Outcomes in Stable Patients With Previous Atherothrombotic Events Receiving Vorapaxar Who Experience a New Acute Coronary Event (from TRA2°P-TIMI 50).

Vorapaxar is a first-in-class protease-activated receptor-1 antagonist indicated for secondary prevention in stable patients with previous myocardial infarction (MI) or peripheral artery disease and no cerebrovascular disease. Vorapaxar is not recommended for initiation in the acute phase of acute coronary syndromes (ACS) because of an unfavorable balance between bleeding and efficacy when started in that setting. The aim of this analysis was to investigate outcomes in patients who experienced a new ACS while receiving vorapaxar for long-term secondary prevention. Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic ischemic Events-Thrombolysis In Myocardial Infarction 50 was a randomized, double-blind, placebo-controlled trial of vorapaxar (n = 26,449). We evaluated bleeding and ischemic events during the acute care of patients with a new ACS during the trial. During a median follow-up of 30 months, 799 patients (8.9%) randomized to vorapaxar and 913 (10.0%) to placebo had a new ACS event (p = 0.003); 87% and 86%, respectively, were on study therapy at the time of the event. In a landmark analysis through 7 days after ACS, the rates of Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe bleeding were 0.8% versus 0.8% (hazard ratio [HR] 0.99, 95% CI 0.33 to 2.94) and GUSTO moderate/severe bleeding were 2.5% versus 1.6% (HR 1.59, 95% CI 0.78 to 3.24) with vorapaxar versus placebo. The effect of vorapaxar on cardiovascular death, MI, or stroke (2.4% vs 4.4%; HR 0.54, 95% CI 0.31 to 0.93; p = 0.027) was consistent with the overall trial result. In conclusion, in patients who experience a new ACS event while receiving vorapaxar for secondary prevention, continuing therapy was associated with favorable efficacy without excess severe bleeding during the period of acute ACS management.