Vorapaxar: a review of its use in the long-term secondary prevention of atherothrombotic events.

Vorapaxar (Zontivity®) is a first-in-class, potent and orally-active protease-activated receptor 1 (PAR-1) antagonist that blocks thrombin-mediated platelet activation without interfering with thrombin-mediated fibrin deposition. The long-term efficacy of once-daily vorapaxar added to standard antiplatelet therapy (aspirin with or without clopidogrel) in the secondary prevention of atherothrombotic events in patients with a history of myocardial infarction (MI), ischaemic stroke or peripheral arterial disease was investigated in the large, multinational TRA 2°P-TIMI 50 trial. Compared with placebo, vorapaxar significantly reduced the risk of the composite endpoints of cardiovascular (CV) death, MI or stroke, and CV death, MI, stroke or urgent coronary revascularization in the overall trial population. Vorapaxar also significantly reduced the risk of these composite endpoints in the subgroup of patients with prior MI (the largest qualifying disease cohort) and the subset of post-MI patients with no history of stroke or transient ischaemic attack (TIA). Vorapaxar significantly increased the risk of GUSTO moderate and/or severe bleeding in the overall trial population and all key subgroups (including post-MI patients with no history of stroke or TIA). Vorapaxar also significantly increased the risk of intracranial haemorrhage (ICH) in the overall trial population and the subgroup of patients with prior stroke, but not the subgroup of post-MI patients or the subset of post-MI patients with no history of stroke or TIA. Based on these results, vorapaxar has been approved in the EU as an adjunctive treatment for the secondary prevention of atherothrombotic events in patients with prior MI who do not have a history of stroke, TIA or ICH.