Journal article
Vorapaxar in the Secondary Prevention of Atherothrombotic Events
The New England journal of medicine, Vol.366(15), pp.1404-1413
04/12/2012
DOI: 10.1056/NEJMoa1200933
PMID: 22443427
Abstract
BACKGROUND
Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1.
METHODS
We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage.
RESULTS
At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001).
CONCLUSIONS
Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)
Details
- Title: Subtitle
- Vorapaxar in the Secondary Prevention of Atherothrombotic Events
- Creators
- David A. Morrow - Mass General BrighamEugene Braunwald - Brigham and Women's HospitalMarc P. Bonaca - Brigham and Women's HospitalSebastian F. Ameriso - Fundación para la Lucha contra las Enfermedades Neurológicas de la InfanciaAnthony J. Dalby - Milpark HospitalMary Polly Fish - Brigham and Women's HospitalKeith A. A. Fox - University of EdinburghLeslie J. Lipka - MSDXuan Liu - MSDJose Carlos Nicolau - Universidade de São PauloA. J. Oude Ophuis - Canisius-Wilhelmina ZiekenhuisErnesto Paolasso - Instituto de Investigaciones Clinicas RosarioBenjamin M. Scirica - Brigham and Women's HospitalJindrich Spinar - University Hospital BrnoPierre Theroux - Montreal Heart InstituteStephen D. Wiviott - Brigham and Women's HospitalJohn Strony - MSDSabina A. Murphy - Brigham and Women's HospitalTRA 2P–TIMI 50 Steering Committee and Investigators
- Contributors
- Phillip A Horwitz (Contributor) - University of Iowa, Cardiovascular Medicine
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.366(15), pp.1404-1413
- Publisher
- Massachusetts Medical Soc
- DOI
- 10.1056/NEJMoa1200933
- PMID
- 22443427
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Number of pages
- 10
- Grant note
- Merck; Merck & Company
- Language
- English
- Date published
- 04/12/2012
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359592302771
Metrics
5 Record Views