Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction with ST-Segment Elevation
Marc S. Sabatine, M.D., M.P.H., Christopher P. Cannon, M.D., C. Michael Gibson, M.D., Jose L. López-Sendón, M.D., Gilles Montalescot, M.D., Pierre Theroux, M.D., Marc J. Claeys, M.D., Ph.D., Frank Cools, M.D., Karen A. Hill, B.A., Allan M. Skene, Ph.D., Carolyn H. McCabe, B.S., Eugene Braunwald, M.D., for the CLARITYTIMI 28 Investigators
Background A substantial proportion of patients receiving fibrinolytictherapy for myocardial infarction with ST-segment elevationhave inadequate reperfusion or reocclusion of the infarct-relatedartery, leading to an increased risk of complications and death.
Methods We enrolled 3491 patients, 18 to 75 years of age, whopresented within 12 hours after the onset of an ST-elevationmyocardial infarction and randomly assigned them to receiveclopidogrel (300-mg loading dose, followed by 75 mg once daily)or placebo. Patients received a fibrinolytic agent, aspirin,and when appropriate, heparin (dispensed according to body weight)and were scheduled to undergo angiography 48 to 192 hours afterthe start of study medication. The primary efficacy end pointwas a composite of an occluded infarct-related artery (definedby a Thrombolysis in Myocardial Infarction flow grade of 0 or1) on angiography or death or recurrent myocardial infarctionbefore angiography.
Results The rates of the primary efficacy end point were 21.7percent in the placebo group and 15.0 percent in the clopidogrelgroup, representing an absolute reduction of 6.7 percentagepoints in the rate and a 36 percent reduction in the odds ofthe end point with clopidogrel therapy (95 percent confidenceinterval, 24 to 47 percent; P<0.001). By 30 days, clopidogreltherapy reduced the odds of the composite end point of deathfrom cardiovascular causes, recurrent myocardial infarction,or recurrent ischemia leading to the need for urgent revascularizationby 20 percent (from 14.1 to 11.6 percent, P=0.03). The ratesof major bleeding and intracranial hemorrhage were similar inthe two groups.
Conclusions In patients 75 years of age or younger who havemyocardial infarction with ST-segment elevation and who receiveaspirin and a standard fibrinolytic regimen, the addition ofclopidogrel improves the patency rate of the infarct-relatedartery and reduces ischemic complications.
Source Information
From the TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (M.S.S., C.P.C., C.M.G., C.H.M., E.B.); Hospital Universitario Gregorio Marañon, Madrid (J.L.L.-S.); Institut de Cardiologie, Hôpital Pitié-Salpêtrière, Paris (G.M.); the Montreal Heart Institute, Montreal (P.T.); the Department of Cardiology, University Hospital Antwerp, Edegem, Belgium (M.J.C.); Academisch Ziekenhuis Klina, Brasschaat, Belgium (F.C.); and Nottingham Clinical Research Group, Nottingham, United Kingdom (K.A.H., A.M.S.). This article was published at www.nejm.org on March 9, 2005.
Address reprint requests to Dr. Sabatine at the TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115, or at msabatine{at}partners.org.
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