Pharmacodynamic Effects of Vorapaxar in Patients With and Without Diabetes Mellitus Treated With Dual Antiplatelet Therapy: Results of the OPTIMUS -5 (Optimizing Anti-Platelet Therapy in Diabetes Mellitus -5) Study

•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.