• Harvey D White, Zhen Huang, Pierluigi Tricoci, Frans Van de Werf, Lars Wallentin, Yuliya Lokhnygina, David J Moliterno, Philip E Aylward, Kenneth W Mahaffey, and Paul W Armstrong.
• Green Lane Cardiovascular Service, Auckland City Hospital and Auckland University, Auckland, New Zealand (H.D.W.).
• J Am Heart Assoc. 2014 Aug 1;3(4).

BackgroundClinical trials traditionally use time-to-first-event analysis embedded within the composite endpoint of cardiovascular death (CVD), myocardial infarction (MI), or stroke. However, many patients have >1 event, and this approach may not reflect overall experience. We addressed this by analyzing all cardiovascular events in TRACER.Methods And ResultsTRACER randomized 12 944 patients with non-ST-segment elevation acute coronary syndromes to placebo or to protease-activated receptor 1 antagonist vorapaxar with a median follow-up of 502 days (interquartile range, 349 to 667). Analysis of vorapaxar's effect on recurrent CVD, MI, or stroke was prespecified using the Wei, Lin, and Weissfeld approach. Vorapaxar did not reduce the first occurrence of the primary endpoint of CVD, MI, stroke, revascularization, or rehospitalization for recurrent ischemia, but reduced the secondary composite endpoint of CVD, MI, or stroke (14.7% vorapaxar vs. 16.4% placebo; hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.02; number needed to treat [NNT], 81). Recurrent secondary events occurred in 2.7% of patients. Vorapaxar reduced overall occurrences of ischemic events, first and subsequent (HR, 0.88; 95% CI, 0.80 to 0.98; P=0.02; NNT, 51). Also, there was a trend indicating that vorapaxar reduced the expanded endpoint, including revascularization and rehospitalization for recurrent ischemia (HR, 0.92; 95% CI, 0.84 to 1.01; P=0.09). Vorapaxar increased overall occurrences of moderate and severe Global Use of Strategies to Open Occluded Coronary Arteries bleeding (HR, 1.42; 95% CI, 1.21 to 1.66; P<0.001) and Thrombolysis in Myocardial Infarction clinically significant bleeding (HR, 1.550; 95% CI, 1.403 to 1.713; P<0.001).ConclusionsVorapaxar reduced overall occurrences of ischemic events, but increased bleeding. These exploratory findings broaden our understanding of vorapaxar's potential and expand our understanding of the value of capturing recurrent events.Clinical Trial Registration UrlClinicalTrials.gov. Unique identifier: NCT00527943.© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

30 keywords...

hide…