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Previous Volume 352:1179-1189 March 24, 2005 Number 12 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Lange, R. A. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death.

Methods We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel (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 after the start of study medication. The primary efficacy end point was a composite of an occluded infarct-related artery (defined by a Thrombolysis in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography.

Results The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy (95 percent confidence interval, 24 to 47 percent; P<0.001). By 30 days, clopidogrel therapy reduced the odds of the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent (from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups.

Conclusions In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery 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.

Full Text of this Article

Related Letters:

Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction
Chua D., Lo C., Babor E.-M., Sabatine M. S., Cannon C. P., Braunwald E., the CLARITY–TIMI 28 Investigators
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N Engl J Med 2005; 352:2647-2648, Jun 23, 2005. Correspondence

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• Birnbaum, Y., Lin, Y., Ye, Y., Martinez, J. D., Huang, M.-H., Lui, C. Y., Perez-Polo, J. R, Uretsky, B. F. (2007). Aspirin before reperfusion blunts the infarct size limiting effect of atorvastatin. Am. J. Physiol. Heart Circ. Physiol. 292: H2891-H2897 [Abstract] [Full Text]  
• Spinler, S. A. (2007). Managing acute coronary syndrome: Evidence-based approaches. Am J Health Syst Pharm 64: S14-S24 [Abstract] [Full Text]  
• Alexander, K. P., Newby, L. K., Cannon, C. P., Armstrong, P. W., Gibler, W. B., Rich, M. W., Van de Werf, F., White, H. D., Weaver, W. D., Naylor, M. D., Gore, J. M., Krumholz, H. M., Ohman, E. M. (2007). Acute Coronary Care in the Elderly, Part I: Non-ST-Segment-Elevation Acute Coronary Syndromes: A Scientific Statement for Healthcare Professionals From the American Heart Association Council on Clinical Cardiology: In Collaboration With the Society of Geriatric Cardiology. Circulation 115: 2549-2569 [Abstract] [Full Text]  
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• Meadows, T. A., Bhatt, D. L. (2007). Clinical Aspects of Platelet Inhibitors and Thrombus Formation. Circ. Res. 100: 1261-1275 [Abstract] [Full Text]