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Effect of clopidogrel added to aspirin in patients with atrial fibrillation
journal contribution
posted on 2009-05-14, 00:00 authored by S J Connolly, S Yusuf, J Camm, S Chrolavicius, P Commerford, M Flather, R G Hart, S H Hohnloser, C Joyner, M Pfeffer, C Gaudin, M Blumenthal, C Marchese, J Pogue, R Hart, S Hohnloser, I Anand, H Arthur, A Avezum, A Budaj, L Ceremuzynski, R De Caterina, R Diaz, P Dorian, G Flaker, K A A Fox, M G Franzosi, S Goldhaber, S Golitsyn, C Granger, D Halon, A Hermosillo, D Hunt, P Jansky, N Karatzas, M Keltai, O Kozan, F Lanas, P Lau, J Y Le Heuzey, B S Lewis, J Morais, C Morillo, E Paolasso, R J Peters, M Pfisterer, L Piegas, A Pipilis, E Sitkei, K Swedberg, M Talajic, V Valentin, W Van Mieghem, J Varigos, S Ameriso, M Atra, O Berwanger, C Bonilla, N Bornstein, T Chamiec, Y K Chan, Y Cottin, L Csiba, J Cybulski, A Czepiel, H De Raedt, H Dvorakova, J Eikelboom, O Ergene, G Fodor, M Galli, E Gardinale, B Gross, P Goodfield, O Happola, J Healey, D Himbert, F Jacobsson, P Kalvach, B Kies, M Laine, A Lam, S Lewis, D Leys, A P Maggioni, A Massaro, B M Mayosi, B NorrvingBACKGROUND
Vitamin K antagonists reduce the risk of stroke in patients with atrial fibrillation but are considered unsuitable in many patients, who usually receive aspirin instead. We investigated the hypothesis that the addition of clopidogrel to aspirin would reduce the risk of vascular events in patients with atrial fibrillation.
METHODS
A total of 7554 patients with atrial fibrillation who had an increased risk of stroke and for whom vitamin K–antagonist therapy was unsuitable were randomly assigned to receive clopidogrel (75 mg) or placebo, once daily, in addition to aspirin. The primary outcome was the composite of stroke, myocardial infarction, non–central nervous system systemic embolism, or death from vascular causes.
RESULTS
At a median of 3.6 years of follow-up, major vascular events had occurred in 832 patients receiving clopidogrel (6.8% per year) and in 924 patients receiving placebo (7.6% per year) (relative risk with clopidogrel, 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.01). The difference was primarily due to a reduction in the rate of stroke with clopidogrel. Stroke occurred in 296 patients receiving clopidogrel (2.4% per year) and 408 patients receiving placebo (3.3% per year) (relative risk, 0.72; 95% CI, 0.62 to 0.83; P<0.001). Myocardial infarction occurred in 90 patients receiving clopidogrel (0.7% per year) and in 115 receiving placebo (0.9% per year) (relative risk, 0.78; 95% CI, 0.59 to 1.03; P=0.08). Major bleeding occurred in 251 patients receiving clopidogrel (2.0% per year) and in 162 patients receiving placebo (1.3% per year) (relative risk, 1.57; 95% CI, 1.29 to 1.92; P<0.001).
CONCLUSIONS
In patients with atrial fibrillation for whom vitamin K–antagonist therapy was unsuitable, the addition of clopidogrel to aspirin reduced the risk of major vascular events, especially stroke, and increased the risk of major hemorrhage. (ClinicalTrials.gov number, NCT00249873opens in new tab.)
Vitamin K antagonists reduce the risk of stroke in patients with atrial fibrillation but are considered unsuitable in many patients, who usually receive aspirin instead. We investigated the hypothesis that the addition of clopidogrel to aspirin would reduce the risk of vascular events in patients with atrial fibrillation.
METHODS
A total of 7554 patients with atrial fibrillation who had an increased risk of stroke and for whom vitamin K–antagonist therapy was unsuitable were randomly assigned to receive clopidogrel (75 mg) or placebo, once daily, in addition to aspirin. The primary outcome was the composite of stroke, myocardial infarction, non–central nervous system systemic embolism, or death from vascular causes.
RESULTS
At a median of 3.6 years of follow-up, major vascular events had occurred in 832 patients receiving clopidogrel (6.8% per year) and in 924 patients receiving placebo (7.6% per year) (relative risk with clopidogrel, 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.01). The difference was primarily due to a reduction in the rate of stroke with clopidogrel. Stroke occurred in 296 patients receiving clopidogrel (2.4% per year) and 408 patients receiving placebo (3.3% per year) (relative risk, 0.72; 95% CI, 0.62 to 0.83; P<0.001). Myocardial infarction occurred in 90 patients receiving clopidogrel (0.7% per year) and in 115 receiving placebo (0.9% per year) (relative risk, 0.78; 95% CI, 0.59 to 1.03; P=0.08). Major bleeding occurred in 251 patients receiving clopidogrel (2.0% per year) and in 162 patients receiving placebo (1.3% per year) (relative risk, 1.57; 95% CI, 1.29 to 1.92; P<0.001).
CONCLUSIONS
In patients with atrial fibrillation for whom vitamin K–antagonist therapy was unsuitable, the addition of clopidogrel to aspirin reduced the risk of major vascular events, especially stroke, and increased the risk of major hemorrhage. (ClinicalTrials.gov number, NCT00249873opens in new tab.)
History
Journal
New England journal of medicineVolume
360Issue
20Pagination
2066 - 2078Publisher
Massachusetts Medical SocietyLocation
Waltham, Mass.Publisher DOI
ISSN
0028-4793Language
EnglishPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2009, Massachusetts Medical SocietyUsage metrics
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No categories selectedKeywords
Science & TechnologyLife Sciences & BiomedicineMedicine, General & InternalGeneral & Internal MedicineStrokeCoronary diseaseMyocardial infarctionArrhythmiasPacemakersACUTE CORONARY SYNDROMESANTITHROMBOTIC THERAPYORAL ANTICOAGULATIONPLATELET ACTIVATIONCONTROLLED-TRIALVASCULAR EVENTSWARFARINTHROMBOGENESISRISKACTIVE Investigators
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