Open AccessReduction in Overall Occurrences of Ischemic Events With Vorapaxar: Results From TRACER
Author(s) -
White Harvey D.,
Huang Zhen,
Tricoci Pierluigi,
Van de Werf Frans,
Wallentin Lars,
Lokhnygina Yuliya,
Moliterno David J.,
Aylward Philip E.,
Mahaffey Kenneth W.,
Armstrong Paul W.
Publication year - 2014
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.114.001032
Subject(s) - medicine , cardiology , reduction (mathematics) , ischemic stroke , tracer , ischemia , physics , geometry , mathematics , nuclear physics
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; P <0.001) and Thrombolysis in Myocardial Infarction clinically significant bleeding ( HR, 1.550; 95% CI, 1.403 to 1.713; P <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. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00527943.