@article{84a8b053072b498cbcb555953a78f813,
title = "Vorapaxar in the secondary prevention of atherothrombotic events",
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.)",
author = "Morrow, {David A.} and Eugene Braunwald and Bonaca, {Marc P.} and Ameriso, {Sebastian F.} and Dalby, {Anthony J.} and Fish, {Mary Polly} and Fox, {Keith A.A.} and Lipka, {Leslie J.} and Xuan Liu and Nicolau, {Jos{\'e} Carlos} and Ophuis, {A. J.Oude} and Ernesto Paolasso and Scirica, {Benjamin M.} and Jindrich Spinar and Pierre Theroux and Wiviott, {Stephen D.} and John Strony and Murphy, {Sabina A.} and {TRA 2P–TIMI 50 Steering Committee and Investigators} and McCabe, {C. H.} and S. Morin and J. Lamp and E. Gershman and N. Deenadayalu and A. Skene and K. Hill and L. Bennett and F. Plat and G. Berman and A. Kilian and W. He and P. Aylward and Bassand, {J. P.} and A. Betriu and H. Bounameaux and R. Corbalan and M. Creager and {De Ferrari}, G. and M. Dellborg and Diehm, {C. H.} and R. Dietz and S. Goto and P. Grande and Gurbel, {Paul A.} and G. Hankey and D. Isaza and P. Jensen and R. Kiss and B. Lewis and P. Merlini and D. Moliterno and J. Morais and M. Nieminen and D. Nilsen and J. Olin and M. Pichler and Y. Shinohara and P. Teal and M. Tendera and L. Thomassen and {Van de Werf}, F. and H. White and R. Wilcox and M. Alberts and H. Diener and J. Mohr and M. Welch and E. Awtry and C. Berger and A. Desai and E. Gelfand and C. Ho and D. Leeman and M. Link and A. Norden and A. Pande and N. Rost and R. Ruberg and S. Silverman and A. Singhal and J. Vita and Frye, {R. L.} and Bailey, {K. R.} and J. Easton and J. Hochman and Steg, {P. G.} and F. Verheught and K. Lee and Mauro, {D. O.} and A. Centurion and O. Carlevaro and E. Cardozo and L. Cartasegna and N. Soccini and Farras, {H. A.} and {Molina Aguirre}, E. and E. Duronto and L. Arrechavala and R. Rey and A. Stilman and H. Fern{\'a}ndez and G. Marinsalta and J. Tartaglione and M. Chekherdemian and G. Povedano and E. Casares and P. Kantor and P. Reges and C. Cuneo and G. Martinez and I. MacKinnon and B. Bagnato and A. Fernandez and C. Funosas and A. Lozada and P. Barilati and J. Ferrari and N. Ferrari and J. Llanos and G. Casaccia and R. Giannaula and {Garc{\'i}a M{\'e}ndez}, C. and J. Cirio and {Garc{\'i}a D{\'a}vila}, C. and C. Estol and D. Chiezzo and J. Ramirez and S. Garrido and M. L{\'o}pez and M. Hominal and Bianchini, {M. V.} and M. Ramos and E. Verdini and G. Herrera and H. Monne and P. Ioli and Samudio, {M. A.} and {Rotta Escalante}, R. and A. Tarulla and E. Reich and G. Perez and R. Milesi and M. Berli and J. Marino and I. Funes and A. Prado and M. Bezi and R. Fernandez and M. Rojas and {Cimbaro Canella}, {J. P.} and {Galarza Salazan}, M. and D. Chew and L. Horsfall and A. Claxton and J. French and K. O'Brien and G. Nelson and A. Loxton and A. McCann and C. Downey and C. Aroney and P. Cleave and S. Worthley and A. Roach and J. Amerena and A. Long and P. Thompson and L. Ferguson and M. Fitzpatrick and M. Mackenzie and G. Youssef and H. Goldsmith and R. Jayasinghe and S. Quinlan and M. Arstall and J. Rose and J. Counsell and M. Martin and D. Crimmins and A. Slattery and C. Anderson and T. Paraskevaidis and S. Davis and G. Silver and Gerraty, {R. P.} and J. Gapper and G. Donnan and S. Petrolo and A. Whelan and G. Tulloch and B. Singh and Campo, {M. A.} and R. Dick and C. Savage and A. Hill and B. Conway and J. Waites and P. Keays and K. Kopp and D. Hainzer and A. Podczeck-Schweighofer and T. Priesnitz and H. Drexel and V. Hagspiel and B. Foeger and C. Hilbe and E. Trinka and D. Sinadinoska and E. Pilger and M. Brodmann and C. St{\"o}llberger and Jungbauer, {L. V.} and R. Koppensteiner and M. Hoke and W. Grisold and O. Berger and Gaul, {G. B.} and N. Fazekas and C. Wandaller and F. Stockenhuber and A. Rek and J. Willeit and A. Zangerle and S. Kiechl and W. Sturm and M. Theurl and F. Gruber and S. Schacherl and J. Auer and C. Primus and B. Eber and M. Ammer and Hofer, {J. F.} and H. Mayr and S. Moser and I. Hoellmueller and {Van der Werf}, F. and S. Motte and M. Jorion and H. Schro{\"e} and W. Zwinnen and F. Vermassen and M. Geenens and {De Wolf}, L. and C. Brik{\'e} and {De Deyn}, P. and P. Ongena and {De Klippel}, N. and K. Meeuwissen and P. Desfontaines",
year = "2012",
month = apr,
day = "12",
doi = "10.1056/NEJMoa1200933",
language = "English",
volume = "366",
pages = "1404--1413",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachusetts Medical Society",
number = "15",
}