Circulation. 2003;108:1682-1687
Published online before print September 22, 2003, doi: 10.1161/01.CIR.0000091201.39590.CB
Published online before print September 22, 2003, doi: 10.1161/01.CIR.0000091201.39590.CB
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(Circulation. 2003;108:1682.)
© 2003 American Heart Association, Inc.
Clinical Investigations |
Effects of Aspirin Dose When Used Alone or in Combination With Clopidogrel in Patients With Acute Coronary Syndromes
Observations From the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Study
From the Department of Cardiology (P.J.G.P.), Academic Medical Center, Amsterdam, the Netherlands; Canadian Cardiovascular Collaboration Project Office (S.R.M., F.Z., S.Y.), McMaster University, Hamilton, Ontario, Canada; Royal Infirmary of Edinburgh (K.A.A.F.), Edinburgh, UK; Lady Davis Carmel Medical Center (B.S.L.), Haifa, Israel; Division of Cardiovascular Diseases (S.L.K.), Mayo Clinic and Foundation, Rochester, Minn; Estudios Cardiologicos Latinoamerica (R.D.), Instituto Cardiovascular de Rosario, Argentina; Department of Medicine (P.J.C.), University of Cape Town, South Africa; and Unidad Coronaria (V.V.), Hospital Universitario Dr Peset, Valencia, Spain.
Correspondence to Salim Yusuf, Canadian Cardiovascular Collaboration Project Office, Population Health Research Institute, McMaster University, Hamilton General Hospital, 237 Barton Street East, Hamilton, ON L8L 2X2, Canada. E-mail yusufs{at}mcmaster.ca
Received November 22, 2002; de novo received March 6, 2003; revision received July 11, 2003; accepted July 11, 2003.
Abstract
Background— We studied the benefits and risks of adding clopidogrel to different doses of aspirin in the treatment of patients with acute coronary syndrome (ACS).
Methods and Results— In the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial, 12 562 patients with ACS using aspirin, 75 to 325 mg daily, were randomized to clopidogrel or placebo for up to 1 year. In this analysis, patients were divided into the following 3 aspirin dose groups: 
100 mg, 101 through 199 mg, and 
200 mg. The combined incidence of cardiovascular death, myocardial infarction, or stroke was reduced by clopidogrel regardless of aspirin dose, as follows: 100 mg, 10.5% versus 8.6% (relative risk [RR], 0.81 [95% CI, 0.68 to 0.97]); 101 to 199 mg, 9.8% versus 9.5% (RR, 0.97 [95% CI 0.77 to 1.22]); and 200 mg, 13.6% versus 9.8% (RR, 0.71 [95% CI, 0.59 to 0.85]). The incidence of major bleeding increased with increasing aspirin dose both in the placebo group (1.9%, 2.8%, and 3.7%, respectively; P=0.0001) and the clopidogrel group (3.0%, 3.4%, and 4.9%, respectively; P=0.0009); thus, the excess risk with clopidogrel was 1.1%, 1.2%, and 1.2%, respectively. The adjusted hazard ratio for major bleeding for the highest versus the lowest dose of aspirin was 1.9 (95% CI 1.29 to 2.72) in the placebo group, 1.6 (95% CI 1.19 to 2.23) in the clopidogrel group, and 1.7 (95% CI 1.36 to 2.20) in the combined group.
Conclusions— In patients with ACS, adding clopidogrel to aspirin is beneficial regardless of aspirin dose. Bleeding risks increase with increasing aspirin dose, with or without clopidogrel, without any increase in efficacy. Our findings suggest that the optimal daily dose of aspirin may be between 75 and 100 mg, with or without clopidogrel.
Key Words: aspirin • coronary disease • angina • platelets • thrombosis
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P. Eriksson Reply: Long-term clopidogrel following PCI: marginal antithrombotic effects are offset by increased bleeding risks Eur. Heart J., December 1, 2004; 25(23): 2170 - 2171. [Full Text] [PDF]
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C. M. Gibson, R. L. Dumaine, E. V. Gelfand, S. A. Murphy, D. A. Morrow, S. D. Wiviott, R. P. Giugliano, C. P. Cannon, E. M. Antman, E. Braunwald, et al. Association of glomerular filtration rate on presentation with subsequent mortality in non-ST-segment elevation acute coronary syndrome; observations in 13307 patients in five TIMI trials Eur. Heart J., November 2, 2004; 25(22): 1998 - 2005. [Abstract] [Full Text] [PDF]
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S. Gruner, M. Prostredna, B. Aktas, A. Moers, V. Schulte, T. Krieg, S. Offermanns, B. Eckes, and B. Nieswandt Anti-Glycoprotein VI Treatment Severely Compromises Hemostasis in Mice With Reduced {alpha}2{beta}1 Levels or Concomitant Aspirin Therapy Circulation, November 2, 2004; 110(18): 2946 - 2951. [Abstract] [Full Text] [PDF]
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J. W. Newburger, M. Takahashi, M. A. Gerber, M. H. Gewitz, L. Y. Tani, J. C. Burns, S. T. Shulman, A. F. Bolger, P. Ferrieri, R. S. Baltimore, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Statement for Health Professionals From the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association Circulation, October 26, 2004; 110(17): 2747 - 2771. [Abstract] [Full Text] [PDF]
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S. P. Schulman Antiplatelet Therapy in Non-ST-Segment Elevation Acute Coronary Syndromes JAMA, October 20, 2004; 292(15): 1875 - 1882. [Abstract] [Full Text] [PDF]
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C. Patrono, B. Coller, G. A. FitzGerald, J. Hirsh, and G. Roth Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 234S - 264S. [Abstract] [Full Text] [PDF]
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J. J. Popma, P. Berger, E. M. Ohman, R. A. Harrington, C. Grines, and J. I. Weitz Antithrombotic Therapy During Percutaneous Coronary Intervention: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 576S - 599S. [Abstract] [Full Text] [PDF]
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E. M Antman The re-emergence of anticoagulation in coronary disease Eur. Heart J. Suppl., April 1, 2004; 6(suppl_B): B2 - B8. [Abstract] [Full Text] [PDF]
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D. L. Bhatt Aspirin resistance: more than just a laboratory curiosity J. Am. Coll. Cardiol., March 17, 2004; 43(6): 1127 - 1129. [Full Text] [PDF]
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D. L. Connolly, A. Choudhury, R. C. Davis, and G. Y. H. Lip A randomized trial of aspirin on the risk of embolic events in patients with infective endocarditis J. Am. Coll. Cardiol., March 17, 2004; 43(6): 1134 - 1135. [Full Text] [PDF]
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Minerva BMJ, October 18, 2003; 327(7420): 938 - 938. [Full Text] [PDF]
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