Vorapaxar expands antiplatelet options. Which patients may benefit from thrombin receptor antagonism?

Vorapaxar is the first substance of a new class of antiplatelet drugs that has been tested in large clinical trials. The protease-activated receptor 1 (PAR-1) antagonist inhibits thrombin-induced platelet activation to prevent atherothrombosis. In the phase 3 trials TRACER (acute coronary syndrome) and TRA 2P-TIMI 50 (stable atherosclerosis) reducing ischemic events with vorapaxar came at the cost of bleeding. TRACER compared vorapaxar to placebo in 12,944 patients who had non-ST-segment elevation acute coronary syndromes on top of contemporary treatment including dual antiplatelet therapy (aspirin and clopidogrel). Vorapaxar reduced ischemic events non-significantly, but increased bleeding significantly, therefore not justifying triple antiplatelet therapy in this setting. Follow-up was stopped early because of bleeding. TRA 2P-TIMI 50 examined 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease. Vorapaxar reduced ischemic events and increased bleeding both significantly. Recruitment of patients with prior stroke was stopped early. Net clinical outcome and subgroup analyses suggested that vorapaxar could be beneficial for patients with prior myocardial infarction - but no history of stroke.