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Pharmacodynamic Effects of Vorapaxar in Patients With and Without Diabetes Mellitus: Results of the OPTIMUS-5 Study

Clinical Research

J Am Coll Cardiol Basic Trans Science, 4 (7) 763–775
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Visual Abstract

Highlights

Vorapaxar reduces thrombotic cardiovascular events in patients with atherosclerotic disease, with enhanced effects in those with DM.

Adjunctive vorapaxar therapy reduces platelet-mediated thrombogenicity without affecting clot kinetics in both patients with and those without DM having prior MI/PAD on dual antiplatelet therapy with aspirin and clopidogrel.

The pharmacodynamic effects of vorapaxar occur via selective blockade of the PAR-1 on the platelet membrane without apparent interplay with other platelet signaling pathways.

Aspirin withdrawal, which leaves patients on a background of clopidogrel and vorapaxar, increases markers specific to COX-1–mediated blockade, leading to an increase in platelet-mediated global thrombogenicity, particularly among patients with DM.

Summary

Vorapaxar reduces thrombotic cardiovascular events at the expense of increased bleeding. However, the differential pharmacodynamic (PD) effects of vorapaxar according to diabetes mellitus (DM) status are unknown. Moreover, although withdrawal of aspirin has emerged as a bleeding reduction strategy, the PD effects of stopping aspirin in patients treated with vorapaxar also are unknown. In this prospective PD investigation, vorapaxar was associated with reduced platelet-mediated thrombogenicity without affecting clot kinetics irrespective of DM status. However, platelet-mediated thrombogenicity increased after aspirin withdrawal, particularly among patients with DM. (Optimizing anti-Platelet Therapy In diabetes MellitUS-5 Study [OPTIMUS-5]; NCT02548650)