Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: A prespecified subgroup analysis of the TRA 2°P-TIMI 50 trial

Background Vorapaxar inhibits platelet activation by antagonising thrombin-mediated activation of the proteaseactivated receptor 1 on human platelets. The effect of adding other antiplatelet drugs to aspirin for long-term secondary prevention of thrombotic events in stable patients with previous myocardial infarction is uncertain. We tested this effect in a subgroup of patients from the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-TIMI 50 trial. Methods In TRA 2°P-TIMI 50 - a randomised, placebo-controlled, parallel trial - we randomly assigned patients with a history of atherothrombosis to receive vorapaxar (2 5 mg daily) or matching placebo in a 1:1 ratio. Patients, and those giving treatment, assessing outcomes, and analysing results were masked to treatment allocation. Patients with a qualifying myocardial infarction within the previous 2 weeks to 12 months were analysed as a pre-defined subgroup. The primary efficacy endpoint was cardiovascular death, myocardial infarction, or stroke, analysed by intention to treat. We analysed events by Kaplan-Meier analysis and compared groups with a Cox proportional hazard model. TRA 2°P-TIMI 50 is registered at ClinicalTrials.gov (NCT00526474). Findings 17 779 of 26 449 patients had a qualifying myocardial infarction and were assigned treatment (8898 to vorapaxar and 8881 to placebo). Median follow-up was 2 5 years (IQR 2 0-2 9). Cardiovascular death, myocardial infarction, or stroke occurred in 610 of 8898 patients in the vorapaxar group and 750 of 8881 in the placebo group ( 3-year Kaplan-Meier estimates 8 1% vs 9 7%, HR 0 80, 95% CI 0 72-0 89; p