Efficacy and safety of vorapaxar as approved for clinical use in the United States

Background: 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. © 2015 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.