Vorapaxar in the Secondary Prevention of Atherothrombotic Events
Por:
Morrow, DA, Braunwald, E, Bonaca, MP, Ameriso, SF, Dalby, AJ, Fish, MP, Fox, KAA, Lipka, LJ, Liu, X, Nicolau, JC, Ophuis, AJO, Paolasso, E, Scirica, BM, Spinar, J, Theroux, P, Wiviott, SD, Strony, J, Murphy, SA, Kuisevsky, J, TRA 2P-TIMI 50 Steering Comm Inves
Publicada:
12 abr 2012
Resumen:
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.)
Filiaciones:
Morrow, DA:
Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA
Braunwald, E:
Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA
Bonaca, MP:
Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA
Ameriso, SF:
FLENI, Neurol Res Inst, Buenos Aires, DF, Argentina
Dalby, AJ:
Milpark Hosp, Johannesburg, South Africa
Fish, MP:
Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA
Fox, KAA:
Univ Edinburgh, Div Cardiovasc Res, Edinburgh, Midlothian, Scotland
Lipka, LJ:
Merck Res Labs, Rahway, NJ USA
Liu, X:
Merck Res Labs, Rahway, NJ USA
Nicolau, JC:
Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil
Ophuis, AJO:
Canisius Wilhelmina Hosp, Nijmegen, Netherlands
Paolasso, E:
Inst Invest Clin Rosario, Rosario, Santa Fe, Argentina
Scirica, BM:
Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA
Spinar, J:
Masaryk Univ, Univ Hosp Brno, Brno, Czech Republic
Theroux, P:
Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada
Univ Montreal, Montreal, PQ, Canada
Wiviott, SD:
Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA
Strony, J:
Merck Res Labs, Rahway, NJ USA
Murphy, SA:
Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA
Kuisevsky, J:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Green Published
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