Reduction in overall occurrences of ischemic events with vorapaxar: results from TRACER

Harvey D White; Zhen Huang; Pierluigi Tricoci; Frans Van de Werf; Lars Wallentin; Yuliya Lokhnygina; David J Moliterno; Philip E Aylward; Kenneth W Mahaffey; Paul W Armstrong

doi:10.1161/JAHA.114.001032

Reduction in overall occurrences of ischemic events with vorapaxar: results from TRACER

J Am Heart Assoc. 2014 Jul 10;3(4):e001032. doi: 10.1161/JAHA.114.001032.

Authors

Affiliations

¹ Green Lane Cardiovascular Service, Auckland City Hospital and Auckland University, Auckland, New Zealand (H.D.W.).
² Duke Clinical Research Institute, Durham, NC (Z.H., P.T., Y.L.).
³ Department of Cardiology, University of Leuven, Leuven, Belgium (F.V.W.).
⁴ Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden (L.W.).
⁵ Gill Heart Institute and Division of Cardiovascular Medicine, University of Kentucky, Lexington, KY (D.J.M.).
⁶ SAHMRI, Flinders University and Medical Center, Adelaide, Australia (P.E.A.).
⁷ Department of Medicine, Stanford University, Stanford, CA (K.W.M.).
⁸ Division of Cardiology, University of Alberta, Edmonton, Canada (P.W.A.).

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; 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.

Keywords: acute coronary syndromes; recurrent events; vorapaxar.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Acute Coronary Syndrome / drug therapy*
Aged
Cardiovascular Diseases / prevention & control
Double-Blind Method
Female
Hemorrhage / chemically induced
Humans
Ischemia / prevention & control*
Lactones / therapeutic use*
Male
Middle Aged
Myocardial Infarction / prevention & control*
Platelet Aggregation Inhibitors / therapeutic use*
Proportional Hazards Models
Pyridines / therapeutic use*
Recurrence
Secondary Prevention*
Stroke / prevention & control*
Treatment Outcome

Substances

Lactones
Platelet Aggregation Inhibitors
Pyridines
vorapaxar

Associated data

ClinicalTrials.gov/NCT00527943