Abstract
BACKGROUND: Clinical 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 RESULTS: TRACER 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; PP<0.001).
CONCLUSIONS: Vorapaxar 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.
Document Type
Article
Publication Date
8-2014
Digital Object Identifier (DOI)
http://dx.doi.org/10.1161/JAHA.114.001032
Funding Information
The TRACER trial was funded by Merck & Co, Inc. (Whitehouse Station, NJ; ClinicalTrials.gov Identifier: NCT00527943).
Repository Citation
White, Harvey D.; Huang, Zhen; Tricoci, Pierluigi; Van de Werf, Frans; Wallentin, Lars; Lokhnygina, Yuliya; Moliterno, David J.; Aylward, Philip E.; Mahaffey, Kenneth W.; and Armstrong, Paul W., "Reduction in Overall Occurrences of Ischemic Events with Vorapaxar: Results from TRACER" (2014). Internal Medicine Faculty Publications. 78.
https://uknowledge.uky.edu/internalmedicine_facpub/78
Notes/Citation Information
Published in Journal of the American Heart Association, v. 3, no. 4, article e001032, p. 1-9.
© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.