence: B)

Class IIa

1.

It is reasonable to choose an early invasive strategy (within 24 hours of admission) over a delayed invasive strategy (within 24 to 72 hours) for initially stabilized high-risk patients with NSTE-ACS. For those not at high/intermediate risk, a delayed invasive approach is reasonable (173). (Level of Evidence: B)

Class IIb

1.

In initially stabilized patients, an ischemia-guided strategy may be considered for patients with NSTE-ACS (without serious comorbidities or contraindications to this approach) who have an elevated risk for clinical events (174,175,177). (Level of Evidence: B)

2.

The decision to implement an ischemia-guided strategy in initially stabilized patients (without serious comorbidities or contraindications to this approach) may be reasonable after considering clinician and patient preference. (Level of Evidence: C)

Class III: No Benefit

1.

An early invasive strategy (i.e., diagnostic angiography with intent to perform revascularization) is not recommended in patients with:

a.

Extensive comorbidities (e.g., hepatic, renal, pulmonary failure; cancer), in whom the risks of revascularization and comorbid conditions are likely to outweigh the benefits of revascularization. (Level of Evidence: C)

b.

Acute chest pain and a low likelihood of ACS who are troponin-negative (Level of Evidence: C), especially women (178). (Level of Evidence: B)

Table 8. Factors Associated With Appropriate Selection of Early Invasive Strategy or Ischemia-Guided Strategy in Patients With NSTE-ACS

Immediate invasive (within 2 h)Refractory angina
Signs or symptoms of HF or new or worsening mitral regurgitation
Hemodynamic instability
Recurrent angina or ischemia at rest or with low-level activities despite intensive medical therapy
Sustained VT or VF
Ischemia-guided strategyLow-risk score (e.g., TIMI [0 or 1], GRACE [<109])
Low-risk Tn-negative female patients
Patient or clinician preference in the absence of high-risk features
Early invasive (within 24 h)None of the above, but GRACE risk score >140
Temporal change in Tn (Section 3.4)
New or presumably new ST depression
Delayed invasive (within 25−72 h)None of the above but diabetes mellitus
Renal insufficiency (GFR <60 mL/min/1.73 m2)
Reduced LV systolic function (EF <0.40)
Early postinfarction angina
PCI within 6 mo
Prior CABG
GRACE risk score 109–140; TIMI score ≥2

CABG indicates coronary artery bypass graft; EF, ejection fraction; GFR, glomerular filtration rate; GRACE, Global Registry of Acute Coronary Events; HF, heart failure; LV, left ventricular; NSTE-ACS, non–ST-elevation acute coronary syndrome; PCI, percutaneous coronary intervention; TIMI, Thrombolysis In Myocardial Infarction; Tn, troponin; VF, ventricular fibrillation; and VT, ventricular tachycardia.

4.5 Risk Stratification Before Discharge for Patients With an Ischemia-Guided Strategy of NSTE-ACS

Class I

1.

Noninvasive stress testing is recommended in low- and intermediate-risk patients who have been free of ischemia at rest or with low-level activity for a minimum of 12 to 24 hours (179–183). (Level of Evidence: B)

2.

Treadmill exercise testing is useful in patients able to exercise in whom the ECG is free of resting ST changes that may interfere with interpretation (179–182). (Level of Evidence: C)

3.

Stress testing with an imaging modality should be used in patients who are able to exercise but have ST changes on resting ECG that may interfere with interpretation. In patients undergoing a low-level exercise test, an imaging modality can add prognostic information (179–182). (Level of Evidence: B)

4.

Pharmacological stress testing with imaging is recommended when physical limitations preclude adequate exercise stress. (Level of Evidence: C)

5.

A noninvasive imaging test is recommended to evaluate LV function in patients with definite ACS (179–182). (Level of Evidence: C)

5 Myocardial Revascularization: Recommendations

5.1 PCI—General Considerations

Class IIb

1.

A strategy of multivessel PCI, in contrast to culprit lesion−only PCI, may be reasonable in patients undergoing coronary revascularization as part of treatment for NSTE-ACS (169,184–189). (Level of Evidence: B)

5.1.1 PCI—Oral and Intravenous Antiplatelet Agents

Class I

1.

Patients already taking daily aspirin before PCI should take 81 mg to 325 mg non–enteric-coated aspirin before PCI (27,190–192). (Level of Evidence: B)

2.

Patients not on aspirin therapy should be given non−enteric-coated aspirin 325 mg as soon as possible before PCI (27,190–192). (Level of Evidence: B)

3.

After PCI, aspirin should be continued indefinitely at a dose of 81 mg to 325 mg daily (28,142,193). (Level of Evidence: B)

4.

A loading dose of a P2Y12 receptor inhibitor should be given before the procedure in patients undergoing PCI with stenting (27,147,170,172,194–197). (Level of Evidence: A) Options include:

a.

Clopidogrel: 600 mg (170,194–196,198–200)(Level of Evidence: B) or

b.

Prasugrel#

Patients should receive a loading dose of prasugrel provided that they were not pretreated with another P2Y12 receptor inhibitor.

: 60 mg (172)(Level of Evidence: B) or

c.

Ticagrelor

The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily (144).

: 180 mg (147)(Level of Evidence: B)

5.

In patients with NSTE-ACS and high-risk features (e.g., elevated troponin) who are not adequately pretreated with clopidogrel or ticagrelor, it is useful to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-dose bolus tirofiban) at the time of PCI (201–204). (Level of Evidence: A)

6.

In patients receiving a stent (bare-metal stent or drug-eluting stent [DES]) during PCI for NSTE-ACS, P2Y12 inhibitor therapy should be given for at least 12 months (169). Options include:

a.

Clopidogrel: 75 mg daily (170,171)(Level of Evidence: B) or

b.

Prasugrel#

Patients should receive a loading dose of prasugrel provided that they were not pretreated with another P2Y12 receptor inhibitor.

: 10 mg daily (172)(Level of Evidence: B) or

c.

Ticagrelor

The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily (144).

: 90 mg twice daily (147)(Level of Evidence: B)

Class IIa

1.

It is reasonable to choose ticagrelor over clopidogrel for P2Y12 inhibition treatment in patients with NSTE-ACS treated with an early invasive strategy and/or coronary stenting (147,148). (Level of Evidence: B)

2.

It is reasonable to choose prasugrel over clopidogrel for P2Y12 treatment in patients with NSTE-ACS who undergo PCI who are not at high risk of bleeding complications (172,205). (Level of Evidence: B)

3.

In patients with NSTE-ACS and high-risk features (e.g., elevated troponin) treated with UFH and adequately pretreated with clopidogrel, it is reasonable to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-bolus dose tirofiban) at the time of PCI (206–208). (Level of Evidence: B)

4.

After PCI, it is reasonable to use 81 mg per day of aspirin in preference to higher maintenance doses (170,190,209–212). (Level of Evidence: B)

5.

If the risk of morbidity from bleeding outweighs the anticipated benefit of a recommended duration of P2Y12 inhibitor therapy after stent implantation, earlier discontinuation (e.g., <12 months) of P2Y12 inhibitor therapy is reasonable (169). (Level of Evidence: C)

Class IIb

1.

Continuation of DAPT beyond 12 months may be considered in patients undergoing stent implantation. (Level of Evidence: C)

Class III: Harm

1.

Prasugrel should not be administered to patients with a prior history of stroke or transient ischemic attack (172). (Level of Evidence: B)

5.1.1.1 PCI—GP IIb/IIIa Inhibitors

Class I

1.

In patients with NSTE-ACS and high-risk features (e.g., elevated troponin) and not adequately pretreated with clopidogrel or ticagrelor, it is useful to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-dose bolus tirofiban) at the time of PCI (201–204). (Level of Evidence: A)

Class IIa

1.

In patients with NSTE-ACS and high-risk features (e.g., elevated troponin) treated with UFH and adequately pretreated with clopidogrel, it is reasonable to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-dose bolus tirofiban) at the time of PCI (206,207). (Level of Evidence: B)

5.1.2 Anticoagulant Therapy in Patients Undergoing PCI

See Table 9 for dosing information on dosing of parenteral anticoagulants during PCI.

Class I

1.

An anticoagulant should be administered to patients with NSTE-ACS undergoing PCI to reduce the risk of intracoronary and catheter thrombus formation. (Level of Evidence: C)

2.

Intravenous UFH is useful in patients with NSTE-ACS undergoing PCI. (Level of Evidence: C)

3.

Bivalirudin is useful as an anticoagulant with or without prior treatment with UFH in patients with NSTE-ACS undergoing PCI (154,213–217). (Level of Evidence: B)

4.

An additional dose of 0.3 mg/kg IV enoxaparin should be administered at the time of PCI to patients with NSTE-ACS who have received fewer than 2 therapeutic subcutaneous doses (e.g., 1 mg/kg SC) or received the last subcutaneous enoxaparin dose 8 to 12 hours before PCI (152,218–222). (Level of Evidence: B)

5.

If PCI is performed while the patient is on fondaparinux, an additional 85 IU/kg of UFH should be given intravenously immediately before PCI because of the risk of catheter thrombosis (60 IU/kg IV if a GP IIb/IIIa inhibitor used with UFH dosing based on the target-activated clotting time) (27,157–159,223). (Level of Evidence: B)

6.

In patients with NSTE-ACS, anticoagulant therapy should be discontinued after PCI unless there is a compelling reason to continue such therapy. (Level of Evidence: C)

Class IIa

1.

In patients with NSTE-ACS undergoing PCI who are at high risk of bleeding, it is reasonable to use bivalirudin monotherapy in preference to the combination of UFH and a GP IIb/IIIa receptor antagonist (154,215). (Level of Evidence: B)

Class IIb

1.

Performance of PCI with enoxaparin may be reasonable in patients treated with upstream subcutaneous enoxaparin for NSTE-ACS (27,152,218–221,224,225). (Level of Evidence: B)

Class III: Harm

1.

Fondaparinux should not be used as the sole anticoagulant to support PCI in patients with NSTE-ACS due to an increased risk of catheter thrombosis (27,157–159). (Level of Evidence: B)

Table 9. Dosing of Parenteral Anticoagulants During PCI

DrugIn Patients Who Have Received
Prior Anticoagulant Therapy
In Patients Who Have Not Received
Prior Anticoagulant Therapy
Enoxaparin

For prior treatment with enoxaparin, if last SC dose was administered 8−12 h earlier or if <2 therapeutic SC doses of enoxaparin have been administered, an IV dose of enoxaparin 0.3 mg/kg should be given

If the last SC dose was administered within prior 8 h, no additional enoxaparin should be given

0.5 mg/kg–0.75 mg/kg IV loading dose

Bivalirudin

For patients who have received UFH, wait 30 min, then give 0.75 mg/kg IV loading dose, then 1.75 mg/kg/h IV infusion

For patients already receiving bivalirudin infusion, give additional loading dose 0.5 mg/kg and increase infusion to 1.75 mg/kg/h during PCI

0.75 mg/kg loading dose, 1.75 mg/kg/h IV infusion

Fondaparinux

For prior treatment with fondaparinux, administer additional IV treatment with anticoagulant possessing anti-IIa activity, considering whether GPI receptor antagonists have been administered

N/A
UFH

IV GPI planned: additional UFH as needed (e.g., 2,000–5,000 U) to achieve ACT of 200–250 s

No IV GPI planned: additional UFH as needed (e.g., 2,000–5,000 U) to achieve ACT of 250–300 s for HemoTec, 300–350 s for Hemochron

IV GPI planned: 50–70 U/kg loading dose to achieve ACT of 200–250 s

No IV GPI planned: 70–100 U/kg loading dose to achieve target ACT of 250–300 s for HemoTec, 300–350 s for Hemochron

ACT indicates activated clotting time; COR, Class of Recommendation; GPI, glycoprotein IIb/IIIa inhibitor; IV, intravenous; LOE, Level of Evidence; N/A, not applicable; PCI, percutaneous coronary intervention; SC, subcutaneous; and UFH, unfractionated heparin.

∗ Drugs presented in order of the COR and then the LOE as noted in the Preamble. When more than 1 drug exists within the same LOE, and there are no comparative data, then the drugs are listed alphabetically.

5.2 Timing of Urgent Coronary Artery Bypass Graft in Patients With NSTE-ACS in Relation to Use of Antiplatelet Agents

Class I

1.

Non–enteric-coated aspirin (81 mg to 325 mg daily) should be administered preoperatively to patients undergoing coronary artery bypass graft (CABG) (226–228). (Level of Evidence: B)

2.

In patients referred for elective CABG, clopidogrel and ticagrelor should be discontinued for at least 5 days before surgery (24,229–231)(Level of Evidence: B) and prasugrel for at least 7 days before surgery (9,232). (Level of Evidence: C)

3.

In patients referred for urgent CABG, clopidogrel and ticagrelor should be discontinued for at least 24 hours to reduce major bleeding (9,230,233–235). (Level of Evidence: B)

4.

In patients referred for CABG, short-acting intravenous GP IIb/IIIa inhibitors (eptifibatide or tirofiban) should be discontinued for at least 2 to 4 hours before surgery (236,237) and abciximab for at least 12 hours before to limit blood loss and transfusion (238). (Level of Evidence: B)

Class IIb

1.

In patients referred for urgent CABG, it may be reasonable to perform surgery less than 5 days after clopidogrel or ticagrelor has been discontinued and less than 7 days after prasugrel has been discontinued. (Level of Evidence: C)

6 Late Hospital Care, Hospital Discharge, and Posthospital Discharge Care: Recommendations

6.1 Medical Regimen and Use of Medications at Discharge

Class I

1.

Medications required in the hospital to control ischemia should be continued after hospital discharge in patients with NSTE-ACS who do not undergo coronary revascularization, patients with incomplete or unsuccessful revascularization, and patients with recurrent symptoms after revascularization. Titration of the doses may be required (239,240). (Level of Evidence: C)

2.

All patients who are post−NSTE-ACS should be given sublingual or spray nitroglycerin with verbal and written instructions for its use (241). (Level of Evidence: C)

3.

Before hospital discharge, patients with NSTE-ACS should be informed about symptoms of worsening myocardial ischemia and MI and should be given verbal and written instructions about how and when to seek emergency care for such symptoms (241). (Level of Evidence: C)

4.

Before hospital discharge, patients who are post−NSTE-ACS and/or designated responsible caregivers should be provided with easily understood and culturally sensitive verbal and written instructions about medication type, purpose, dose, frequency, side effects, and duration of use (241). (Level of Evidence: C)

5.

For patients who are post−NSTE-ACS and have initial angina lasting more than 1 minute, nitroglycerin (1 dose sublingual or spray) is recommended if angina does not subside within 3 to 5 minutes; call 9-1-1 immediately to access emergency medical services (241). (Level of Evidence: C)

6.

If the pattern or severity of angina changes, suggesting worsening myocardial ischemia (e.g., pain is more frequent or severe or is precipitated by less effort or occurs at rest), patients should contact their clinician without delay to assess the need for additional treatment or testing (241). (Level of Evidence: C)

7.

Before discharge, patients should be educated about modification of cardiovascular risk factors (240). (Level of Evidence: C)

6.2 Late Hospital and Posthospital Oral Antiplatelet Therapy

Class I

1.

Aspirin should be continued indefinitely. The maintenance dose should be 81 mg daily in patients treated with ticagrelor and 81 mg to 325 mg daily in all other patients (142–144). (Level of Evidence: A)

2.

In addition to aspirin, a P2Y12 inhibitor (either clopidogrel or ticagrelor) should be continued for up to 12 months in all patients with NSTE-ACS without contraindications who are treated with an ischemia-guided strategy. Options include:

Clopidogrel: 75 mg daily (143,171)(Level of Evidence: B) or

Ticagrelor: 90 mg twice daily (147,148)(Level of Evidence: B)

3.

In patients receiving a stent (bare-metal stent or DES) during PCI for NSTE-ACS, P2Y12 inhibitor therapy should be given for at least 12 months (169). Options include:

Clopidogrel: 75 mg daily (170,171)(Level of Evidence: B) or

Prasugrel#

Patients should receive a loading dose of prasugrel provided that they were not pretreated with another P2Y12 receptor inhibitor.

: 10 mg daily (172)(Level of Evidence: B) or

Ticagrelor

The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily (144).

: 90 mg twice daily (147)(Level of Evidence: B)

Class IIa

1.

It is reasonable to use an aspirin maintenance dose of 81 mg per day in preference to higher maintenance doses in patients with NSTE-ACS treated either invasively or with coronary stent implantation (27,170,190,209–212). (Level of Evidence: B)

2.

It is reasonable to use ticagrelor in preference to clopidogrel for maintenance P2Y12 treatment in patients with NSTE-ACS who undergo an early invasive or ischemia-guided strategy (147,148). (Level of Evidence: B)

3.

It is reasonable to choose prasugrel over clopidogrel for maintenance P2Y12 treatment in patients with NSTE-ACS who undergo PCI who are not at high risk for bleeding complications (172,205). (Level of Evidence: B)

4.

If the risk of morbidity from bleeding outweighs the anticipated benefit of a recommended duration of P2Y12 inhibitor therapy after stent implantation, earlier discontinuation (e.g., <12 months) of P2Y12 inhibitor therapy is reasonable (169). (Level of Evidence: C)

Class IIb

1.

Continuation of DAPT beyond 12 months may be considered in patients undergoing stent implantation. (Level of Evidence: C)

6.3 Combined Oral Anticoagulant Therapy and Antiplatelet Therapy in Patients With NSTE-ACS

Class I

1.

The duration of triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor in patients with NSTE-ACS should be minimized to the extent possible to limit the risk of bleeding. (Level of Evidence: C)

2.

Proton pump inhibitors should be prescribed in patients with NSTE-ACS with a history of gastrointestinal bleeding who require triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor (27,242,243). (Level of Evidence: C)

Class IIa

1.

Proton pump inhibitor use is reasonable in patients with NSTE-ACS without a known history of gastrointestinal bleeding who require triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor (27,242,243). (Level of Evidence: C)

Class IIb

1.

Targeting oral anticoagulant therapy to a lower international normalized ratio (e.g., 2.0 to 2.5) may be reasonable in patients with NSTE-ACS managed with aspirin and a P2Y12 inhibitor. (Level of Evidence: C)

6.4 Risk Reduction Strategies for Secondary Prevention

Class I

1.

All eligible patients with NSTE-ACS should be referred to a comprehensive cardiovascular rehabilitation program either before hospital discharge or during the first outpatient visit (244–247). (Level of Evidence: B)

2.

The pneumococcal vaccine is recommended for patients 65 years of age and older and in high-risk patients with cardiovascular disease (248–250). (Level of Evidence: B)

3.

Patients should be educated about appropriate cholesterol management, blood pressure (BP), smoking cessation, and lifestyle management (16,17,19). (Level of Evidence: C)

4.

Patients who have undergone PCI or CABG derive benefit from risk factor modification and should receive counseling that revascularization does not obviate the need for lifestyle changes (251). (Level of Evidence: C)

5.

Before hospital discharge, the patient’s need for treatment of chronic musculoskeletal discomfort should be assessed, and a stepped-care approach should be used for selection of treatments. Pain treatment before consideration of NSAIDs should begin with acetaminophen, nonacetylated salicylates, tramadol, or small doses of narcotics if these medications are not adequate (18,252). (Level of Evidence: C)

Class IIa

1.

It is reasonable to use nonselective NSAIDs, such as naproxen, if initial therapy with acetaminophen, nonacetylated salicylates, tramadol, or small doses of narcotics is insufficient (252). (Level of Evidence: C)

Class IIb

1.

NSAIDs with increasing degrees of relative cyclooxygenase-2 selectivity may be considered for pain relief only for situations in which intolerable discomfort persists despite attempts at stepped-care therapy with acetaminophen, nonacetylated salicylates, tramadol, small doses of narcotics, or nonselective NSAIDs. In all cases, use of the lowest effective doses for the shortest possible time is encouraged (117,118,252,253). (Level of Evidence: C)

Class III: No Benefit

1.

Antioxidant vitamin supplements (e.g., vitamins E, C, or beta carotene) should not be used for secondary prevention in patients with NSTE-ACS (254,255). (Level of Evidence: A)

2.

Folic acid, with or without vitamins B6 and B12, should not be used for secondary prevention in patients with NSTE-ACS (256,257). (Level of Evidence: A)

Class III: Harm

1.

Hormone therapy with estrogen plus progestin, or estrogen alone, should not be given as new drugs for secondary prevention of coronary events to postmenopausal women after NSTE-ACS and should not be continued in previous users unless the benefits outweigh the estimated risks (18,258–260). (Level of Evidence: A)

2.

NSAIDs with increasing degrees of relative cyclooxygenase-2 selectivity should not be administered to patients with NSTE-ACS and chronic musculoskeletal discomfort when therapy with acetaminophen, nonacetylated salicylates, tramadol, small doses of narcotics, or nonselective NSAIDs provide acceptable pain relief (117,118,252,253). (Level of Evidence: B)

6.5 Plan of Care for Patients With NSTE-ACS

Class I

1.

Posthospital systems of care designed to prevent hospital readmissions should be used to facilitate the transition to effective, coordinated outpatient care for all patients with NSTE-ACS (261–265). (Level of Evidence: B)

2.

An evidence-based plan of care (e.g., GDMT) that promotes medication adherence, timely follow-up with the healthcare team, appropriate dietary and physical activities, and compliance with interventions for secondary prevention should be provided to patients with NSTE-ACS. (Level of Evidence: C)

3.

In addition to detailed instructions for daily exercise, patients should be given specific instruction on activities (e.g., lifting, climbing stairs, yard work, and household activities) that are permissible and those to avoid. Specific mention should be made of resumption of driving, return to work, and sexual activity (247,266,267). (Level of Evidence: B)

4.

An annual influenza vaccination is recommended for patients with cardiovascular disease (28,268). (Level of Evidence: C)

7 Special Patient Groups: Recommendations

See Table 10 for summary of recommendations for this section.

Table 10. Summary of Recommendations for Special Patient Groups

RecommendationsCORLOEReferences
NSTE-ACS in older patients
Treat older patients (≥75 y of age) with GDMT, early invasive strategy, and revascularization as appropriateIA(269–273)
Individualize pharmacotherapy in older patients, with dose adjusted by weight and/or CrCl to reduce adverse events caused by age-related changes in pharmacokinetics/dynamics, volume of distribution, comorbidity, drug interactions, and increased drug sensitivityIA(269,274–276)
Undertake patient-centered management for older patients, considering patient preferences/goals, comorbidities, functional and cognitive status, and life expectancyIB(269,277–279)
Bivalirudin rather than GP IIb/IIIa inhibitor plus UFH is reasonable for older patients (≥75 y of age), given similar efficacy but less bleeding riskIIaB(215,280–282)
It is reasonable to choose CABG over PCI in older patients, particularly those with DM or multivessel disease, because of the potential for improved survival and reduced CVD eventsIIaB(283–288)
HF and cardiogenic shock
Treat patients with a history of HF according to the same risk stratification guidelines and recommendations for patients without HFIB(15,40–42,52–58)
Select a revascularization strategy based on the extent of CAD, associated cardiac lesions, LV dysfunction, and prior revascularizationIB(15,173,175,177,178,289–292)
Recommend early revascularization for cardiogenic shock due to cardiac pump failureIB(291,293,294)
DM
Recommend medical treatment and decisions for testing and revascularization similar to those for patients without DMIA(173,176,295)
Post–CABG
Recommend GDMT antiplatelet and anticoagulant therapy and early invasive strategy because of increased risk with prior CABGIB(44,45,178,290,296,297)
Perioperative NSTE-ACS
Administer GDMT to perioperative patients with limitations imposed by noncardiac surgeryIC(298,299)
Direct management at underlying cause of perioperative NSTE-ACSIC(22,298–306)
CKD
Estimate CrCl and adjust doses of renally cleared medications according to pharmacokinetic dataIB(307,308)
Administer adequate hydration to patients undergoing coronary and LV angiographyICN/A
Invasive strategy is reasonable in patients with mild (stage 2) and moderate (stage 3) CKDIIaB(307–310)
Women
Manage women with the same pharmacological therapy as that for men for acute care and secondary prevention, with attention to weight and/or renally calculated doses of antiplatelet and anticoagulant agents to reduce bleeding riskIB(311–315)
Early invasive strategy is recommended in women with NSTE-ACS and high-risk features (troponin positive)IA(178,292,316,317)
Myocardial revascularization is reasonable for pregnant women if ischemia-guided strategy is ineffective for management of life-threatening complicationsIIaC(318)
Women with low-risk features (Section 3.3.1 in the full-text CPG) should not undergo early invasive treatment because of lack of benefit and the possibility of harmIII: No BenefitB(178,316,317)
Anemia, bleeding, and transfusion
Evaluate all patients for risk of bleedingICN/A
Recommend that anticoagulant and antiplatelet therapy be weight-based where appropriate and adjusted for CKD to decrease the risk of bleedingIB(276,319,320)
There is no benefit of routine blood transfusion in hemodynamically stable patients with hemoglobin levels >8 g/dLIII: No BenefitB(321–325)
Cocaine and methamphetamine users
Manage patients with recent cocaine or methamphetamine use similarly to those without cocaine- or methamphetamine-related NSTE-ACS. The exception is in patients with signs of acute intoxication (e.g., euphoria, tachycardia, and hypertension) and beta-blocker use unless patients are receiving coronary vasodilator therapyICN/A
It is reasonable to use benzodiazepines alone or in combination with NTG to manage hypertension and tachycardia and signs of acute cocaine or methamphetamine intoxicationIIaC(326–329)
Do not administer beta blockers to patients with recent cocaine or methamphetamine use who have signs of acute intoxication due to risk of potentiating coronary spasmIII: HarmCN/A
Vasospastic (Prinzmetal) angina
Recommend CCBs alone or in combination with nitratesIB(330–335)
Recommend HMG-CoA reductase inhibitor, cessation of tobacco use, and atherosclerosis risk factor modificationIB(336–340)
Recommend coronary angiography (invasive or noninvasive) for episodic chest pain with transient ST-elevation to detect severe CADICN/A
Provocative testing during invasive coronary angiography may be considered for suspected vasospastic angina when clinical criteria and noninvasive assessment fail to determine diagnosisIIbB(341–344)
ACS with angiographically normal coronary arteries
Invasive physiological assessment (coronary flow reserve measurement) may be considered with normal coronary arteries if endothelial dysfunction is suspectedIIbB(301,345–348)
Stress (Takotsubo) cardiomyopathy
Consider stress-induced cardiomyopathy in patients with apparent ACS and nonobstructive CADICN/A
Perform ventriculography, echocardiography, or MRI to confirm or exclude diagnosisIB(349–352)
Treat with conventional agents (ACE inhibitors, beta blockers, aspirin, and diuretics) if hemodynamically stableICN/A
Administer anticoagulant therapy for LV thrombiICN/A
It is reasonable to administer catecholamines for symptomatic hypotension in the absence of LV outflow tract obstructionIIaCN/A
It is reasonable to use IABP for refractory shockIIaCN/A
It is reasonable to use beta blockers and alpha-adrenergic agents for LV outflow tract obstructionIIaCN/A
Prophylactic anticoagulation may be considered to prevent LV thrombiIIbCN/A

ACE indicates angiotensin-converting enzyme; ACS, acute coronary syndrome; CABG, coronary artery bypass graft; CAD, coronary artery disease; CCB, calcium channel blocker; CKD, chronic kidney disease; COR, Class of Recommendation; CPG, clinical practice guideline; CrCl, creatinine clearance; CVD, cardiovascular disease; DM, diabetes mellitus; GDMT, guideline-directed medical therapy; GP, glycoprotein; HF, heart failure; IABP, intra-aortic balloon pump; LOE, Level of Evidence; LV, left ventricular; MRI, magnetic resonance imaging; N/A, not available; NSTE-ACS, non–ST-elevation acute coronary syndrome; NTG, nitroglycerin; PCI, percutaneous coronary intervention; and UFH, unfractionated heparin.

∗ Provocative testing during invasive coronary angiography (e.g., using ergonovine, acetylcholine, methylergonovine) is relatively safe, especially when performed in a controlled manner by experienced operators. However, sustained spasm, serious arrhythmias, and even death can also occur but very infrequently. Therefore, provocative tests should be avoided in patients with significant left main disease, advanced 3-vessel disease, presence of high-grade obstructive lesions, significant valvular stenosis, significant LV systolic dysfunction, and advanced HF.

7.1 NSTE-ACS in Older Patients

Class I

1.

Older patients∗∗

Those ≥75 years of age (see Section 7.1 in the full-text CPG).

with NSTE-ACS should be treated with GDMT, an early invasive strategy, and revascularization as appropriate (269–273). (Level of Evidence: A)

2.

Pharmacotherapy in older patients∗∗ with NSTE-ACS should be individualized and dose adjusted by weight and/or CrCl to reduce adverse events caused by age-related changes in pharmacokinetics/dynamics, volume of distribution, comorbidities, drug interactions, and increased drug sensitivity (269,274–276). (Level of Evidence: A)

3.

Management decisions for older patients∗∗ with NSTE-ACS should be patient centered, considering patient preferences/goals, comorbidities, functional and cognitive status, and life expectancy (269,277–279). (Level of Evidence: B)

Class IIa

1.

Bivalirudin, rather than a GP IIb/IIIa inhibitor plus UFH, is reasonable in older patients∗∗ with NSTE-ACS, both initially and at PCI, given similar efficacy but less bleeding risk (215,280–282). (Level of Evidence: B)

2.

It is reasonable to choose CABG over PCI in older patients∗∗ with NSTE-ACS who are appropriate candidates, particularly those with diabetes mellitus or complex 3-vessel CAD (e.g., SYNTAX score >22), with or without involvement of the proximal left anterior descending artery, to reduce cardiovascular disease events and readmission and to improve survival (283–288). (Level of Evidence: B)

7.2 Heart Failure and Cardiogenic Shock

Class I

1.

Patients with a history of HF and NSTE-ACS should be treated according to the same risk stratification guidelines and recommendations for patients without HF (15,40–42,52–58). (Level of Evidence: B)

2.

Selection of a specific revascularization strategy should be based on the degree, severity, and extent of CAD; associated cardiac lesions; the extent of LV dysfunction; and the history of prior revascularization procedures (15,173,175,177,178,289–292). (Level of Evidence: B)

3.

Early revascularization is recommended in suitable patients with cardiogenic shock due to cardiac pump failure after NSTE-ACS (291,293,294). (Level of Evidence: B)

7.3 Diabetes Mellitus

Class I

1.

Medical treatment in the acute phase of NSTE-ACS and decisions to perform stress testing, angiography, and revascularization should be similar in patients with and without diabetes mellitus (173,176,295). (Level of Evidence: A)

7.4 Post–CABG

Class I

1.

Patients with prior CABG and NSTE-ACS should receive antiplatelet and anticoagulant therapy according to GDMT and should be strongly considered for early invasive strategy because of their increased risk (44,45,178,290,296,297). (Level of Evidence: B)

7.5 Perioperative NSTE-ACS Related to Noncardiac Surgery

Class I

1.

Patients who develop NSTE-ACS following noncardiac surgery should receive GDMT as recommended for patients in the general population but with the modifications imposed by the specific noncardiac surgical procedure and the severity of NSTE-ACS (298,299). (Level of Evidence: C)

2.

In patients who develop NSTE-ACS after noncardiac surgery, management should be directed at the underlying cause (22,298–306). (Level of Evidence: C)

7.6 Chronic Kidney Disease

Class I

1.

CrCl should be estimated in patients with NSTE-ACS, and doses of renally cleared medications should be adjusted according to the pharmacokinetic data for specific medications (307,308). (Level of Evidence: B)

2.

Patients undergoing coronary and LV angiography should receive adequate hydration. (Level of Evidence: C)

Class IIa

1.

An invasive strategy is reasonable in patients with mild (stage 2) and moderate (stage 3) CKD (307–310). (Level of Evidence: B)

7.7 Women

Class I

1.

Women with NSTE-ACS should be managed with the same pharmacological therapy as that for men for acute care and for secondary prevention, with attention to weight and/or renally-calculated doses of antiplatelet and anticoagulant agents to reduce bleeding risk (311–315). (Level of Evidence: B)

2.

Women with NSTE-ACS and high-risk features (e.g., troponin positive) should undergo an early invasive strategy (178,292,316,317). (Level of Evidence: A)

Class IIa

1.

Myocardial revascularization is reasonable in pregnant women with NSTE-ACS if an ischemia-guided strategy is ineffective for management of life-threatening complications (318). (Level of Evidence: C)

Class III: No Benefit

1.

Women with NSTE-ACS and low-risk features (see Section 3.3.1 in the full-text CPG) should not undergo early invasive treatment because of the lack of benefit (178,316,317) and the possibility of harm (178). (Level of Evidence: B)

7.8 Anemia, Bleeding, and Transfusion

Class I

1.

All patients with NSTE-ACS should be evaluated for the risk of bleeding. (Level of Evidence: C)

2.

Anticoagulant and antiplatelet therapy should be weight-based where appropriate and should be adjusted when necessary for CKD to decrease the risk of bleeding in patients with NSTE-ACS (276,319,320). (Level of Evidence: B)

Class III: No Benefit

1.

A strategy of routine blood transfusion in hemodynamically stable patients with NSTE-ACS and hemoglobin levels greater than 8 g/dL is not recommended (321–325). (Level of Evidence: B)

7.9 Cocaine and Methamphetamine Users

Class I

1.

Patients with NSTE-ACS and a recent history of cocaine or methamphetamine use should be treated in the same manner as patients without cocaine- or methamphetamine-related NSTE-ACS. The only exception is in patients with signs of acute intoxication (e.g., euphoria, tachycardia, and/or hypertension) and beta-blocker use, unless patients are receiving coronary vasodilator therapy. (Level of Evidence: C)

Class IIa

1.

Benzodiazepines alone or in combination with nitroglycerin are reasonable for management of hypertension and tachycardia in patients with NSTE-ACS and signs of acute cocaine or methamphetamine intoxication (326–329). (Level of Evidence: C)

Class III: Harm

1.

Beta blockers should not be administered to patients with ACS with a recent history of cocaine or methamphetamine use who demonstrate signs of acute intoxication due to the risk of potentiating coronary spasm. (Level of Evidence: C)

7.10 Vasospastic (Prinzmetal) Angina

Class I

1.

CCBs alone (330–334) or in combination with long-acting nitrates (332,335) are useful to treat and reduce the frequency of vasospastic angina. (Level of Evidence: B)

2.

Treatment with HMG-CoA reductase inhibitor (336,337), cessation of tobacco use (338,339), and additional atherosclerosis risk factor modification (339,340) are useful in patients with vasospastic angina. (Level of Evidence: B)

3.

Coronary angiography (invasive or noninvasive) is recommended in patients with episodic chest pain accompanied by transient ST-elevation to rule out severe obstructive CAD. (Level of Evidence: C)

Class IIb

1.

Provocative testing during invasive coronary angiography††

Provocative testing during invasive coronary angiography (e.g., using ergonovine, acetylcholine, methylergonovine) is relatively safe, especially when performed in a controlled manner by experienced operators. However, sustained spasm, serious arrhythmias, and even death can also occur very infrequently. Therefore, provocative testing should be avoided in patients with significant left main disease, advanced 3-vessel disease, presence of high-grade obstructive lesions, significant valvular stenosis, significant LV systolic dysfunction, and advanced HF.

may be considered in patients with suspected vasospastic angina when clinical criteria and noninvasive testing fail to establish the diagnosis (341–344). (Level of Evidence: B)

7.11 ACS With Angiographically Normal Coronary Arteries

Class IIb

1.

If coronary angiography reveals normal coronary arteries and endothelial dysfunction is suspected, invasive physiological assessment such as coronary flow reserve measurement may be considered (301,345–348). (Level of Evidence: B)

7.12 Stress (Takotsubo) Cardiomyopathy

Class I

1.

Stress (Takotsubo) cardiomyopathy should be considered in patients who present with apparent ACS and nonobstructive CAD at angiography. (Level of Evidence: C)

2.

Imaging with ventriculography, echocardiography, or magnetic resonance imaging should be performed to confirm or exclude the diagnosis of stress (Takotsubo) cardiomyopathy (349–352). (Level of Evidence: B)

3.

Patients should be treated with conventional agents (ACE inhibitors, beta blockers, aspirin, and diuretics) as otherwise indicated if hemodynamically stable. (Level of Evidence: C)

4.

Anticoagulation should be administered in patients who develop LV thrombi. (Level of Evidence: C)

Class IIa

1.

It is reasonable to use catecholamines for patients with symptomatic hypotension if outflow tract obstruction is not present. (Level of Evidence: C)

2.

The use of an intra-aortic balloon pump is reasonable for patients with refractory shock. (Level of Evidence: C)

3.

It is reasonable to use beta blockers and alpha-adrenergic agents in patients with outflow tract obstruction. (Level of Evidence: C)

Class IIb

1.

Prophylactic anticoagulation may be considered to inhibit the development of LV thrombi. (Level of Evidence: C)

8 Quality of Care and Outcomes for ACS—Use of Performance Measures and Registries: Recommendation

Class IIa

1.

Participation in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and performance measures can be beneficial in improving the quality of NSTE-ACS care (353–361). (Level of Evidence: B)

9 Summary and Evidence Gaps

Despite landmark advances in the care of patients with NSTE-ACS since the publication of the 2007 UA/NSTEMI CPG (362), many emerging diagnostic and therapeutic strategies have posed new challenges. There is general acceptance of an early invasive strategy for patients with NSTE-ACS in whom significant coronary vascular obstruction has been precisely quantified. Low-risk patients with NSTE-ACS are documented to benefit substantially from GDMT, but this is often suboptimally used. Advances in noninvasive testing have the potential to identify patients with NSTE-ACS who are at intermediate risk and are candidates for invasive versus medical therapy.

Newer, more potent antiplatelet agents in addition to anticoagulant therapy are indicated irrespective of initial treatment strategy. Evidence-based decisions will require comparative-effectiveness studies of available and novel agents. The paradox of newer and more potent antithrombotic and anticoagulant drugs that reduce major adverse cardiac outcomes but increase bleeding risk occurs with greater frequency in patients with atrial fibrillation. Patients with atrial fibrillation who develop NSTE-ACS and receive a coronary stent are the population at risk from triple anticoagulant/antiplatelet therapy. This regimen has been reported to be safely modified by elimination of aspirin, a finding that requires confirmation.

Among the most rapidly evolving areas in NSTE-ACS diagnosis is the use of cardiac troponin, the preferred biomarker of myocardial necrosis. Although a truly high-sensitivity cardiac troponin is not available in the United States at the time this CPG was prepared, the sensitivity of contemporary assays continues to increase. This change is accompanied by higher rates of elevated cardiac troponin unrelated to coronary plaque rupture. The diagnostic quandary posed by these findings necessitates investigation to elucidate the optimal utility of this advanced biomarker. A promising approach to improve the diagnostic accuracy for detecting myocardial necrosis is measurement of absolute cardiac troponin change, which may be more accurate than the traditional analysis of relative alterations.

Special populations are addressed in this CPG, the most numerous of which are older persons and women. More than half of the mortality in NSTE-ACS occurs in older patients, and this high-risk cohort will increase as our population ages. An unmet need is to more clearly distinguish which older patients are candidates for an ischemia-guided strategy compared with an early invasive management strategy. An appreciable number of patients with NSTE-ACS have angiographically normal or nonobstructive CAD, a group in which women predominate. Their prognosis is not benign and the multiple mechanisms of ACS postulated for these patients remain largely speculative. Clinical advances are predicated on clarification of the pathophysiology of this challenging syndrome.

A fundamental aspect of all CPGs is that these carefully developed, evidence-based documents cannot encompass all clinical circumstances, nor can they replace the judgment of individual physicians in management of each patient. The science of medicine is rooted in evidence, and the art of medicine is based on the application of this evidence to the individual patient. This CPG has adhered to these principles for optimal management of patients with NSTE-ACS.

Presidents and Staff

American College of Cardiology

Patrick O’Gara, MD, FACC, President

Shalom Jacobovitz, Chief Executive Officer

William J. Oetgen, MD, MBA, FACC, Executive Vice President, Science, Education, and Quality

Amelia Scholtz, PhD, Publications Manager, Clinical Policy and Pathways

American College of Cardiology/American Heart Association

Lisa Bradfield, CAE, Director, Science and Clinical Policy

Emily Cottrell, MA, Quality Assurance Specialist, Science and Clinical Policy

Alexa Papaila, Specialist, Science and Clinical Policy

American Heart Association

Elliott Antman, MD, FAHA, President

Nancy Brown, Chief Executive Officer

Rose Marie Robertson, MD, FAHA, Chief Science Officer

Gayle R. Whitman, PhD, RN, FAHA, FAAN, Senior Vice President, Office of Science Operations

Marco Di Buono, PhD, Vice President, Science, Research, and Professional Education, Office of Science Operations

Jody Hundley, Production Manager, Scientific Publications, Office of Science Operations

Appendix 1

Author Relationships With Industry and Other Entities (Relevant)—2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes

Committee MemberEmploymentConsultantSpeakers BureauOwnership/Partnership/PrincipalPersonal ResearchInstitutional, Organizational, or Other Financial BenefitExpert WitnessVoting Recusals by Section
Ezra A. Amsterdam (Chair)University of California (Davis) Medical Center, Division of Cardiology—ProfessorNoneNoneNoneNoneNoneNoneNone
Nanette K. Wenger (Vice Chair)Emory University, School of Medicine—Professor of Medicine (Cardiology)

Abbott

Amgen

AstraZeneca

Gilead Sciences

Janssen Pharmaceuticals

Medtronic

Merck

Pfizer

NoneNone

Abbott

Eli Lilly

Gilead Sciences

Merck

Pfizer

NoneNoneAll sections except 3.1.1, 3.4, 5.2, 6.3.1, 6.3.2, 6.3.6, 7.5, 7.6, 7.8, and 8.
Ralph G. BrindisUniversity of California, San Francisco Department of Medicine and the Phillip R. Lee Institute for Health Policy Studies—Clinical Professor of MedicineNone

Volcano

NoneNoneNoneNoneNone
Donald E. Casey, JrAtlantic Health—Vice President of Health and Chief Medical OfficerNoneNoneNoneNoneNoneNoneNone
Theodore G. GaniatsUniversity of California, San Diego School of Medicine—Executive Director of Health Services Research CenterNoneNoneNoneNoneNoneNoneNone
David R. Holmes, JrMayo Clinic—Consultant, Cardiovascular DiseasesNoneNoneNoneNoneNoneNoneNone
Allan S. JaffeMayo Clinic, Cardiovascular Division—Professor of Medicine

Abbott

Alere

Amgen

Beckman-Coulter

Critical Diagnostics

ET Healthcare

Ortho Clinical Diagnostic

Radiometer

Roche

Thermo-Fisher

Trinity

NoneNoneNoneNoneNoneAll sections except 3.1, 3.1.1, 3.3, 4.1.2.1-4.1.2.3, 4.2, 4.3.1, 4.3.2, 4.5, 5.1, 5.2, 6.2.1, 6.3.1, 6.3.3, 6.3.6, 7.2.2, 7.5, 7.6, and 8.
Hani JneidBaylor College of Medicine—The Michael E. DeBakey VA Medical Center—Assistant Professor of MedicineNoneNoneNoneNoneNoneNoneNone
Rosemary F. KellyUniversity of Minnesota—Professor of Surgery; VA Medical Center—Chief, Cardiothoracic SurgeryNoneNoneNoneNoneNoneNoneNone
Michael C. KontosVirginia Commonwealth University, Pauley Heart Center—Medical Director, Coronary Intensive Care Unit, and Associate Professor, Internal Medicine

Astellas

General Electric

Ikaria

Prevencio

Sanofi-aventis

Wellpoint/Anthem

Astellas

AstraZeneca

NoneNone

Astellas

Eli Lilly

Merck

Novartis

NoneAll sections
Glenn N. LevineBaylor College of Medicine—Professor of Medicine; Director, Cardiac Care UnitNoneNoneNoneNoneNoneNoneNone
Philip R. LiebsonRush University Medical Center—McMullan-Eybel Chair of Excellence in Clinical Cardiology and Professor of Medicine and Preventive MedicineNoneNoneNoneNoneNoneNoneNone
Debabrata MukherjeeTexas Tech University Health Sciences Center—Chief, Cardiovascular MedicineNoneNoneNoneNoneNoneNoneNone
Eric D. PetersonDuke University Medical Center—Fred Cobb, MD, Distinguished Professor of Medicine; Duke Clinical Research Institute—Director

Boehringer Ingelheim

Genentech

Janssen Pharmaceuticals

Johnson & Johnson

Merck

NoneNone

Eli Lilly

Johnson & Johnson

Janssen Pharmaceuticals

DCRI has numerous grants and contracts sponsored by industry that are relevant to the content of this CPG. Dr. Peterson participated in discussions but recused himself from writing or voting, in accordance with ACC/AHA policy. See comprehensive RWI table for a complete list of companies pertaining to this organization.NoneAll sections
Marc S. SabatineBrigham and Women's Hospital, Chairman—TIMI Study Group, Division of Cardiovascular Medicine; Harvard Medical School—Professor of Medicine

Amgen

AstraZeneca

Bristol-Myers Squibb

Merck

Pfizer

Sanofi-aventis

NoneNone

Abbott Laboratories

Amgen

AstraZeneca

Bristol-Myers Squibb

BRAHMS

Critical Diagnostics

Daiichi-Sankyo

Genzyme

GlaxoSmithKline

Nanosphere

Roche Diagnostics

Sanofi-aventis

Takeda

AstraZeneca

Daiichi-Sankyo

Gilead

Johnson & Johnson

Merck

Proventys

Siemens

Singulex

NoneAll sections except 3.1.1, 5.2, 6.3.1, 6.3.2, 7.5, 7.8, and 8.
Richard W. SmallingUniversity of Texas, Health Science Center at Houston—Professor and Director of Interventional Cardiovascular Medicine; James D. Woods Distinguished Chair in Cardiovascular Medicine

Gilead

Maquet

NoneNone

Cordis

E-valve Abbott Vascular

Edwards Lifesciences

Gilead

Maquet Datascope

Cordis

E-valve

NoneAll sections except 3.1, 3.1.1, 3.3, 3.4, 3.5.1, 4.1.2.1-4.1.2.3, 4.2, 4.3.1, 4.3.2, 5.2, 6.2.1, 6.3.1, 6.3.2, 6.3.3, 6.3.6, 7.2.2, 7.5, 7.8, and 8.
Susan J. ZiemanNational Institute on Aging/NIH, Geriatrics Branch, Division of Geriatrics and Clinical Gerontology—Medical OfficerNoneNoneNoneNoneNoneNoneNone

This table represents the relationships of committee members with industry and other entities that were determined to be relevant to this document. These relationships were reviewed and updated in conjunction with all meetings and/or conference calls of the GWC during the document development process. The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of ≥5% of the voting stock or share of the business entity, or ownership of ≥$10,000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person’s gross income for the previous year. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted.

According to the ACC/AHA, a person has a relevant relationship IF: a) the relationship or interest relates to the same or similar subject matter, intellectual property or asset, topic, or issue addressed in the document; or b) the company/entity (with whom the relationship exists) makes a drug, drug class, or device addressed in the document, or makes a competing drug or device addressed in the document; or c) the person or a member of the person’s household, has a reasonable potential for financial, professional or other personal gain or loss as a result of the issues/content addressed in the document.

ACC indicates American College of Cardiology, AHA, American Heart Association, BMS, Bristol-Myers Squibb; CPG, clinical practice guideline; DCRI, Duke Clinical Research Institute; NIH, National Institutes of Health; NYU, New York University; RWI, relationships with industry and other entities; TIMI, Thrombolysis In Myocardial Infarction; and VA, Veterans Affairs.

∗ Writing members are required to recuse themselves from voting on sections to which their specific relationships with industry and other entities may apply. Section numbers pertain to those in the full-text CPG.

† Significant relationship.

‡ No financial benefit.

Appendix 2

Reviewer Relationships With Industry and Other Entities (Relevant)—2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes

ReviewerRepresentationEmploymentConsultantSpeakers BureauOwnership/Partnership/PrincipalPersonal ResearchInstitutional, Organizational, or Other Financial BenefitExpert Witness
Deepak L. BhattOfficial Reviewer—AHAVA Boston Healthcare System—Professor of Medicine, Harvard Medical School; Chief of Cardiology

BMS/Pfizer

DCRI (BMS/Pfizer)

DCRI (Eli Lilly)

Eli Lilly

NoneNone

AstraZeneca

Bristol-Myers Squibb

Ethicon

The Medicines Company

Medtronic

Sanofi-aventis

Takeda

Medscape Cardiology (Advisory Board)

WebMD (Steering Committee)

None
John E. Brush, JrOfficial Reviewer—ACC Board of TrusteesEastern Virginia Medical School—Professor of Medicine, Chief of CardiologyNoneNoneNoneNoneNoneNone
E. Magnus OhmanOfficial Reviewer—ACC/AHA Task Force on Practice GuidelinesDuke Medicine—Professor of Medicine

AstraZeneca

Bristol-Myers Squibb

Gilead

Janssen Pharmaceuticals

The Medicines Company

Merck

Pozen

Roche

Sanofi-aventis

Gilead

Janssen Pharmaceuticals

None

Daiichi-Sankyo

Eli Lilly

Gilead

NoneNone
John F. RobbOfficial Reviewer—ACC Board of GovernorsDartmouth-Hitchcock Medical Center—Director, Interventional Cardiology and Cardiac Catheterization LaboratoriesNoneNoneNoneNoneNone

Defendant, adverse drug reaction, 2012

Sarah A. SpinlerOfficial Reviewer—AHAPhiladelphia College of Pharmacy, University of the Sciences in Philadelphia—Professor of Clinical Pharmacy

Bristol-Myers Squibb

Daiichi-Sankyo

Janssen Pharmaceuticals

Merck

NoneNoneNoneNone

Plaintiff, clopidogrel, 2013

Gorav AilawadiOrganizational Reviewer—STSUniversity of Virginia Health System—Thoracic and Cardiovascular Surgery

Abbott

Atricure

NoneNoneNoneNoneNone
Srihari S. NaiduOrganizational Reviewer—SCAIWinthrop University Hospital—Director, Cardiac Catheterization LaboratoryNoneNoneNoneNoneNoneNone
Robert L. Rich, JrOrganizational Reviewer—AAFPBladen Medical Associates—Family PhysicianNoneNoneNoneNoneNoneNone
Mouaz H. Al-MallahContent Reviewer—ACC Prevention of Cardiovascular Disease CommitteeKing Abdul-Aziz Cardiac Center—Associate Professor of MedicineNoneNoneNoneNoneNoneNone
John A. AmbroseContent ReviewerUniversity of California San Francisco Fresno Department of Medicine—Professor of Medicine; Chief of Cardiology; Program Director, Cardiology FellowshipNoneNoneNoneNoneNoneNone
Giuseppe AmbrosioContent Reviewer—ACC Prevention of Cardiovascular Disease CommitteeHospital of University of Perugia School of Medicine—Medical Director, Division of Cardiology

Bayer

The Medicines Company

Merck Schering-Plough

Sanofi-aventis

Merck Schering-Plough

Pfizer

NoneNoneNoneNone
H. Vernon AndersonContent ReviewerUniversity of Texas—Professor of Medicine, Cardiology DivisionNoneNoneNoneNone

Eli Lilly

None
Jeffrey L. AndersonContent Reviewer—ACC/AHA Task Force on Practice GuidelinesIntermountain Medical Center—Associate Chief of Cardiology

Sanofi-aventis

NoneNone

GlaxoSmithKline

Harvard (DSMB)–TIMI -48, -51, and -54 Studies

NoneNone
Fred S. AppleContent ReviewerUniversity of Minnesota School of Medicine, Hennepin County Medical Center—Professor, Laboratory Medicine and Pathology

Abbott Diagnostics

Alere

Beckman Coulter

T2 Biosystems

NoneNone

Abbott

Alere/Biosite

Biomerieux

Ortho-Clinical Diagnostics

Radiometer

Roche Laboratories

Siemens

Abbott Diagnostics–PI

Alere–PI

Ortho-Clinical Diagnostics–PI

None
Emmanouil S. BrilakisContent Reviewer—ACC Interventional Section Leadership CouncilUT Southwestern Medical School—Director, Cardiac Catheterization Laboratory, VA North Texas Healthcare System

Bridgepoint Medical/Boston Scientific

Janssen Pharmaceuticals

Sanofi-aventis

NoneNoneNone

Abbott Vascular

AstraZeneca

Cordis

Daiichi-Sankyo

The Medicines Company

Medtronic

None
Matthew J. BudoffContent Reviewer—ACC Cardiovascular Imaging Section Leadership CouncilLos Angeles Biomedical Research Institute—Program Director, Division of Cardiology and Professor of MedicineNone

AstraZeneca

None

General Electric

None

Plaintiff, cardiac treatment, 2013

James A. BurkeContent Reviewer—ACC Interventional Section Leadership CouncilLehigh Valley Health Network—Interventional CardiologistNoneNoneNoneNoneNoneNone
Robert H. ChristensonContent Reviewer—AACCUniversity of Maryland School of Medicine—Professor of Pathology; Professor of Medical and Research Technology; Director, Rapid Response Laboratory

BG Medicine

Critical Diagnostics

Siemens Medical Diagnostics

NoneNone

The Medicines Company

AACC (President)

Roche Diagnostics (University of Maryland School of Medicine)

None
Joaquin E. CigarroaContent Reviewer—ACC Interventional Section Leadership CouncilOregon Health and Science University—Associate Professor of MedicineNoneNoneNoneNone

Catheterization and Cardiovascular Intervention (Editorial Board)

None
Marco A. CostaContent Reviewer—ACC Cardiovascular Imaging Section Leadership CouncilUniversity Hospital for Cleveland—Cardiologist

Abbott Vascular

Boston Scientific

Medtronic

NoneNone

Abbott Vascular

Boston Scientific

Cordis

IDEV Technology

The Medicines Company

Medtronic

Micell

OrbusNeich

Abbott

Cordis

Medtronic

None
Prakash C. DeedwaniaContent Reviewer—ACC Prevention of Cardiovascular Disease CommitteeUniversity of California San Francisco—Chief of Cardiology

Amgen

Pfizer

Pfizer

Takeda Pharmaceuticals

NoneNoneNoneNone
James A. de LemosContent ReviewerUT Southwestern Medical School—Associate Professor of Medicine; Director, Coronary Care Unit and Cardiology Fellowship

Diadexus

Janssen Pharmaceuticals

AstraZeneca

None

Abbott Diagnostics

Daiichi-Sankyo

None
Burl R. DonContent ReviewerUniversity of California Davis—Professor of Medicine; Director of Clinical NephrologyNoneNoneNoneNoneNoneNone
Lee A. FleisherContent ReviewerUniversity of Pennsylvania Department of Anesthesiology—Professor of AnesthesiologyNoneNoneNoneNoneNoneNone
Mary G. GeorgeContent Reviewer—HHSCenters for Disease Control and Prevention—Senior Medical Officer, Division for Heart Disease and Stroke PreventionNoneNoneNoneNoneNoneNone
Linda D. GillamContent Reviewer—ACC Cardiovascular Imaging Section Leadership CouncilMorristown Medical Center—Professor of Cardiology; Vice Chair, Cardiovascular MedicineNoneNoneNoneNoneNoneNone
Robert A. GuytonContent Reviewer—ACC/AHA Task Force on Practice GuidelinesEmory Clinic—Professor and Chief, Division of Cardiothoracic Surgery

Medtronic

NoneNoneNoneNoneNone
Joerg HerrmannContent Reviewer—ACC Interventional Section Leadership CouncilMayo Medical School—Internal Medicine and Cardiovascular DiseaseNoneNoneNoneNoneNoneNone
Judith S. HochmanContent Reviewer—ACC/AHA Task Force on Practice GuidelinesNew York University School of Medicine, Division of Cardiology—Clinical Chief of Cardiology

GlaxoSmithKline

Janssen Pharmaceuticals

NoneNoneNoneNoneNone
Yuling HongContent Reviewer—HHSCenters for Disease Control and Prevention—Associate DirectorNoneNoneNoneNoneNoneNone
Lloyd W. KleinContent Reviewer—ACC Interventional Section Leadership CouncilRush Medical College—Professor of MedicineNoneNoneNoneNoneNoneNone
Frederick G. KushnerContent ReviewerTulane University School of Medicine—Clinical Professor of Medicine; Heart Clinic of Louisiana—Medical DirectorNoneNoneNoneNoneNoneNone
Ehtisham MahmudContent Reviewer—ACC Interventional Section Leadership CouncilUniversity of California, San Diego—Professor of Medicine/Cardiology,
Chief of Cardiovascular Medicine; Director, Interventional Cardiology and Cardiovascular Catheterization Laboratory

Abiomed

Cordis

Eli Lilly

Gilead

Johnson & Johnson

Medtronic

Eli Lilly

Medtronic

None

Abbott Vascular

Accumetrics

Merck Schering-Plough

Boston Scientific

Gilead

The Medicines Company

Sanofi-aventis

NoneNone
Carlos Martínez-SánchezContent Reviewer—AIGCardiology Society of Mexico—PresidentNoneNoneNone

AstraZeneca

Eli Lilly

Sanofi-aventis

NoneNone
L. Kristen NewbyContent ReviewerDuke University Medical Center—Associate Professor of Clinical Medicine

Johnson & Johnson

Daiichi-Sankyo

NoneNone

Amylin

AstraZeneca

Bristol-Myers Squibb

Eli Lilly

GlaxoSmithKline

Merck

NoneNone
Patrick T. O’GaraContent ReviewerBrigham and Women’s Hospital—Professor of Medicine, Harvard Medical School; Director, Clinical CardiologyNoneNoneNoneNoneNoneNone
Narith OuContent ReviewerMayo Clinic—Pharmacotherapy Coordinator, Pharmacy ServicesNoneNoneNoneNoneNoneNone
Gurusher S. PanjrathContent Reviewer—ACC Heart Failure and Transplant Section Leadership CouncilGeorge Washington Medical Faculty Associates—Assistant Professor of Medicine; Director of Heart Failure and Mechanical Support ProgramNoneNoneNoneNoneNoneNone
Rajan PatelContent Reviewer—ACC Cardiovascular Imaging Section Leadership CouncilOchsner Clinic Foundation—Interventional CardiologistNoneNoneNoneNoneNoneNone
Carl J. PepineContent ReviewerShands Hospital at University of Florida—Professor and Chief, Division of Cardiovascular Medicine

Lilly/Cleveland Clinic (DSMB)

NoneNone

AstraZeneca

Gilead Sciences

Park-Davis

Pfizer

Sanofi-aventis

NoneNone
Sunil V. RaoContent Reviewer—ACC Interventional Section Leadership CouncilDuke University Medical Center—Associate Professor of Medicine

AstraZeneca

Daiichi-Sankyo

Eli Lilly

Terumo Medical

The Medicines Company

NoneNone

Sanofi-aventis

Abbott Vascular

None
Pasala S. RavichandranContent Reviewer—ACC Surgeons’ Scientific CouncilOregon Health and Science University—Associate ProfessorNoneNoneNoneNoneNoneNone
Michael W. RichContent ReviewerWashington University School of Medicine—Professor of MedicineNoneNoneNoneNoneNoneNone
Frank W. SellkeContent Reviewer—ACC/AHA Task Force on Practice GuidelinesBrown Medical School, Rhode Island Hospital—Professor; Chief of Cardiothoracic SurgeryNoneNoneNoneNoneNoneNone
Alan WuContent Reviewer—AACCSan Francisco General Hospital and Trauma Center—Chief, Clinical Chemistry Laboratory

Abbott

Singulex

NoneNoneNoneNoneNone

This table represents the relationships of reviewers with industry and other entities that were disclosed at the time of peer review and determined to be relevant to this document. It does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of ≥5% of the voting stock or share of the business entity, or ownership of ≥$10,000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person’s gross income for the previous year. A relationship is considered to be modest if it is less than significant under the preceding definition. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. Names are listed in alphabetical order within each category of review.

According to the ACC/AHA, a person has a relevant relationship IF: a) the relationship or interest relates to the same or similar subject matter, intellectual property or asset, topic, or issue addressed in the document; or b) the company/entity (with whom the relationship exists) makes a drug, drug class, or device addressed in the document, or makes a competing drug or device addressed in the document; or c) the person or a member of the person’s household, has a reasonable potential for financial, professional or other personal gain or loss as a result of the issues/content addressed in the document.

AAAHC indicates Accreditation Association for Ambulatory Health Care; AACC, American Association for Clinical Chemistry; AAFP, American Academy of Family Physicians; AHA, American Heart Association; AIG, Association of International Governors; BMS, Bristol-Myers Squibb; DCRI, Duke Clinical Research Institute; DSMB, data safety monitoring board; HHS, Health and Human Services; NHLBI, National Heart, Lung, and Blood Institute; NIH, National Institutes of Health; SCAI, Society for Cardiovascular Angiography and Interventions; STS, Society of Thoracic Surgeons; TIMI, Thrombolysis In Myocardial Infarction; and VA, Veterans Affairs.

∗ Significant relationship.

† No financial benefit.

  • 1. Committee on Standards for Developing Trustworthy Clinical Practice Guidelines; Institute of Medicine : Clinical Practice Guidelines We Can Trust . Washington, DC: The National Academies Press2011.

    Google Scholar
  • 2. Committee on Standards for Systematic Reviews of Comparative Effectiveness Research, Institute of Medicine : Finding What Works in Health Care: Standards for Systematic Reviews . Washington, DC: The National Academies Press2011.

    Google Scholar
  • 3. Jacobs A.K., Kushner F.G., Ettinger S.M.et al. : "ACCF/AHA clinical practice guideline methodology summit report: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol 2013; 61: 213.

    View ArticleGoogle Scholar
  • 4. Jacobs A.K., Anderson J.L. and Halperin J.L. : "The evolution and future of ACC/AHA clinical practice guidelines: a 30-year journey". J Am Coll Cardiol 2014; 64: 1373.

    View ArticleGoogle Scholar
  • 5. Anderson J.L., Heidenreich P.A., Barnett P.G.et al. : "ACC/AHA statement on cost/value methodology in clinical practice guidelines and performance measures: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and Task Force on Practice Guidelines". J Am Coll Cardiol 2014; 63: 2304.

    View ArticleGoogle Scholar
  • 6. ACC/AHA Task Force on Practice Guidelines. Methodology Manual and Policies From the ACCF/AHA Task Force on Practice Guidelines. Available at: http://assets.cardiosource.com/Methodology_Manual_for_ACC_AHA_Writing_Committees.pdf and http://my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/documents/downloadable/ucm_319826.pdf. Accessed April 9, 2014.

    Google Scholar
  • 7. Arnett D.K., Goodman R.A., Halperin J.L., Anderson J.L., Parekh A.K. and Zoghbi W.A. : "AHA/ACC/HHS strategies to enhance application of clinical practice guidelines in patients with cardiovascular disease and comorbid conditions: from the American Heart Association, American College of Cardiology, and U.S. Department of Health and Human Services.". J Am Coll Cardiol 2014; 60: 1851.

    Google Scholar
  • 8. Amsterdam E.A., Wenger N.K., Brindis R.G.et al. : "2014 ACC/AHA guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol 2014; 64: e139.

    View ArticleGoogle Scholar
  • 9. Jneid H., Anderson J.L., Wright R.S.et al. : "2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol 2012; 60: 645.

    View ArticleGoogle Scholar
  • 10. Go A.S., Mozaffarian D., Roger V.L.et al. : "Heart Disease and Stroke Statistics–2013 Update: a report from the American Heart Association". Circulation 2013; 127: e6.

    MedlineGoogle Scholar
  • 11. Fihn S., Blankenship J.C., Alexander K.P.et al. : "2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease". J Am Coll Cardiol 2014; 64: 1929.

    View ArticleGoogle Scholar
  • 12. Fihn S.D., Gardin J.M., Abrams J.et al. : "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons". J Am Coll Cardiol 2012; 60: e44.

    View ArticleGoogle Scholar
  • 13. January C.T., Wann L.S., Alpert J.S.et al. : "2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society". J Am Coll Cardiol 2014; 64: e1.

    View ArticleGoogle Scholar
  • 14. Goff D.C., Lloyd-Jones D.M., Bennett G.et al. : "2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol 2014; 63: 2935.

    View ArticleGoogle Scholar
  • 15. Yancy C.W., Jessup M., Bozkurt B.et al. : "2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol 2013; 62: e147.

    View ArticleGoogle Scholar
  • 16. Eckel R.H., Jakicic J.M., Ard J.D.et al. : "2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol 2014; 63: 2960.

    View ArticleGoogle Scholar
  • 17. Jensen M.D., Ryan D.H., Apovian C.M.et al. : "2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Obesity Society". J Am Coll Cardiol 2014; 63: 2985.

    View ArticleGoogle Scholar
  • 18. O'Gara P.T., Kushner F.G., Ascheim D.D.et al. : "2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol 2013; 61: e78.

    View ArticleGoogle Scholar
  • 19. Stone N.J., Robinson J., Lichtenstein A.H.et al. : "2014 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol 2014; 63: 2889.

    View ArticleGoogle Scholar
  • 20. Steg P.G., James S.K., Atar D.et al. : "ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology (ESC)". Eur Heart J 2012; 33: 2569.

    CrossrefMedlineGoogle Scholar
  • 21. Epstein A.E., Dimarco J.P., Ellenbogen K.A.et al. : "2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society". J Am Coll Cardiol 2013; 61: e6.

    View ArticleGoogle Scholar
  • 22. Thygesen K., Alpert J.S., Jaffe A.S.et al. : "Third universal definition of myocardial infarction". J Am Coll Cardiol 2012; 60: 1581.

    View ArticleGoogle Scholar
  • 23. Hamm C.W., Bassand J.P., Agewall S.et al. : "ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the Management of acute coronary syndromes (ACS) in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)". Eur Heart J 2011; 32: 2999.

    CrossrefMedlineGoogle Scholar
  • 24. Hillis L.D., Smith P.K., Anderson J.L.et al. : "2011 ACCF/AHA guideline for coronary artery bypass graft surgery. a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons". J Am Coll Cardiol 2011; 58: e123.

    View ArticleGoogle Scholar
  • 25. Gersh B.J., Maron B.J., Bonow R.O.et al. : "2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons". J Am Coll Cardiol 2011; 58: e212.

    View ArticleGoogle Scholar
  • 26. Mosca L., Benjamin E.J., Berra K.et al. : "Effectiveness-based guidelines for the prevention of cardiovascular disease in women–2011 update: a guideline from the American Heart Association". J Am Coll Cardiol 2011; 57: 1404.

    View ArticleGoogle Scholar
  • 27. Levine G.N., Bates E.R., Blankenship J.C.et al. : "2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions". J Am Coll Cardiol 2011; 58: e44.

    View ArticleGoogle Scholar
  • 28. Smith S.C., Benjamin E.J., Bonow R.O.et al. : "AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation". J Am Coll Cardiol 2011; 58: 2432.

    View ArticleGoogle Scholar
  • 29. Greenland P., Alpert J.S., Beller G.A.et al. : "2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol 2010; 56: e50.

    View ArticleGoogle Scholar
  • 30. Wijns W., Kolh P., Danchin N.et al. : "Guidelines on myocardial revascularization". Eur Heart J 2010; 31: 2501.

    CrossrefMedlineGoogle Scholar
  • 31. National Clinical Guideline Centre (UK). Unstable angina and NSTEMI: the early management of unstable angina and non-ST-segment-elevation myocardial infarction. Available at: https://www.nice.org.uk/guidance/cg94/resources/guidance-unstable-angina-and-nstemi-pdf. Accessed September 22, 2014.

    Google Scholar
  • 32. Peberdy M.A., Callaway C.W., Neumar R.W.et al. : "Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation 2010; 122: S768.

    CrossrefMedlineGoogle Scholar
  • 33. Chobanian A.V., Bakris G.L., Black H.R.et al. : "The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report". JAMA 2003; 289: 2560.

    CrossrefMedlineGoogle Scholar
  • 34. Cannon C.P., Brindis R.G., Chaitman B.R.et al. : "2013 ACCF/AHA key data elements and definitions for measuring the clinical management and outcomes of patients with acute coronary syndromes and coronary artery disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Acute Coronary Syndromes and Coronary Artery Disease Clinical Data Standards)". J Am Coll Cardiol 2013; 61: 992.

    View ArticleGoogle Scholar
  • 35. Newby L.K., Jesse R.L., Babb J.D.et al. : "ACCF 2012 expert consensus document on practical clinical considerations in the interpretation of troponin elevations: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents". J Am Coll Cardiol 2012; 60: 2427.

    View ArticleGoogle Scholar
  • 36. Amsterdam E.A., Kirk J.D., Bluemke D.A.et al. : "Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association". Circulation 2010; 122: 1756.

    CrossrefMedlineGoogle Scholar
  • 37. Buse J.B., Ginsberg H.N., Bakris G.L.et al. : "Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association". Diabetes Care 2007; 30: 162.

    CrossrefMedlineGoogle Scholar
  • 38. Harper S.A., Fukuda K., Uyeki T.M.et al. : "Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR Recomm Rep 2005; 54: 1.

    MedlineGoogle Scholar
  • 39. Libby P. : "Current concepts of the pathogenesis of the acute coronary syndromes". Circulation 2001; 104: 365.

    CrossrefMedlineGoogle Scholar
  • 40. Antman E.M., Cohen M., Bernink P.J.et al. : "The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making". JAMA 2000; 284: 835.

    CrossrefMedlineGoogle Scholar
  • 41. Boersma E., Pieper K.S., Steyerberg E.W.et al. : "Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators". Circulation 2000; 101: 2557.

    CrossrefMedlineGoogle Scholar
  • 42. Granger C.B., Goldberg R.J., Dabbous O.et al. : "Predictors of hospital mortality in the Global Registry of Acute Coronary Events". Arch Intern Med 2003; 163: 2345.

    CrossrefMedlineGoogle Scholar
  • 43. Keller T., Zeller T., Ojeda F.et al. : "Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction". JAMA 2011; 306: 2684.

    CrossrefMedlineGoogle Scholar
  • 44. Eggers K.M., Jaffe A.S., Venge P.et al. : "Clinical implications of the change of cardiac troponin I levels in patients with acute chest pain - an evaluation with respect to the Universal Definition of Myocardial Infarction". Clin Chim Acta 2011; 412: 91.

    CrossrefMedlineGoogle Scholar
  • 45. Giannitsis E., Becker M., Kurz K.et al. : "High-sensitivity cardiac troponin T for early prediction of evolving non-ST-segment elevation myocardial infarction in patients with suspected acute coronary syndrome and negative troponin results on admission". Clin Chem 2010; 56: 642.

    CrossrefMedlineGoogle Scholar
  • 46. Lindahl B., Venge P. and James S. : "The new high-sensitivity cardiac troponin T assay improves risk assessment in acute coronary syndromes". Am Heart J 2010; 160: 224.

    CrossrefMedlineGoogle Scholar
  • 47. Reichlin T., Irfan A., Twerenbold R.et al. : "Utility of absolute and relative changes in cardiac troponin concentrations in the early diagnosis of acute myocardial infarction". Circulation 2011; 124: 136.

    CrossrefMedlineGoogle Scholar
  • 48. Apple F.S., Smith S.W., Pearce L.A.et al. : "Delta changes for optimizing clinical specificity and 60-day risk of adverse events in patients presenting with symptoms suggestive of acute coronary syndrome utilizing the ADVIA Centaur TnI-Ultra assay". Clin Biochem 2012; 45: 711.

    CrossrefMedlineGoogle Scholar
  • 49. Santalo M., Martin A., Velilla J.et al. : "Using high- sensitivity troponin T: the importance of the proper gold standard". Am J Med 2013; 126: 709.

    CrossrefMedlineGoogle Scholar
  • 50. Apple F.S., Pearce L.A., Smith S.W.et al. : "Role of monitoring changes in sensitive cardiac troponin I assay results for early diagnosis of myocardial infarction and prediction of risk of adverse events". Clin Chem 2009; 55: 930.

    CrossrefMedlineGoogle Scholar
  • 51. Hammarsten O., Fu M.L., Sigurjonsdottir R.et al. : "Troponin T percentiles from a random population sample, emergency room patients and patients with myocardial infarction". Clin Chem 2012; 58: 628.

    CrossrefMedlineGoogle Scholar
  • 52. Pollack C.V., Sites F.D., Shofer F.S.et al. : "Application of the TIMI risk score for unstable angina and non-ST elevation acute coronary syndrome to an unselected emergency department chest pain population". Acad Emerg Med 2006; 13: 13.

    CrossrefMedlineGoogle Scholar
  • 53. Go J., Narmi A., Sype J.et al. : "Impact of renal dysfunction on the prognostic value of the TIMI risk score in patients with non-ST elevation acute coronary syndrome". Coron Artery Dis 2011; 22: 411.

    CrossrefMedlineGoogle Scholar
  • 54. Huynh T., Nasmith J., Luong T.M.et al. : "Complementary prognostic values of ST segment deviation and Thrombolysis In Myocardial Infarction (TIMI) risk score in non-ST elevation acute coronary syndromes: Insights from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study". Can J Cardiol 2009; 25: e417.

    CrossrefMedlineGoogle Scholar
  • 55. Eagle K.A., Lim M.J., Dabbous O.H.et al. : "A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry". JAMA 2004; 291: 2727.

    CrossrefMedlineGoogle Scholar
  • 56. Abu-Assi E., Ferreira-Gonzalez I., Ribera A.et al. : "“Do GRACE (Global Registry of Acute Coronary events) risk scores still maintain their performance for predicting mortality in the era of contemporary management of acute coronary syndromes?”". Am Heart J 2010; 160: 826.

    CrossrefMedlineGoogle Scholar
  • 57. Meune C., Drexler B., Haaf P.et al. : "The GRACE score's performance in predicting in-hospital and 1-year outcome in the era of high-sensitivity cardiac troponin assays and B-type natriuretic peptide". Heart 2011; 97: 1479.

    CrossrefMedlineGoogle Scholar
  • 58. Eggers K.M., Kempf T., Venge P.et al. : "Improving long-term risk prediction in patients with acute chest pain: the Global Registry of Acute Coronary Events (GRACE) risk score is enhanced by selected nonnecrosis biomarkers". Am Heart J 2010; 160: 88.

    Google Scholar
  • 59. Matetzky S., Freimark D., Feinberg M.S.et al. : "Acute myocardial infarction with isolated ST-segment elevation in posterior chest leads V7-9: “hidden” ST-segment elevations revealing acute posterior infarction". J Am Coll Cardiol 1999; 34: 748.

    View ArticleGoogle Scholar
  • 60. Boden W.E., Kleiger R.E., Gibson R.S.et al. : "Electrocardiographic evolution of posterior acute myocardial infarction: importance of early precordial ST-segment depression". Am J Cardiol 1987; 59: 782.

    CrossrefMedlineGoogle Scholar
  • 61. Zalenski R.J., Rydman R.J., Sloan E.P.et al. : "Value of posterior and right ventricular leads in comparison to the standard 12-lead electrocardiogram in evaluation of ST-segment elevation in suspected acute myocardial infarction". Am J Cardiol 1997; 79: 1579.

    CrossrefMedlineGoogle Scholar
  • 62. Selker H.P., Zalenski R.J., Antman E.M.et al. : "An evaluation of technologies for identifying acute cardiac ischemia in the emergency department: a report from a National Heart Attack Alert Program Working Group". Ann Emerg Med 1997; 29: 13.

    CrossrefMedlineGoogle Scholar
  • 63. Fesmire F.M., Percy R.F., Bardoner J.B.et al. : "Usefulness of automated serial 12-lead ECG monitoring during the initial emergency department evaluation of patients with chest pain". Ann Emerg Med 1998; 31: 3.

    CrossrefMedlineGoogle Scholar
  • 64. Haaf P., Reichlin T., Corson N.et al. : "B-type natriuretic peptide in the early diagnosis and risk stratification of acute chest pain". Am J Med 2011; 124: 444.

    CrossrefGoogle Scholar
  • 65. Brown A.M., Sease K.L., Robey J.L.et al. : "The impact of B-type natriuretic peptide in addition to troponin I, creatine kinase-MB, and myoglobin on the risk stratification of emergency department chest pain patients with potential acute coronary syndrome". Ann Emerg Med 2007; 49: 153.

    MedlineGoogle Scholar
  • 66. Heeschen C., Hamm C.W., Mitrovic V.et al. : "N-terminal pro-B-type natriuretic peptide levels for dynamic risk stratification of patients with acute coronary syndromes". Circulation 2004; 110: 3206.

    CrossrefMedlineGoogle Scholar
  • 67. Morrow D.A., de Lemos J.A., Sabatine M.S.et al. : "Evaluation of B-type natriuretic peptide for risk assessment in unstable angina/non-ST-elevation myocardial infarction: B-type natriuretic peptide and prognosis in TACTICS-TIMI 18". J Am Coll Cardiol 2003; 41: 1264.

    View ArticleGoogle Scholar
  • 68. James S.K., Lindback J., Tilly J.et al. : "Troponin-T and N-terminal pro-B-type natriuretic peptide predict mortality benefit from coronary revascularization in acute coronary syndromes: a GUSTO-IV substudy". J Am Coll Cardiol 2006; 48: 1146.

    View ArticleGoogle Scholar
  • 69. Deleted in press.

    Google Scholar
  • 70. Kavsak P.A., MacRae A.R., Lustig V.et al. : "The impact of the ESC/ACC redefinition of myocardial infarction and new sensitive troponin assays on the frequency of acute myocardial infarction". Am Heart J 2006; 152: 118.

    CrossrefMedlineGoogle Scholar
  • 71. Goodman S.G., Steg P.G., Eagle K.A.et al. : "The diagnostic and prognostic impact of the redefinition of acute myocardial infarction: lessons from the Global Registry of Acute Coronary Events (GRACE)". Am Heart J 2006; 151: 654.

    CrossrefMedlineGoogle Scholar
  • 72. Amodio G., Antonelli G., Varraso L.et al. : "Clinical impact of the troponin 99th percentile cut-off and clinical utility of myoglobin measurement in the early management of chest pain patients admitted to the Emergency Cardiology Department". Coron Artery Dis 2007; 18: 181.

    CrossrefGoogle Scholar
  • 73. Takakuwa K.M., Ou F.S., Peterson E.D.et al. : "The usage patterns of cardiac bedside markers employing point-of-care testing for troponin in non-ST-segment elevation acute coronary syndrome: results from CRUSADE". Clin Cardiol 2009; 32: 498.

    Google Scholar
  • 74. Ie E.H., Klootwijk P.J., Weimar W.et al. : "Significance of acute versus chronic troponin T elevation in dialysis patients". Nephron Clin Pract 2004; 98: c87.

    CrossrefGoogle Scholar
  • 75. MacRae A.R., Kavsak P.A., Lustig V.et al. : "Assessing the requirement for the 6-hour interval between specimens in the American Heart Association Classification of Myocardial Infarction in Epidemiology and Clinical Research Studies". Clin Chem 2006; 52: 812.

    CrossrefMedlineGoogle Scholar
  • 76. Kontos M.C., de Lemos J.A., Ou F.S.et al. : "Troponin-positive, MB-negative patients with non-ST-elevation myocardial infarction: an undertreated but high-risk patient group: Results from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network-Get With The Guidelines (NCDR ACTION-GWTG) Registry". Am Heart J 2010; 160: 819.

    CrossrefMedlineGoogle Scholar
  • 77. Aviles R.J., Wright R.S., Aviles J.M.et al. : "Long-term prognosis of patients with clinical unstable angina pectoris without elevation of creatine kinase but with elevation of cardiac troponin i levels". Am J Cardiol 2002; 90: 875.

    CrossrefGoogle Scholar
  • 78. Eggers K.M., Oldgren J., Nordenskjold A.et al. : "Diagnostic value of serial measurement of cardiac markers in patients with chest pain: limited value of adding myoglobin to troponin I for exclusion of myocardial infarction". Am Heart J 2004; 148: 574.

    CrossrefMedlineGoogle Scholar
  • 79. Volz K.A., McGillicuddy D.C., Horowitz G.L.et al. : "Creatine kinase-MB does not add additional benefit to a negative troponin in the evaluation of chest pain". Am J Emerg Med 2012; 30: 188.

    CrossrefGoogle Scholar
  • 80. Newby L.K., Roe M.T., Chen A.Y.et al. : "Frequency and clinical implications of discordant creatine kinase-MB and troponin measurements in acute coronary syndromes". J Am Coll Cardiol 2006; 47: 312.

    View ArticleGoogle Scholar
  • 81. Kavsak P.A., MacRae A.R., Newman A.M.et al. : "Effects of contemporary troponin assay sensitivity on the utility of the early markers myoglobin and CKMB isoforms in evaluating patients with possible acute myocardial infarction". Clin Chim Acta 2007; 380: 213.

    CrossrefGoogle Scholar
  • 82. Giannitsis E., Steen H., Kurz K.et al. : "Cardiac magnetic resonance imaging study for quantification of infarct size comparing directly serial versus single time-point measurements of cardiac troponin T". J Am Coll Cardiol 2008; 51: 307.

    View ArticleGoogle Scholar
  • 83. Younger J.F., Plein S., Barth J.et al. : "Troponin-I concentration 72 h after myocardial infarction correlates with infarct size and presence of microvascular obstruction". Heart 2007; 93: 1547.

    CrossrefMedlineGoogle Scholar
  • 84. Bonaca M., Scirica B., Sabatine M.et al. : "Prospective evaluation of the prognostic implications of improved assay performance with a sensitive assay for cardiac troponin I". J Am Coll Cardiol 2010; 55: 2118.

    View ArticleGoogle Scholar
  • 85. de Lemos J.A., Morrow D.A., Bentley J.H.et al. : "The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes". N Engl J Med 2001; 345: 1014.

    CrossrefMedlineGoogle Scholar
  • 86. Weber M., Bazzino O., Navarro Estrada J.L.et al. : "N-terminal B-type natriuretic peptide assessment provides incremental prognostic information in patients with acute coronary syndromes and normal troponin T values upon admission". J Am Coll Cardiol 2008; 51: 1188.

    View ArticleGoogle Scholar
  • 87. Heeschen C., Hamm C.W., Bruemmer J.et al. : "Predictive value of C-reactive protein and troponin T in patients with unstable angina: a comparative analysis. CAPTURE Investigators. Chimeric c7E3 AntiPlatelet Therapy in Unstable angina REfractory to standard treatment trial". J Am Coll Cardiol 2000; 35: 1535.

    View ArticleGoogle Scholar
  • 88. Kilcullen N., Viswanathan K., Das R.et al. : "Heart-type fatty acid-binding protein predicts long-term mortality after acute coronary syndrome and identifies high-risk patients across the range of troponin values". J Am Coll Cardiol 2007; 50: 2061.

    View ArticleGoogle Scholar
  • 89. Wollert K.C., Kempf T., Lagerqvist B.et al. : "Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST-elevation acute coronary syndrome". Circulation 2007; 116: 1540.

    CrossrefMedlineGoogle Scholar
  • 90. Aviles R.J., Askari A.T., Lindahl B.et al. : "Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction". N Engl J Med 2002; 346: 2047.

    CrossrefMedlineGoogle Scholar
  • 91. Apple F.S., Christenson R.H., Valdes R.et al. : "Simultaneous rapid measurement of whole blood myoglobin, creatine kinase MB, and cardiac troponin I by the triage cardiac panel for detection of myocardial infarction". Clin Chem 1999; 45: 199.

    CrossrefMedlineGoogle Scholar
  • 92. Kleiman N.S., Lakkis N., Cannon C.P.et al. : "Prospective analysis of creatine kinase muscle-brain fraction and comparison with troponin T to predict cardiac risk and benefit of an invasive strategy in patients with non-ST-elevation acute coronary syndromes". J Am Coll Cardiol 2002; 40: 1044.

    View ArticleGoogle Scholar
  • 93. Farkouh M.E., Smars P.A., Reeder G.S.et al. : "A clinical trial of a chest-pain observation unit for patients with unstable angina. Chest Pain Evaluation in the Emergency Room (CHEER) Investigators". N Engl J Med 1998; 339: 1882.

    CrossrefMedlineGoogle Scholar
  • 94. Gomez M.A., Anderson J.L., Karagounis L.A.et al. : "An emergency department-based protocol for rapidly ruling out myocardial ischemia reduces hospital time and expense: results of a randomized study (ROMIO)". J Am Coll Cardiol 1996; 28: 25.

    View ArticleGoogle Scholar
  • 95. Amsterdam E.A., Kirk J.D., Diercks D.B.et al. : "Immediate exercise testing to evaluate low-risk patients presenting to the emergency department with chest pain". J Am Coll Cardiol 2002; 40: 251.

    View ArticleGoogle Scholar
  • 96. Trippi J.A. and Lee K.S. : "Dobutamine stress tele-echocardiography as a clinical service in the emergency department to evaluate patients with chest pain". Echocardiography 1999; 16: 179.

    CrossrefGoogle Scholar
  • 97. Bholasingh R., Cornel J.H., Kamp O.et al. : "Prognostic value of predischarge dobutamine stress echocardiography in chest pain patients with a negative cardiac troponin T". J Am Coll Cardiol 2003; 41: 596.

    View ArticleGoogle Scholar
  • 98. Hoffmann U., Truong Q.A., Schoenfeld D.A.et al. : "Coronary CT angiography versus standard evaluation in acute chest pain". N Engl J Med 2012; 367: 299.

    CrossrefMedlineGoogle Scholar
  • 99. Litt H.I., Gatsonis C., Snyder B.et al. : "CT angiography for safe discharge of patients with possible acute coronary syndromes". N Engl J Med 2012; 366: 1393.

    CrossrefMedlineGoogle Scholar
  • 100. Hoffmann U., Bamberg F., Chae C.U.et al. : "Coronary computed tomography angiography for early triage of patients with acute chest pain: the ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) trial". J Am Coll Cardiol 2009; 53: 1642.

    View ArticleGoogle Scholar
  • 101. Udelson J.E., Beshansky J.R., Ballin D.S.et al. : "Myocardial perfusion imaging for evaluation and triage of patients with suspected acute cardiac ischemia: a randomized controlled trial". JAMA 2002; 288: 2693.

    CrossrefMedlineGoogle Scholar
  • 102. Kontos M.C., Jesse R.L., Schmidt K.L.et al. : "Value of acute rest sestamibi perfusion imaging for evaluation of patients admitted to the emergency department with chest pain". J Am Coll Cardiol 1997; 30: 976.

    View ArticleGoogle Scholar
  • 103. Goldstein R.E., Rosing D.R., Redwood D.R.et al. : "Clinical and circulatory effects of isosorbide dinitrate. Comparison with nitroglycerin". Circulation 1971; 43: 629.

    CrossrefMedlineGoogle Scholar
  • 104. Bassan M.M. : "The daylong pattern of the antianginal effect of long-term three times daily administered isosorbide dinitrate". J Am Coll Cardiol 1990; 16: 936.

    View ArticleGoogle Scholar
  • 105. Kohli R.S., Rodrigues E.A., Kardash M.M.et al. : "Acute and sustained effects of isosorbide 5-mononitrate in stable angina pectoris". Am J Cardiol 1986; 58: 727.

    Google Scholar
  • 106. Kaplan K., Davison R., Parker M.et al. : "Intravenous nitroglycerin for the treatment of angina at rest unresponsive to standard nitrate therapy". Am J Cardiol 1983; 51: 694.

    CrossrefMedlineGoogle Scholar
  • 107. Melandri G., Branzi A., Tartagni F.et al. : "Haemodynamic effects of metoprolol and intravenous nitroglycerin versus metoprolol alone in patients with acute myocardial infarction". Eur Heart J 1987; 8: 592.

    Google Scholar
  • 108. Yusuf S., Collins R., MacMahon S.et al. : "Effect of intravenous nitrates on mortality in acute myocardial infarction: an overview of the randomised trials". Lancet 1988; 1: 1088.

    CrossrefMedlineGoogle Scholar
  • 109. Charvat J., Kuruvilla T. and al A.H. : "Beneficial effect of intravenous nitroglycerin in patients with non-Q myocardial infarction". Cardiologia 1990; 35: 49.

    Google Scholar
  • 110. Karlberg K.E., Saldeen T., Wallin R.et al. : "Intravenous nitroglycerin reduces ischaemia in unstable angina pectoris: a double-blind placebo-controlled study". J Intern Med 1998; 243: 25.

    CrossrefMedlineGoogle Scholar
  • 111. Peacock W.F., Emerman C.L. and Young J. : "Nesiritide in congestive heart failure associated with acute coronary syndromes: a pilot study of safety and efficacy". J Card Fail 2004; 10: 120.

    CrossrefGoogle Scholar
  • 112. Cheitlin M.D., Hutter A.M., Brindis R.G.et al. : "Use of sildenafil (Viagra) in patients with cardiovascular disease. Technology and Practice Executive Committee". Circulation 1999; 99: 168.

    MedlineGoogle Scholar
  • 113. Webb D.J., Freestone S., Allen M.J.et al. : "Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist". Am J Cardiol 1999; 83: 21C.

    CrossrefMedlineGoogle Scholar
  • 114. Kloner R.A., Hutter A.M., Emmick J.T.et al. : "Time course of the interaction between tadalafil and nitrates". J Am Coll Cardiol 2003; 42: 1855.

    View ArticleGoogle Scholar
  • 115. Meine T.J., Roe M.T., Chen A.Y.et al. : "Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative". Am Heart J 2005; 149: 1043.

    CrossrefMedlineGoogle Scholar
  • 116. Iakobishvili Z., Cohen E., Garty M.et al. : "Use of intravenous morphine for acute decompensated heart failure in patients with and without acute coronary syndromes". Acute Card Care 2011; 13: 76.

    Google Scholar
  • 117. Gislason G.H., Jacobsen S., Rasmussen J.N.et al. : "Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction". Circulation 2006; 113: 2906.

    CrossrefMedlineGoogle Scholar
  • 118. Kearney P.M., Baigent C., Godwin J.et al. : "Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials". BMJ 2006; 332: 1302.

    CrossrefMedlineGoogle Scholar
  • 119. Roberts R., Rogers W.J., Mueller H.S.et al. : "Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study". Circulation 1991; 83: 422.

    CrossrefMedlineGoogle Scholar
  • 120. Freemantle N., Cleland J., Young P.et al. : "Beta blockade after myocardial infarction: systematic review and meta regression analysis". BMJ 1999; 318: 1730.

    CrossrefMedlineGoogle Scholar
  • 121. Kontos M.C., Diercks D.B., Ho P.M.et al. : "Treatment and outcomes in patients with myocardial infarction treated with acute beta-blocker therapy: results from the American College of Cardiology's NCDR((R))". Am Heart J 2011; 161: 864.

    CrossrefMedlineGoogle Scholar
  • 122. de Peuter O.R., Lussana F., Peters R.J.et al. : "A systematic review of selective and non-selective beta blockers for prevention of vascular events in patients with acute coronary syndrome or heart failure". Neth J Med 2009; 67: 284.

    MedlineGoogle Scholar
  • 123. Chen Z.M., Pan H.C., Chen Y.P.et al. : "Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial". Lancet 2005; 366: 1622.

    CrossrefMedlineGoogle Scholar
  • 124. Gibson R.S., Boden W.E., Theroux P.et al. : "Diltiazem and reinfarction in patients with non-Q-wave myocardial infarction. Results of a double-blind, randomized, multicenter trial". N Engl J Med 1986; 315: 423.

    CrossrefMedlineGoogle Scholar
  • 125. "Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II–DAVIT II)". Am J Cardiol 1990; 66: 779.

    CrossrefMedlineGoogle Scholar
  • 126. Moss A.J., Oakes D., Rubison M.et al. : "Effects of diltiazem on long-term outcome after acute myocardial infarction in patients with and without a history of systemic hypertension. The Multicenter Diltiazem Postinfarction Trial Research Group". Am J Cardiol 1991; 68: 429.

    MedlineGoogle Scholar
  • 127. Furberg C.D., Psaty B.M. and Meyer J.V. : "Nifedipine. Dose-related increase in mortality in patients with coronary heart disease". Circulation 1995; 92: 1326.

    CrossrefMedlineGoogle Scholar
  • 128. "Early treatment of unstable angina in the coronary care unit: a randomised, double blind, placebo controlled comparison of recurrent ischaemia in patients treated with nifedipine or metoprolol or both. Report of the Holland Interuniversity Nifedipine/Metoprolol Trial (HINT) Research Group". Br Heart J 1986; 56: 400.

    CrossrefMedlineGoogle Scholar
  • 129. Cannon C.P., Steinberg B.A., Murphy S.A.et al. : "Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy". J Am Coll Cardiol 2006; 48: 438.

    View ArticleGoogle Scholar
  • 130. Baigent C., Blackwell L., Emberson J.et al. : "Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials". Lancet 2010; 376: 1670.

    CrossrefMedlineGoogle Scholar
  • 131. Cannon C.P., Braunwald E., McCabe C.H.et al. : "Intensive versus moderate lipid lowering with statins after acute coronary syndromes". N Engl J Med 2004; 350: 1495.

    CrossrefMedlineGoogle Scholar
  • 132. Sacks F.M., Pfeffer M.A., Moye L.A.et al. : "The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators". N Engl J Med 1996; 335: 1001.

    CrossrefMedlineGoogle Scholar
  • 133. Cannon C.P., McCabe C.H., Belder R.et al. : "Design of the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT)-TIMI 22 trial". Am J Cardiol 2002; 89: 860.

    CrossrefMedlineGoogle Scholar
  • 134. Garg R. and Yusuf S. : "Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials". JAMA 1995; 273: 1450.

    CrossrefMedlineGoogle Scholar
  • 135. Yusuf S., Sleight P., Pogue J.et al. : "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators". N Engl J Med 2000; 342: 145.

    CrossrefMedlineGoogle Scholar
  • 136. Pfeffer M.A., McMurray J.J., Velazquez E.J.et al. : "Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both". N Engl J Med 2003; 349: 1893.

    CrossrefMedlineGoogle Scholar
  • 137. Yusuf S., Teo K.K., Pogue J.et al. : "Telmisartan, ramipril, or both in patients at high risk for vascular events". N Engl J Med 2008; 358: 1547.

    CrossrefMedlineGoogle Scholar
  • 138. Pitt B., Remme W., Zannad F.et al. : "Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction". N Engl J Med 2003; 348: 1309.

    CrossrefMedlineGoogle Scholar
  • 139. Yusuf S., Teo K., Anderson C.et al. : "Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial". Lancet 2008; 372: 1174.

    CrossrefMedlineGoogle Scholar
  • 140. Dagenais G.R., Pogue J., Fox K.et al. : "Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials". Lancet 2006; 368: 581.

    CrossrefMedlineGoogle Scholar
  • 141. Danchin N., Cucherat M., Thuillez C.et al. : "Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials". Arch Intern Med 2006; 166: 787.

    CrossrefMedlineGoogle Scholar
  • 142. Baigent C., Blackwell L., Collins R.et al. : "Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials". Lancet 2009; 373: 1849.

    CrossrefMedlineGoogle Scholar
  • 143. Yusuf S., Zhao F., Mehta S.R.et al. : "Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation". N Engl J Med 2001; 345: 494.

    CrossrefMedlineGoogle Scholar
  • 144. Mahaffey K.W., Wojdyla D.M., Carroll K.et al. : "Ticagrelor compared with clopidogrel by geographic region in the Platelet Inhibition and Patient Outcomes (PLATO) trial". Circulation 2011; 124: 544.

    CrossrefMedlineGoogle Scholar
  • 145. CAPRIE Steering Committee : "A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE)". Lancet 1996; 348: 1329.

    CrossrefMedlineGoogle Scholar
  • 146. Mehta S.R., Bassand J.P., Chrolavicius S.et al. : "Dose comparisons of clopidogrel and aspirin in acute coronary syndromes". N Engl J Med 2010; 363: 930.

    CrossrefMedlineGoogle Scholar
  • 147. Wallentin L., Becker R.C., Budaj A.et al. : "Ticagrelor versus clopidogrel in patients with acute coronary syndromes". N Engl J Med 2009; 361: 1045.

    CrossrefMedlineGoogle Scholar
  • 148. James S.K., Roe M.T., Cannon C.P.et al. : "Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial". BMJ 2011; 342: d3527.

    CrossrefMedlineGoogle Scholar
  • 149. PRISM-PLUS Study Investigators : "Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators". N Engl J Med 1998; 338: 1488.

    CrossrefMedlineGoogle Scholar
  • 150. Giugliano R.P., White J.A., Bode C.et al. : "Early versus delayed, provisional eptifibatide in acute coronary syndromes". N Engl J Med 2009; 360: 2176.

    CrossrefMedlineGoogle Scholar
  • 151. Cohen M., Demers C., Gurfinkel E.P.et al. : "A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group". N Engl J Med 1997; 337: 447.

    CrossrefMedlineGoogle Scholar
  • 152. Ferguson J.J., Califf R.M., Antman E.M.et al. : "Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial". JAMA 2004; 292: 45.

    MedlineGoogle Scholar
  • 153. Antman E.M., McCabe C.H., Gurfinkel E.P.et al. : "Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) 11B trial". Circulation 1999; 100: 1593.

    CrossrefMedlineGoogle Scholar
  • 154. Stone G.W., McLaurin B.T., Cox D.A.et al. : "Bivalirudin for patients with acute coronary syndromes". N Engl J Med 2006; 355: 2203.

    CrossrefMedlineGoogle Scholar
  • 155. Stone G.W., White H.D., Ohman E.M.et al. : "Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial". Lancet 2007; 369: 907.

    CrossrefMedlineGoogle Scholar
  • 156. Mehta S.R., Granger C.B., Eikelboom J.W.et al. : "Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial". J Am Coll Cardiol 2007; 50: 1742.

    View ArticleGoogle Scholar
  • 157. Yusuf S., Mehta S.R., Chrolavicius S.et al. : "Comparison of fondaparinux and enoxaparin in acute coronary syndromes". N Engl J Med 2006; 354: 1464.

    CrossrefMedlineGoogle Scholar
  • 158. Steg P.G., Jolly S.S., Mehta S.R.et al. : "Low-dose vs standard-dose unfractionated heparin for percutaneous coronary intervention in acute coronary syndromes treated with fondaparinux: the FUTURA/OASIS-8 randomized trial". JAMA 2010; 304: 1339.

    MedlineGoogle Scholar
  • 159. Yusuf S., Mehta S.R., Chrolavicius S.et al. : "Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial". JAMA 2006; 295: 1519.

    CrossrefMedlineGoogle Scholar
  • 160. Oler A., Whooley M.A., Oler J.et al. : "Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. A meta-analysis". JAMA 1996; 276: 811.

    CrossrefMedlineGoogle Scholar
  • 161. Theroux P., Ouimet H., McCans J.et al. : "Aspirin, heparin, or both to treat acute unstable angina". N Engl J Med 1988; 319: 1105.

    CrossrefMedlineGoogle Scholar
  • 162. "Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. The RISC Group". Lancet 1990; 336: 827.

    CrossrefMedlineGoogle Scholar
  • 163. Cohen M., Adams P.C., Hawkins L.et al. : "Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group)". Am J Cardiol 1990; 66: 1287.

    CrossrefMedlineGoogle Scholar
  • 164. Cohen M., Adams P.C., Parry G.et al. : "Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group". Circulation 1994; 89: 81.

    CrossrefMedlineGoogle Scholar
  • 165. Holdright D., Patel D., Cunningham D.et al. : "Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina". J Am Coll Cardiol 1994; 24: 39.

    View ArticleGoogle Scholar
  • 166. Gurfinkel E.P., Manos E.J., Mejail R.I.et al. : "Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia". J Am Coll Cardiol 1995; 26: 313.

    View ArticleGoogle Scholar
  • 167. "Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group". Lancet 1994; 343: 311.

    CrossrefMedlineGoogle Scholar
  • 168. "Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction. Results of the TIMI IIIB Trial. Thrombolysis in Myocardial Ischemia". Circulation 1994; 89: 1545.

    CrossrefMedlineGoogle Scholar
  • 169. Shishehbor M.H., Topol E.J., Mukherjee D.et al. : "Outcome of multivessel coronary intervention in the contemporary percutaneous revascularization era". Am J Cardiol 2006; 97: 1585.

    CrossrefMedlineGoogle Scholar
  • 170. Steinhubl S.R., Berger P.B., Mann J.T.et al. : "Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial". JAMA 2002; 288: 2411.

    CrossrefMedlineGoogle Scholar
  • 171. Mehta S.R., Yusuf S., Peters R.J.et al. : "Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study". Lancet 2001; 358: 527.

    CrossrefMedlineGoogle Scholar
  • 172. Wiviott S.D., Braunwald E., McCabe C.H.et al. : "Prasugrel versus clopidogrel in patients with acute coronary syndromes". N Engl J Med 2007; 357: 2001.

    CrossrefMedlineGoogle Scholar
  • 173. Cannon C.P., Weintraub W.S., Demopoulos L.A.et al. : "Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban". N Engl J Med 2001; 344: 1879.

    CrossrefMedlineGoogle Scholar
  • 174. Damman P., Hirsch A., Windhausen F.et al. : "5-year clinical outcomes in the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) trial a randomized comparison of an early invasive versus selective invasive management in patients with non-ST-segment elevation acute coronary syndrome". J Am Coll Cardiol 2010; 55: 858.

    View ArticleGoogle Scholar
  • 175. de Winter R.J., Windhausen F., Cornel J.H.et al. : "Early invasive versus selectively invasive management for acute coronary syndromes". N Engl J Med 2005; 353: 1095.

    CrossrefMedlineGoogle Scholar
  • 176. "Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators". Lancet 1999; 354: 708.

    CrossrefMedlineGoogle Scholar
  • 177. Fox K.A., Poole-Wilson P.A., Henderson R.A.et al. : "Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina". Lancet 2002; 360: 743.

    CrossrefMedlineGoogle Scholar
  • 178. O'Donoghue M., Boden W.E., Braunwald E.et al. : "Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction: a meta-analysis". JAMA 2008; 300: 71.

    CrossrefMedlineGoogle Scholar
  • 179. Starling M.R., Crawford M.H., Kennedy G.T.et al. : "Treadmill exercise tests predischarge and six weeks post-myocardial infarction to detect abnormalities of known prognostic value". Ann Intern Med 1981; 94: 721.

    CrossrefMedlineGoogle Scholar
  • 180. Marwick T.H., Anderson T., Williams M.J.et al. : "Exercise echocardiography is an accurate and cost-efficient technique for detection of coronary artery disease in women". J Am Coll Cardiol 1995; 26: 335.

    View ArticleGoogle Scholar
  • 181. Larsson H., Areskog M., Areskog N.H.et al. : "Should the exercise test (ET) be performed at discharge or one month later after an episode of unstable angina or non-Q-wave myocardial infarction?". Int J Card Imaging 1991; 7: 7.

    CrossrefMedlineGoogle Scholar
  • 182. Nyman I., Larsson H., Areskog M.et al. : "The predictive value of silent ischemia at an exercise test before discharge after an episode of unstable coronary artery disease. RISC Study Group". Am Heart J 1992; 123: 324.

    CrossrefMedlineGoogle Scholar
  • 183. Mahmarian J.J., Shaw L.J., Filipchuk N.G.et al. : "A multinational study to establish the value of early adenosine technetium-99m sestamibi myocardial perfusion imaging in identifying a low-risk group for early hospital discharge after acute myocardial infarction". J Am Coll Cardiol 2006; 48: 2448.

    View ArticleGoogle Scholar
  • 184. Bangalore S. and Faxon D.P. : "Coronary intervention in patients with acute coronary syndrome: does every culprit lesion require revascularization?". Curr Cardiol Rep 2010; 12: 330.

    CrossrefGoogle Scholar
  • 185. Brener S.J., Milford-Beland S., Roe M.T.et al. : "Culprit-only or multivessel revascularization in patients with acute coronary syndromes: an American College of Cardiology National Cardiovascular Database Registry report". Am Heart J 2008; 155: 140.

    CrossrefMedlineGoogle Scholar
  • 186. Brener S.J., Murphy S.A., Gibson C.M.et al. : "Efficacy and safety of multivessel percutaneous revascularization and tirofiban therapy in patients with acute coronary syndromes". Am J Cardiol 2002; 90: 631.

    CrossrefMedlineGoogle Scholar
  • 187. Palmer N.D., Causer J.P., Ramsdale D.R.et al. : "Effect of completeness of revascularization on clinical outcome in patients with multivessel disease presenting with unstable angina who undergo percutaneous coronary intervention". J Invasive Cardiol 2004; 16: 185.

    MedlineGoogle Scholar
  • 188. Shishehbor M.H., Lauer M.S., Singh I.M.et al. : "In unstable angina or non-ST-segment acute coronary syndrome, should patients with multivessel coronary artery disease undergo multivessel or culprit-only stenting?". J Am Coll Cardiol 2007; 49: 849.

    View ArticleGoogle Scholar
  • 189. Zapata G.O., Lasave L.I., Kozak F.et al. : "Culprit-only or multivessel percutaneous coronary stenting in patients with non-ST-segment elevation acute coronary syndromes: one-year follow-up". J Interv Cardiol 2009; 22: 329.

    CrossrefGoogle Scholar
  • 190. Jolly S.S., Pogue J., Haladyn K.et al. : "Effects of aspirin dose on ischaemic events and bleeding after percutaneous coronary intervention: insights from the PCI-CURE study". Eur Heart J 2009; 30: 900.

    CrossrefMedlineGoogle Scholar
  • 191. Popma J.J., Berger P., Ohman E.M.et al. : "Antithrombotic therapy during percutaneous coronary intervention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy". Chest 2004; 126: 576S.

    CrossrefMedlineGoogle Scholar
  • 192. Barnathan E.S., Schwartz J.S., Taylor L.et al. : "Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty". Circulation 1987; 76: 125.

    CrossrefMedlineGoogle Scholar
  • 193. Schomig A., Neumann F.J., Kastrati A.et al. : "A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents". N Engl J Med 1996; 334: 1084.

    CrossrefMedlineGoogle Scholar
  • 194. Steinhubl S.R., Ellis S.G., Wolski K.et al. : "Ticlopidine pretreatment before coronary stenting is associated with sustained decrease in adverse cardiac events: data from the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) Trial". Circulation 2001; 103: 1403.

    CrossrefMedlineGoogle Scholar
  • 195. Steinhubl D.R. and Deal D.B. : "Optimal duration of pretreatment with clopidogrel prior to PCI: data from the CREDO trial". Circulation 2003; 108: I1742. Abstract.

    Google Scholar
  • 196. Gurbel P.A., Bliden K.P., Zaman K.A.et al. : "Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: results of the Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets (CLEAR PLATELETS) study". Circulation 2005; 111: 1153.

    CrossrefMedlineGoogle Scholar
  • 197. Sabatine M.S., Cannon C.P., Gibson C.M.et al. : "Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study". JAMA 2005; 294: 1224.

    CrossrefMedlineGoogle Scholar
  • 198. von Beckerath N., Taubert D., Pogatsa-Murray G.et al. : "Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial". Circulation 2005; 112: 2946.

    CrossrefMedlineGoogle Scholar
  • 199. Siller-Matula J.M., Huber K., Christ G.et al. : "Impact of clopidogrel loading dose on clinical outcome in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis". Heart 2011; 97: 98.

    CrossrefMedlineGoogle Scholar
  • 200. Mangiacapra F., Muller O., Ntalianis A.et al. : "Comparison of 600 versus 300-mg clopidogrel loading dose in patients with ST-segment elevation myocardial infarction undergoing primary coronary angioplasty". Am J Cardiol 2010; 106: 1208.

    CrossrefMedlineGoogle Scholar
  • 201. "Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. The EPILOG Investigators". N Engl J Med 1997; 336: 1689.

    CrossrefMedlineGoogle Scholar
  • 202. Boersma E., Akkerhuis K.M., Theroux P.et al. : "Platelet glycoprotein IIb/IIIa receptor inhibition in non-ST-elevation acute coronary syndromes: early benefit during medical treatment only, with additional protection during percutaneous coronary intervention". Circulation 1999; 100: 2045.

    CrossrefMedlineGoogle Scholar
  • 203. Hamm C.W., Heeschen C., Goldmann B.et al. : "Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study Investigators". N Engl J Med 1999; 340: 1623.

    CrossrefMedlineGoogle Scholar
  • 204. "Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. The EPIC Investigation". N Engl J Med 1994; 330: 956.

    CrossrefMedlineGoogle Scholar
  • 205. Roe M.T., Armstrong P.W., Fox K.A.et al. : "Prasugrel versus clopidogrel for acute coronary syndromes without revascularization". N Engl J Med 2012; 367: 1297.

    CrossrefMedlineGoogle Scholar
  • 206. Valgimigli M., Percoco G., Barbieri D.et al. : "The additive value of tirofiban administered with the high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: the ADVANCE Trial". J Am Coll Cardiol 2004; 44: 14.

    View ArticleGoogle Scholar
  • 207. Kastrati A., Mehilli J., Neumann F.J.et al. : "Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial". JAMA 2006; 295: 1531.

    CrossrefMedlineGoogle Scholar
  • 208. "Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial". Lancet 2000; 356: 2037.

    CrossrefMedlineGoogle Scholar
  • 209. Peters R.J., Mehta S.R., Fox K.A.et al. : "Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study". Circulation 2003; 108: 1682.

    CrossrefMedlineGoogle Scholar
  • 210. Serebruany V.L., Steinhubl S.R., Berger P.B.et al. : "Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials". Am J Cardiol 2005; 95: 1218.

    CrossrefMedlineGoogle Scholar
  • 211. Steinhubl S.R., Bhatt D.L., Brennan D.M.et al. : "Aspirin to prevent cardiovascular disease: the association of aspirin dose and clopidogrel with thrombosis and bleeding". Ann Intern Med 2009; 150: 379.

    CrossrefMedlineGoogle Scholar
  • 212. Patrono C., Baigent C., Hirsh J.et al. : "Antiplatelet drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)". Chest 2008; 133: 199S.

    CrossrefMedlineGoogle Scholar
  • 213. De Luca G., Cassetti E., Verdoia M.et al. : "Bivalirudin as compared to unfractionated heparin among patients undergoing coronary angioplasty: a meta-analyis of randomised trials". Thromb Haemost 2009; 102: 428.

    CrossrefMedlineGoogle Scholar
  • 214. Lincoff A.M., Bittl J.A., Kleiman N.S.et al. : "Comparison of bivalirudin versus heparin during percutaneous coronary intervention (the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events [REPLACE]-1 trial)". Am J Cardiol 2004; 93: 1092.

    CrossrefMedlineGoogle Scholar
  • 215. Lincoff A.M., Bittl J.A., Harrington R.A.et al. : "Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial". JAMA 2003; 289: 853.

    CrossrefMedlineGoogle Scholar
  • 216. Kastrati A., Neumann F.J., Mehilli J.et al. : "Bivalirudin versus unfractionated heparin during percutaneous coronary intervention". N Engl J Med 2008; 359: 688.

    CrossrefMedlineGoogle Scholar
  • 217. Stone G.W., Witzenbichler B., Guagliumi G.et al. : "Bivalirudin during primary PCI in acute myocardial infarction". N Engl J Med 2008; 358: 2218.

    CrossrefMedlineGoogle Scholar
  • 218. Cohen M., Levine G.N., Pieper K.S.et al. : "Enoxaparin 0.3 mg/kg IV supplement for patients transitioning to PCI after subcutaneous enoxaparin therapy for NSTE ACS: a subgroup analysis from the SYNERGY trial". Catheter Cardiovasc Interv 2010; 75: 928.

    MedlineGoogle Scholar
  • 219. Collet J.P., Montalescot G., Lison L.et al. : "Percutaneous coronary intervention after subcutaneous enoxaparin pretreatment in patients with unstable angina pectoris". Circulation 2001; 103: 658.

    CrossrefMedlineGoogle Scholar
  • 220. Collet J.P., Montalescot G., Golmard J.L.et al. : "Subcutaneous enoxaparin with early invasive strategy in patients with acute coronary syndromes". Am Heart J 2004; 147: 655.

    CrossrefMedlineGoogle Scholar
  • 221. Martin J.L., Fry E.T., Sanderink G.J.et al. : "Reliable anticoagulation with enoxaparin in patients undergoing percutaneous coronary intervention: the pharmacokinetics of enoxaparin in PCI (PEPCI) study". Catheter Cardiovasc Interv 2004; 61: 163.

    CrossrefMedlineGoogle Scholar
  • 222. Levine G.N. and Ferrando T. : "Degree of anticoagulation after one subcutaneous and one subsequent intravenous booster dose of enoxaparin: implications for patients with acute coronary syndromes undergoing early percutaneous coronary intervention". J Thromb Thrombolysis 2004; 17: 167.

    CrossrefMedlineGoogle Scholar
  • 223. Steg P.G., Mehta S., Jolly S.et al. : "Fondaparinux with UnfracTionated heparin dUring Revascularization in Acute coronary syndromes (FUTURA/OASIS 8): a randomized trial of intravenous unfractionated heparin during percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux". Am Heart J 2010; 160: 1029.

    CrossrefMedlineGoogle Scholar
  • 224. Montalescot G., Gallo R., White H.D.et al. : "Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention 1-year results from the STEEPLE (SafeTy and efficacy of enoxaparin in percutaneous coronary intervention patients, an international randomized evaluation) trial". JACC Cardiovasc Interv 2009; 2: 1083.

    View ArticleGoogle Scholar
  • 225. Choussat R., Montalescot G., Collet J.P.et al. : "A unique, low dose of intravenous enoxaparin in elective percutaneous coronary intervention". J Am Coll Cardiol 2002; 40: 1943.

    View ArticleGoogle Scholar
  • 226. Bybee K.A., Powell B.D., Valeti U.et al. : "Preoperative aspirin therapy is associated with improved postoperative outcomes in patients undergoing coronary artery bypass grafting". Circulation 2005; 112: I286.

    MedlineGoogle Scholar
  • 227. Dacey L.J., Munoz J.J., Johnson E.R.et al. : "Effect of preoperative aspirin use on mortality in coronary artery bypass grafting patients". Ann Thorac Surg 2000; 70: 1986.

    CrossrefMedlineGoogle Scholar
  • 228. Mangano D.T. : "Aspirin and mortality from coronary bypass surgery". N Engl J Med 2002; 347: 1309.

    CrossrefMedlineGoogle Scholar
  • 229. Berger J.S., Frye C.B., Harshaw Q.et al. : "Impact of clopidogrel in patients with acute coronary syndromes requiring coronary artery bypass surgery: a multicenter analysis". J Am Coll Cardiol 2008; 52: 1693.

    View ArticleGoogle Scholar
  • 230. Held C., Asenblad N., Bassand J.P.et al. : "Ticagrelor versus clopidogrel in patients with acute coronary syndromes undergoing coronary artery bypass surgery: results from the PLATO (Platelet Inhibition and Patient Outcomes) trial". J Am Coll Cardiol 2011; 57: 672.

    View ArticleGoogle Scholar
  • 231. Hongo R.H., Ley J., Dick S.E.et al. : "The effect of clopidogrel in combination with aspirin when given before coronary artery bypass grafting". J Am Coll Cardiol 2002; 40: 231.

    View ArticleGoogle Scholar
  • 232. Prasugrel [label] . Indianapolis, IN: Eli Lilly and Co2009.

    Google Scholar
  • 233. Firanescu C.E., Martens E.J., Schonberger J.P.et al. : "Postoperative blood loss in patients undergoing coronary artery bypass surgery after preoperative treatment with clopidogrel. A prospective randomised controlled study". Eur J Cardiothorac Surg 2009; 36: 856.

    MedlineGoogle Scholar
  • 234. Herman C.R., Buth K.J., Kent B.A.et al. : "Clopidogrel increases blood transfusion and hemorrhagic complications in patients undergoing cardiac surgery". Ann Thorac Surg 2010; 89: 397.

    CrossrefMedlineGoogle Scholar
  • 235. Mehta R.H., Sheng S., O'Brien S.M.et al. : "Reoperation for bleeding in patients undergoing coronary artery bypass surgery: incidence, risk factors, time trends, and outcomes". Circ Cardiovasc Qual Outcomes 2009; 2: 583.

    CrossrefMedlineGoogle Scholar
  • 236. Bizzarri F., Scolletta S., Tucci E.et al. : "Perioperative use of tirofiban hydrochloride (Aggrastat) does not increase surgical bleeding after emergency or urgent coronary artery bypass grafting". J Thorac Cardiovasc Surg 2001; 122: 1181.

    CrossrefMedlineGoogle Scholar
  • 237. Dyke C.M., Bhatia D., Lorenz T.J.et al. : "Immediate coronary artery bypass surgery after platelet inhibition with eptifibatide: results from PURSUIT. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrelin Therapy". Ann Thorac Surg 2000; 70: 866.

    CrossrefMedlineGoogle Scholar
  • 238. Lincoff A.M., LeNarz L.A., Despotis G.J.et al. : "Abciximab and bleeding during coronary surgery: results from the EPILOG and EPISTENT trials. Improve Long-term Outcome with abciximab GP IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibition in STENTing". Ann Thorac Surg 2000; 70: 516.

    CrossrefMedlineGoogle Scholar
  • 239. Mukherjee D., Fang J., Chetcuti S.et al. : "Impact of combination evidence-based medical therapy on mortality in patients with acute coronary syndromes". Circulation 2004; 109: 745.

    CrossrefMedlineGoogle Scholar
  • 240. Gluckman T.J., Sachdev M., Schulman S.P.et al. : "A simplified approach to the management of non-ST-segment elevation acute coronary syndromes". JAMA 2005; 293: 349.

    MedlineGoogle Scholar
  • 241. Dracup K., Alonzo A.A., Atkins J.M.et al. : "The physician's role in minimizing prehospital delay in patients at high risk for acute myocardial infarction: recommendations from the National Heart Attack Alert Program. Working Group on Educational Strategies To Prevent Prehospital Delay in Patients at High Risk for Acute Myocardial Infarction". Ann Intern Med 1997; 126: 645.

    CrossrefMedlineGoogle Scholar
  • 242. Abraham N.S., Hlatky M.A., Antman E.M.et al. : "ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. A report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents". J Am Coll Cardiol 2010; 56: 2051.

    View ArticleGoogle Scholar
  • 243. Bhatt D.L., Cryer B.L., Contant C.F.et al. : "Clopidogrel with or without omeprazole in coronary artery disease". N Engl J Med 2010; 363: 1909.

    CrossrefMedlineGoogle Scholar
  • 244. Wenger N.K., Froelicher E.S., Smith L.K.et al. : "Cardiac rehabilitation as secondary prevention. Agency for Health Care Policy and Research and National Heart, Lung, and Blood Institute". Clin Pract Guidel Quick Ref Guide Clin 1995; : 1.

    MedlineGoogle Scholar
  • 245. Fletcher G.F., Ades P.A., Kligfield P.et al. : "Exercise standards for testing and training: a scientific statement from the American Heart Association". Circulation 2013; 128: 873.

    CrossrefMedlineGoogle Scholar
  • 246. Balady G.J., Williams M.A., Ades P.A.et al. : "Core components of cardiac rehabilitation/secondary prevention programs: 2007 update: a scientific statement from the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical Cardiology; the Councils on Cardiovascular Nursing, Epidemiology and Prevention, and Nutrition, Physical Activity, and Metabolism; and the American Association of Cardiovascular and Pulmonary Rehabilitation". Circulation 2007; 115: 2675.

    CrossrefMedlineGoogle Scholar
  • 247. Taylor R.S., Brown A., Ebrahim S.et al. : "Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials". Am J Med 2004; 116: 682.

    CrossrefMedlineGoogle Scholar
  • 248. "Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23)". MMWR Morb Mortal Wkly Rep 2010; 59: 1102.

    Google Scholar
  • 249. "Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR Morb Mortal Wkly Rep 2012; 61: 816.

    MedlineGoogle Scholar
  • 250. "Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR Recomm Rep 1997; 46: 1.

    Google Scholar
  • 251. Flaker G.C., Warnica J.W., Sacks F.M.et al. : "Pravastatin prevents clinical events in revascularized patients with average cholesterol concentrations. Cholesterol and Recurrent Events CARE Investigators". J Am Coll Cardiol 1999; 34: 106.

    View ArticleGoogle Scholar
  • 252. Antman E.M., Bennett J.S., Daugherty A.et al. : "Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association". Circulation 2007; 115: 1634.

    CrossrefMedlineGoogle Scholar
  • 253. McGettigan P. and Henry D. : "Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2". JAMA 2006; 296: 1633.

    CrossrefMedlineGoogle Scholar
  • 254. Bjelakovic G., Nikolova D., Gluud L.L.et al. : "Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis". JAMA 2007; 297: 842.

    CrossrefMedlineGoogle Scholar
  • 255. Mosca L., Banka C.L., Benjamin E.J.et al. : "Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update". J Am Coll Cardiol 2007; 49: 1230.

    View ArticleGoogle Scholar
  • 256. Lonn E., Yusuf S., Arnold M.J.et al. : "Homocysteine lowering with folic acid and B vitamins in vascular disease". N Engl J Med 2006; 354: 1567.

    CrossrefMedlineGoogle Scholar
  • 257. Bonaa K.H., Njolstad I., Ueland P.M.et al. : "Homocysteine lowering and cardiovascular events after acute myocardial infarction". N Engl J Med 2006; 354: 1578.

    CrossrefMedlineGoogle Scholar
  • 258. Manson J.E., Hsia J., Johnson K.C.et al. : "Estrogen plus progestin and the risk of coronary heart disease". N Engl J Med 2003; 349: 523.

    CrossrefMedlineGoogle Scholar
  • 259. Wassertheil-Smoller S., Psaty B., Greenland P.et al. : "Association between cardiovascular outcomes and antihypertensive drug treatment in older women". JAMA 2004; 292: 2849.

    CrossrefMedlineGoogle Scholar
  • 260. Rossouw J.E., Anderson G.L., Prentice R.L.et al. : "Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial". JAMA 2002; 288: 321.

    CrossrefMedlineGoogle Scholar
  • 261. Naylor M., Brooten D., Jones R.et al. : "Comprehensive discharge planning for the hospitalized elderly. A randomized clinical trial". Ann Intern Med 1994; 120: 999.

    CrossrefMedlineGoogle Scholar
  • 262. Coleman E.A., Parry C., Chalmers S.et al. : "The care transitions intervention: results of a randomized controlled trial". Arch Intern Med 2006; 166: 1822.

    CrossrefMedlineGoogle Scholar
  • 263. Young W., Rewa G., Goodman S.G.et al. : "Evaluation of a community-based inner-city disease management program for postmyocardial infarction patients: a randomized controlled trial". CMAJ 2003; 169: 905.

    MedlineGoogle Scholar
  • 264. Jack B.W., Chetty V.K., Anthony D.et al. : "A reengineered hospital discharge program to decrease rehospitalization: a randomized trial". Ann Intern Med 2009; 150: 178.

    CrossrefMedlineGoogle Scholar
  • 265. Lappe J.M., Muhlestein J.B., Lappe D.L.et al. : "Improvements in 1-year cardiovascular clinical outcomes associated with a hospital-based discharge medication program". Ann Intern Med 2004; 141: 446.

    CrossrefMedlineGoogle Scholar
  • 266. Leon A.S., Franklin B.A., Costa F.et al. : "Cardiac rehabilitation and secondary prevention of coronary heart disease: an American Heart Association scientific statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity), in collaboration with the American Association of Cardiovascular and Pulmonary Rehabilitation". Circulation 2005; 111: 369.

    CrossrefMedlineGoogle Scholar
  • 267. Suaya J.A., Stason W.B., Ades P.A.et al. : "Cardiac rehabilitation and survival in older coronary patients". J Am Coll Cardiol 2009; 54: 25.

    View ArticleGoogle Scholar
  • 268. MMWR Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP) - United States, 2012-2013 Influenza Season. Centers for Disease Control and Prevention. 2012.

    Google Scholar
  • 269. Alexander K.P., Newby L.K., Cannon C.P.et al. : "Acute coronary care in the elderly, part I: non-ST-segment-elevation acute coronary syndromes: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology". Circulation 2007; 115: 2549.

    CrossrefMedlineGoogle Scholar
  • 270. Gale C.P., Cattle B.A., Woolston A.et al. : "Resolving inequalities in care? Reduced mortality in the elderly after acute coronary syndromes. The Myocardial Ischaemia National Audit Project 2003-2010". Eur Heart J 2012; 33: 630.

    CrossrefMedlineGoogle Scholar
  • 271. Devlin G., Gore J.M., Elliott J.et al. : "Management and 6-month outcomes in elderly and very elderly patients with high-risk non-ST-elevation acute coronary syndromes: The Global Registry of Acute Coronary Events". Eur Heart J 2008; 29: 1275.

    CrossrefMedlineGoogle Scholar
  • 272. Damman P., Clayton T., Wallentin L.et al. : "Effects of age on long-term outcomes after a routine invasive or selective invasive strategy in patients presenting with non-ST segment elevation acute coronary syndromes: a collaborative analysis of individual data from the FRISC II - IC". Heart 2012; 98: 207.

    CrossrefMedlineGoogle Scholar
  • 273. Bach R.G., Cannon C.P., Weintraub W.S.et al. : "The effect of routine, early invasive management on outcome for elderly patients with non-ST-segment elevation acute coronary syndromes". Ann Intern Med 2004; 141: 186.

    CrossrefMedlineGoogle Scholar
  • 274. Corsonello A., Pedone C. and Incalzi R.A. : "Age-related pharmacokinetic and pharmacodynamic changes and related risk of adverse drug reactions". Curr Med Chem 2010; 17: 571.

    MedlineGoogle Scholar
  • 275. Trifiro G. and Spina E. : "Age-related changes in pharmacodynamics: focus on drugs acting on central nervous and cardiovascular systems". Curr Drug Metab 2011; 12: 611.

    Google Scholar
  • 276. Alexander K.P., Chen A.Y., Roe M.T.et al. : "Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes". JAMA 2005; 294: 3108.

    CrossrefMedlineGoogle Scholar
  • 277. Yourman L.C., Lee S.J., Schonberg M.A.et al. : "Prognostic indices for older adults: a systematic review". JAMA 2012; 307: 182.

    CrossrefMedlineGoogle Scholar
  • 278. Fenning S., Woolcock R., Haga K.et al. : "Identifying acute coronary syndrome patients approaching end-of-life". PLoS One 2012; 7: e35536.

    MedlineGoogle Scholar
  • 279. Tinetti M.E., Bogardus S.T. and Agostini J.V. : "Potential pitfalls of disease-specific guidelines for patients with multiple conditions". N Engl J Med 2004; 351: 2870.

    CrossrefMedlineGoogle Scholar
  • 280. Lopes R.D., Alexander K.P., Manoukian S.V.et al. : "Advanced age, antithrombotic strategy, and bleeding in non-ST-segment elevation acute coronary syndromes: results from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial". J Am Coll Cardiol 2009; 53: 1021.

    View ArticleGoogle Scholar
  • 281. Lemesle G., Labriolle De, Bonello L.et al. : "Impact of bivalirudin on in-hospital bleeding and six-month outcomes in octogenarians undergoing percutaneous coronary intervention". Catheter Cardiovasc Interv 2009; 74: 428.

    CrossrefGoogle Scholar
  • 282. Summaria F., Romagnoli E., De Luca L.et al. : "Feasibility and safety of transradial approach and bivalirudin treatment in elderly patients undergoing early invasive strategy for ACS: 'The OLDER Research Project' preliminary study". J Cardiovasc Med (Hagerstown ) 2012; 13: 351.

    CrossrefGoogle Scholar
  • 283. McKellar S.H., Brown M.L., Frye R.L.et al. : "Comparison of coronary revascularization procedures in octogenarians: a systematic review and meta-analysis". Nat Clin Pract Cardiovasc Med 2008; 5: 738.

    CrossrefMedlineGoogle Scholar
  • 284. Kimura T., Morimoto T., Furukawa Y.et al. : "Long-term outcomes of coronary-artery bypass graft surgery versus percutaneous coronary intervention for multivessel coronary artery disease in the bare-metal stent era". Circulation 2008; 118: S199.

    CrossrefMedlineGoogle Scholar
  • 285. Dacey L.J., Likosky D.S., Ryan T.J.et al. : "Long-term survival after surgery versus percutaneous intervention in octogenarians with multivessel coronary disease". Ann Thorac Surg 2007; 84: 1904.

    CrossrefMedlineGoogle Scholar
  • 286. Ramanathan K.B., Weiman D.S., Sacks J.et al. : "Percutaneous intervention versus coronary bypass surgery for patients older than 70 years of age with high-risk unstable angina". Ann Thorac Surg 2005; 80: 1340.

    CrossrefMedlineGoogle Scholar
  • 287. Sheridan B.C., Stearns S.C., Rossi J.S.et al. : "Three-year outcomes of multivessel revascularization in very elderly acute coronary syndrome patients". Ann Thorac Surg 2010; 89: 1889.

    CrossrefMedlineGoogle Scholar
  • 288. Nissinen J., Wistbacka J.O., Loponen P.et al. : "Coronary artery bypass surgery in octogenarians: long-term outcome can be better than expected". Ann Thorac Surg 2010; 89: 1119.

    Google Scholar
  • 289. Spacek R., Widimsky P., Straka Z.et al. : "Value of first day angiography/angioplasty in evolving Non-ST segment elevation myocardial infarction: an open multicenter randomized trial. The VINO Study". Eur Heart J 2002; 23: 230.

    CrossrefMedlineGoogle Scholar
  • 290. Mehta S.R., Cannon C.P., Fox K.A.et al. : "Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials". JAMA 2005; 293: 2908.

    CrossrefMedlineGoogle Scholar
  • 291. Hochman J.S., Sleeper L.A., Webb J.G.et al. : "Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock". N Engl J Med 1999; 341: 625.

    CrossrefMedlineGoogle Scholar
  • 292. Bhatt D.L., Roe M.T., Peterson E.D.et al. : "Utilization of early invasive management strategies for high-risk patients with non-ST-segment elevation acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative". JAMA 2004; 292: 2096.

    CrossrefMedlineGoogle Scholar
  • 293. Hochman J.S., Sleeper L.A., Webb J.G.et al. : "Early revascularization and long-term survival in cardiogenic shock complicating acute myocardial infarction". JAMA 2006; 295: 2511.

    CrossrefMedlineGoogle Scholar
  • 294. Jeger R.V., Urban P., Harkness S.M.et al. : "Early revascularization is beneficial across all ages and a wide spectrum of cardiogenic shock severity: a pooled analysis of trials". Acute Card Care 2011; 13: 14.

    CrossrefMedlineGoogle Scholar
  • 295. Norhammar A., Malmberg K., Diderholm E.et al. : "Diabetes mellitus: the major risk factor in unstable coronary artery disease even after consideration of the extent of coronary artery disease and benefits of revascularization". J Am Coll Cardiol 2004; 43: 585.

    View ArticleGoogle Scholar
  • 296. Fox K.A., Clayton T.C., Damman P.et al. : "Long-term outcome of a routine versus selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome a meta-analysis of individual patient data". J Am Coll Cardiol 2010; 55: 2435.

    View ArticleGoogle Scholar
  • 297. Fox K.A., Poole-Wilson P., Clayton T.C.et al. : "5-year outcome of an interventional strategy in non-ST-elevation acute coronary syndrome: the British Heart Foundation RITA 3 randomised trial". Lancet 2005; 366: 914.

    CrossrefMedlineGoogle Scholar
  • 298. Adesanya A.O., de Lemos J.A., Greilich N.B.et al. : "Management of perioperative myocardial infarction in noncardiac surgical patients". Chest 2006; 130: 584.

    CrossrefMedlineGoogle Scholar
  • 299. Berger P.B., Bellot V., Bell M.R.et al. : "An immediate invasive strategy for the treatment of acute myocardial infarction early after noncardiac surgery". Am J Cardiol 2001; 87: 1100. A6, A9.

    CrossrefMedlineGoogle Scholar
  • 300. Bertrand M.E., Lablanche J.M., Tilmant P.Y.et al. : "Frequency of provoked coronary arterial spasm in 1089 consecutive patients undergoing coronary arteriography". Circulation 1982; 65: 1299.

    CrossrefMedlineGoogle Scholar
  • 301. Suwaidi J.A., Hamasaki S., Higano S.T.et al. : "Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction". Circulation 2000; 101: 948.

    CrossrefMedlineGoogle Scholar
  • 302. Bugiardini R., Manfrini O., Pizzi C.et al. : "Endothelial function predicts future development of coronary artery disease: a study of women with chest pain and normal coronary angiograms". Circulation 2004; 109: 2518.

    CrossrefMedlineGoogle Scholar
  • 303. Gualandro D.M., Calderaro D., Yu P.C.et al. : "Acute myocardial infarction after noncardiac surgery". Arq Bras Cardiol 2012; 99: 1060.

    MedlineGoogle Scholar
  • 304. Gualandro D.M., Yu P.C., Calderaro D.et al. : "II Guidelines for perioperative evaluation of the Brazilian Society of Cardiology". Arq Bras Cardiol 2011; 96: 1.

    Google Scholar
  • 305. Villacorta J.H., Castro I.S., Godinho M.et al. : "B-type natriuretic peptide is predictive of postoperative events in orthopedic surgery". Arq Bras Cardiol 2010; 95: 743.

    MedlineGoogle Scholar
  • 306. "[Guidelines for unstable angina and non-ST-segment elevation myocardial infarction of the Brazilian Society of Cardiology (II Edition, 2007)]". Arq Bras Cardiol 2007; 89: e89.

    MedlineGoogle Scholar
  • 307. Wright R.S., Reeder G.S., Herzog C.A.et al. : "Acute myocardial infarction and renal dysfunction: a high-risk combination". Ann Intern Med 2002; 137: 563.

    CrossrefMedlineGoogle Scholar
  • 308. Shlipak M.G., Heidenreich P.A., Noguchi H.et al. : "Association of renal insufficiency with treatment and outcomes after myocardial infarction in elderly patients". Ann Intern Med 2002; 137: 555.

    CrossrefMedlineGoogle Scholar
  • 309. Charytan D.M., Wallentin L., Lagerqvist B.et al. : "Early angiography in patients with chronic kidney disease: a collaborative systematic review". Clin J Am Soc Nephrol 2009; 4: 1032.

    CrossrefMedlineGoogle Scholar
  • 310. Szummer K., Lundman P., Jacobson S.H.et al. : "Influence of renal function on the effects of early revascularization in non-ST-elevation myocardial infarction: data from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART)". Circulation 2009; 120: 851.

    CrossrefMedlineGoogle Scholar
  • 311. Hutchinson-Jaffe A.B., Goodman S.G., Yan R.T.et al. : "Comparison of baseline characteristics, management and outcome of patients with non-ST-segment elevation acute coronary syndrome in versus not in clinical trials". Am J Cardiol 2010; 106: 1389.

    CrossrefGoogle Scholar
  • 312. Akhter N., Milford-Beland S., Roe M.T.et al. : "Gender differences among patients with acute coronary syndromes undergoing percutaneous coronary intervention in the American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR)". Am Heart J 2009; 157: 141.

    CrossrefMedlineGoogle Scholar
  • 313. Blomkalns A.L., Chen A.Y., Hochman J.S.et al. : "Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative". J Am Coll Cardiol 2005; 45: 832.

    View ArticleGoogle Scholar
  • 314. Lansky A.J., Mehran R., Cristea E.et al. : "Impact of gender and antithrombin strategy on early and late clinical outcomes in patients with non-ST-elevation acute coronary syndromes (from the ACUITY trial)". Am J Cardiol 2009; 103: 1196.

    CrossrefMedlineGoogle Scholar
  • 315. Alexander K.P., Chen A.Y., Newby L.K.et al. : "Sex differences in major bleeding with glycoprotein IIb/IIIa inhibitors: results from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) initiative". Circulation 2006; 114: 1380.

    CrossrefMedlineGoogle Scholar
  • 316. Dolor R.J., Melloni C., Chatterjee R.et al. : Treatment strategies for women with coronary artery disease. Comparative effectiveness review no. 66 . Rockville, MD: Agency for healthcare Research and Quality2012. AHRQ publication no. 12-EHC070-EF. Available at: http://www.effectivehealthcare.ahrq.gov/reports/final.cfm. Accessed July 30, 2014.

    Google Scholar
  • 317. Glaser R., Herrmann H.C., Murphy S.A.et al. : "Benefit of an early invasive management strategy in women with acute coronary syndromes". JAMA 2002; 288: 3124.

    CrossrefMedlineGoogle Scholar
  • 318. Regitz-Zagrosek V., Blomstrom L.C., Borghi C.et al. : "ESC guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC)". Eur Heart J 2011; 32: 3147.

    CrossrefMedlineGoogle Scholar
  • 319. Melloni C., Alexander K.P., Chen A.Y.et al. : "Unfractionated heparin dosing and risk of major bleeding in non-ST-segment elevation acute coronary syndromes". Am Heart J 2008; 156: 209.

    CrossrefMedlineGoogle Scholar
  • 320. LaPointe N.M., Chen A.Y., Alexander K.P.et al. : "Enoxaparin dosing and associated risk of in-hospital bleeding and death in patients with non ST-segment elevation acute coronary syndromes". Arch Intern Med 2007; 167: 1539.

    CrossrefMedlineGoogle Scholar
  • 321. Carson J.L., Carless P.A. and Hebert P.C. : "Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion". Cochrane Database Syst Rev 2012; 4: CD002042.

    Google Scholar
  • 322. Carson J.L., Grossman B.J., Kleinman S.et al. : "Red blood cell transfusion: a clinical practice guideline from the AABB". Ann Intern Med 2012; 157: 49.

    CrossrefMedlineGoogle Scholar
  • 323. Rao S.V., Jollis J.G., Harrington R.A.et al. : "Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes". JAMA 2004; 292: 1555.

    CrossrefMedlineGoogle Scholar
  • 324. Alexander K.P., Chen A.Y., Wang T.Y.et al. : "Transfusion practice and outcomes in non-ST-segment elevation acute coronary syndromes". Am Heart J 2008; 155: 1047.

    CrossrefMedlineGoogle Scholar
  • 325. Yang X., Alexander K.P., Chen A.Y.et al. : "The implications of blood transfusions for patients with non-ST-segment elevation acute coronary syndromes: results from the CRUSADE National Quality Improvement Initiative". J Am Coll Cardiol 2005; 46: 1490.

    View ArticleGoogle Scholar
  • 326. Baumann B.M., Perrone J., Hornig S.E.et al. : "Randomized, double-blind, placebo-controlled trial of diazepam, nitroglycerin, or both for treatment of patients with potential cocaine-associated acute coronary syndromes". Acad Emerg Med 2000; 7: 878.

    CrossrefMedlineGoogle Scholar
  • 327. Honderick T., Williams D., Seaberg D.et al. : "A prospective, randomized, controlled trial of benzodiazepines and nitroglycerine or nitroglycerine alone in the treatment of cocaine-associated acute coronary syndromes". Am J Emerg Med 2003; 21: 39.

    MedlineGoogle Scholar
  • 328. Hollander J.E. : "Cocaine intoxication and hypertension". Ann Emerg Med 2008; 51: S18.

    MedlineGoogle Scholar
  • 329. Schwartz B.G., Rezkalla S. and Kloner R.A. : "Cardiovascular effects of cocaine". Circulation 2010; 122: 2558.

    CrossrefMedlineGoogle Scholar
  • 330. Parodi O., Maseri A. and Simonetti I. : "Management of unstable angina at rest by verapamil. A double-blind cross-over study in coronary care unit". Br Heart J 1979; 41: 167.

    CrossrefMedlineGoogle Scholar
  • 331. Chahine R.A., Feldman R.L., Giles T.D.et al. : "Randomized placebo-controlled trial of amlodipine in vasospastic angina. Amlodipine Study 160 Group". J Am Coll Cardiol 1993; 21: 1365.

    View ArticleGoogle Scholar
  • 332. Lombardi M., Morales M.A., Michelassi C.et al. : "Efficacy of isosorbide-5-mononitrate versus nifedipine in preventing spontaneous and ergonovine-induced myocardial ischaemia. A double-blind, placebo-controlled study". Eur Heart J 1993; 14: 845.

    CrossrefMedlineGoogle Scholar
  • 333. Fukumoto Y., Yasuda S., Ito A.et al. : "Prognostic effects of benidipine in patients with vasospastic angina: comparison with diltiazem and amlodipine". J Cardiovasc Pharmacol 2008; 51: 253.

    CrossrefGoogle Scholar
  • 334. Kimura E. and Kishida H. : "Treatment of variant angina with drugs: a survey of 11 cardiology institutes in Japan". Circulation 1981; 63: 844.

    CrossrefMedlineGoogle Scholar
  • 335. Kugiyama K., Ohgushi M., Sugiyama S.et al. : "Supersensitive dilator response to nitroglycerin but not to atrial natriuretic peptide in spastic coronary arteries in coronary spastic angina". Am J Cardiol 1997; 79: 606.

    Google Scholar
  • 336. Tani S., Nagao K., Anazawa T.et al. : "Treatment of coronary spastic angina with a statin in addition to a calcium channel blocker: a pilot study". J Cardiovasc Pharmacol 2008; 52: 28.

    CrossrefMedlineGoogle Scholar
  • 337. Yasue H., Mizuno Y., Harada E.et al. : "Effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on coronary spasm after withdrawal of calcium-channel blockers". J Am Coll Cardiol 2008; 51: 1742.

    View ArticleGoogle Scholar
  • 338. Sugiishi M. and Takatsu F. : "Cigarette smoking is a major risk factor for coronary spasm". Circulation 1993; 87: 76.

    CrossrefMedlineGoogle Scholar
  • 339. Nobuyoshi M., Abe M., Nosaka H.et al. : "Statistical analysis of clinical risk factors for coronary artery spasm: identification of the most important determinant". Am Heart J 1992; 124: 32.

    CrossrefMedlineGoogle Scholar
  • 340. Yamagishi M., Ito K., Tsutsui H.et al. : "Lesion severity and hypercholesterolemia determine long-term prognosis of vasospastic angina treated with calcium channel antagonists". Circ J 2003; 67: 1029.

    CrossrefMedlineGoogle Scholar
  • 341. Koizumi T., Yokoyama M., Namikawa S.et al. : "Location of focal vasospasm provoked by ergonovine maleate within coronary arteries in patients with vasospastic angina pectoris". Am J Cardiol 2006; 97: 1322.

    CrossrefMedlineGoogle Scholar
  • 342. Ong P., Athanasiadis A., Hill S.et al. : "Coronary artery spasm as a frequent cause of acute coronary syndrome: The CASPAR (Coronary Artery Spasm in Patients With Acute Coronary Syndrome) Study". J Am Coll Cardiol 2008; 52: 523.

    View ArticleGoogle Scholar
  • 343. Cheng C.W., Yang N.I., Lin K.J.et al. : "Role of coronary spasm for a positive noninvasive stress test result in angina pectoris patients without hemodynamically significant coronary artery disease". Am J Med Sci 2008; 335: 354.

    CrossrefGoogle Scholar
  • 344. Wakabayashi K., Suzuki H., Honda Y.et al. : "Provoked coronary spasm predicts adverse outcome in patients with acute myocardial infarction: a novel predictor of prognosis after acute myocardial infarction". J Am Coll Cardiol 2008; 52: 518.

    View ArticleGoogle Scholar
  • 345. Herrmann J., Kaski J. and Lerman A. : "Coronary microvascular dysfunction in the clinical setting: from mystery to reality". Eur Heart J 2012; 33: 2771.

    CrossrefMedlineGoogle Scholar
  • 346. Cannon R.O.I. and Epstein S.E. : "‘Microvascular angina’ as a cause of chest pain with angiographically normal coronary arteries". Am J Cardiol 1988; 61: 1338.

    CrossrefMedlineGoogle Scholar
  • 347. Johnson B.D., Shaw L.J., Buchthal S.D.et al. : "Prognosis in women with myocardial ischemia in the absence of obstructive coronary disease: results from the National Institutes of Health-National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE)". Circulation 2004; 109: 2993.

    CrossrefMedlineGoogle Scholar
  • 348. Doyle M., Weinberg N., Pohost G.M.et al. : "Prognostic value of global MR myocardial perfusion imaging in women with suspected myocardial ischemia and no obstructive coronary disease: results from the NHLBI-sponsored WISE (Women's Ischemia Syndrome Evaluation) study". JACC Cardiovasc Imaging 2010; 3: 1030.

    View ArticleGoogle Scholar
  • 349. Eitel I., von Knobelsdorff-Brenkenhoff F., Bernhardt P.et al. : "Clinical characteristics and cardiovascular magnetic resonance findings in stress (takotsubo) cardiomyopathy". JAMA 2011; 306: 277.

    MedlineGoogle Scholar
  • 350. Bybee K.A. and Prasad A. : "Stress-related cardiomyopathy syndromes". Circulation 2008; 118: 397.

    CrossrefMedlineGoogle Scholar
  • 351. Eitel I., Behrendt F., Schindler K.et al. : "Differential diagnosis of suspected apical ballooning syndrome using contrast-enhanced magnetic resonance imaging". Eur Heart J 2008; 29: 2651.

    CrossrefMedlineGoogle Scholar
  • 352. Sharkey S.W., Windenburg D.C., Lesser J.R.et al. : "Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy". J Am Coll Cardiol 2010; 55: 333.

    View ArticleGoogle Scholar
  • 353. American Heart Association. Get With the Guidelines. Available at: http://www.heart.org/HEARTORG/HealthcareResearch/GetWithTheGuidelinesHFStroke/Get-With-The-Guidelines—HFStroke_UCM_001099_SubHomePage.jsp. Accessed August 28, 2014.

    Google Scholar
  • 354. ASSENT-4 PCI Investigators : "Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial". Lancet 2006; 367: 569.

    CrossrefMedlineGoogle Scholar
  • 355. Bonow R.O., Masoudi F.A., Rumsfeld J.S.et al. : "ACC/AHA classification of care metrics: performance measures and quality metrics: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures". J Am Coll Cardiol 2008; 52: 2113.

    View ArticleGoogle Scholar
  • 356. Henry T.D., Sharkey S.W., Burke M.N.et al. : "A regional system to provide timely access to percutaneous coronary intervention for ST-elevation myocardial infarction". Circulation 2007; 116: 721.

    CrossrefMedlineGoogle Scholar
  • 357. Krumholz H.M., Anderson J.L., Bachelder B.L.et al. : "ACC/AHA 2008 performance measures for adults with ST-elevation and non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures (Writing Committee to Develop Performance Measures for ST-Elevation and Non-ST-Elevation Myocardial Infarction)". J Am Coll Cardiol 2008; 52: 2046.

    View ArticleGoogle Scholar
  • 358. Le May M.R., So D.Y., Dionne R.et al. : "A citywide protocol for primary PCI in ST-segment elevation myocardial infarction". N Engl J Med 2008; 358: 231.

    CrossrefMedlineGoogle Scholar
  • 359. National Cardiovascular Data Registry. Action Registry–GWTG. 2009. Available at: http://www.ncdr.com/webncdr/ACTION/Default.aspx. Accessed June 10, 2009.

    Google Scholar
  • 360. QualityNet.com. Measure Comparison (Inpatient Hospital Quality Measures). 2009. Available at: http://www.qualitynet.org/dcs/ContentServer?c=Page&pagename=QnetPublic%2FPage%2FQnetTier3&cid=1138900297065. Accessed June 10, 2009.

    Google Scholar
  • 361. The Joint Commission. Acute Myocardial Infarction Core Measure Set. 2009. Available at: http://www.jointcommission.org/core_measure_sets.aspx. Accessed August 28, 2014.

    Google Scholar
  • 362. Anderson J.L., Adams C.D., Antman E.M.et al. : "ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction)". J Am Coll Cardiol 2007; 50: e1.

    View ArticleGoogle Scholar
  • 363. Mehta S.R., Tanguay J.F., Eikelboom J.W.et al. : "Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial". Lancet 2010; 376: 1233.

    CrossrefMedlineGoogle Scholar

Footnotes

Developed in Collaboration With the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons

Endorsed by the American Association for Clinical Chemistry

The writing committee gratefully acknowledges the memory of Dr. Francis M. Fesmire (representative of the American College of Emergency Physicians), who died during the development of this document but contributed immensely to our understanding of non–ST-elevation acute coronary syndromes.

This document was approved by the American College of Cardiology Board of Trustees and the American Heart Association Science Advisory and Coordinating Committee in August 2014.

The American College of Cardiology requests that this document be cited as follows: Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED, Sabatine MS, Smalling RW, Zieman SJ. 2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;64:2645–87.

This article is copublished in Circulation.

Copies: This document is available on the World Wide Web sites of the American College of Cardiology ( www.cardiosource.org) and the American Heart Association ( my.americanheart.org). For copies of this document, please contact the Elsevier Inc. Reprint Department, fax (212) 633-3820, e-mail [email protected].

Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American College of Cardiology. Requests may be completed online via the Elsevier site ( http://www.elsevier.com/authors/obtainingpermission-to-re-useelsevier-material).

Listen to this manuscript's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.

You can also listen to this issue's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.