Magnani, GiuliaBonaca, MarcBraunwald, EugeneDalby, Anthony J.Fox, Keith A. A.Murphy, Sabina A.Nicolau, José CarlosOude Ophuis, TonScirica, BenjaminSpinar, JindrichTheroux, PierreMorrow, David2015-05-042015Magnani, G., M. P. Bonaca, E. Braunwald, A. J. Dalby, K. A. A. Fox, S. A. Murphy, J. C. Nicolau, et al. 2015. “Efficacy and Safety of Vorapaxar as Approved for Clinical Use in the United States.” Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 4 (3): e001505. doi:10.1161/JAHA.114.001505. http://dx.doi.org/10.1161/JAHA.114.001505.2047-9980http://nrs.harvard.edu/urn-3:HUL.InstRepos:15035018Background: Vorapaxar is a protease‐activated receptor‐1 antagonist approved by the U.S. Food and Drug Administration (FDA) for the reduction of thrombotic cardiovascular (CV) events in patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), without a previous stroke or transient ischemic attack (TIA). Methods and Results: We examined the efficacy and safety of vorapaxar in the intended use population, considering 20 170 patients randomized in the multinational, double‐blinded, placebo‐controlled TRA 2°P‐TIMI 50 trial. Of these, 16 897 qualified with a history of MI in the prior 2 weeks to 1 year and 3273 with PAD. At baseline 97% of the patients were treated with aspirin, 71% with a thienopyridine, and 93% a statin. At 3 years, the endpoint of CV death, MI, or stroke was significantly reduced with vorapaxar compared with placebo (7.9% versus 9.5%, HR, 0.80; 95% CI 0.73 to 0.89; P<0.001). Vorapaxar also significantly reduced the composite of CV death, MI, stroke, and urgent coronary revascularization (10.1% versus 11.8%, HR, 0.83; 95% CI 0.76 to 0.90; P<0.001), as well as the rate of CV death or MI (P<0.001). The safety endpoint of GUSTO moderate or severe bleeding, was increased in the vorapaxar group (3.7 versus 2.4, HR, 1.55; 95% CI 1.30 to 1.86, P<0.001). Intracranial bleeding (ICH) was 0.6% versus 0.4%, P=0.10 with vorapaxar versus placebo, with fatal bleeding 0.2% versus 0.2%; P=0.70. Conclusions: In patients with prior MI or PAD who have not had a previous stroke or TIA, vorapaxar added to standard therapy is effective for long‐term secondary prevention of thrombotic CV events, while increasing moderate or severe bleeding. Clinical Trial Registration URL: clinicaltrials.gov Unique Identifier: NCT00526474.en-USCoronary Heart Diseaseantiplatelet therapyatherosclerosismyocardial infarctionperipheral arterial diseasesecondary preventionvorapaxarJournal Article2015-05-0410.1161/JAHA.114.001505