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Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

Sacco, Ralph L.; Diener, Hans-Christoph; Yusuf, Salim; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A.; Palesch, Yuko; Martin, Renée H.; Albers, Gregory W.; Bath, Philip M.W.; Bornstein, Natan; Chan, Bernard P.L.; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A.; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hillbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; Vandermaelen, Cam; Voight, Thor; Weber, Michael; Yoon, Byung-Woo


Ralph L. Sacco

Hans-Christoph Diener

Salim Yusuf

Daniel Cotton

Stephanie Ounpuu

William A. Lawton

Yuko Palesch

Renée H. Martin

Gregory W. Albers

Philip M.W. Bath

Natan Bornstein

Bernard P.L. Chan

Sien-Tsong Chen

Luis Cunha

Björn Dahlöf

Jacques De Keyser

Geoffrey A. Donnan

Conrado Estol

Philip Gorelick

Vivian Gu

Karin Hermansson

Lutz Hillbrich

Markku Kaste

Chuanzhen Lu

Thomas Machnig

Prem Pais

Robin Roberts

Veronika Skvortsova

Philip Teal

Danilo Toni

Cam Vandermaelen

Thor Voight

Michael Weber

Byung-Woo Yoon


Background: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens — aspirin plus extended release dipyridamole (ASA–ERDP) versus clopidogrel.
Methods: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned.
Results: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA–ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA–ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA–ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial haemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA–ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).
Conclusions: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA–ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke.

Journal Article Type Article
Publication Date Sep 18, 2008
Journal New England Journal of Medicine
Print ISSN 0028-4793
Electronic ISSN 0028-4793
Publisher Massachusetts Medical Society
Peer Reviewed Peer Reviewed
Volume 359
Issue 12
Pages 1238-1251
APA6 Citation Sacco, R. L., Diener, H., Yusuf, S., Cotton, D., Ounpuu, S., Lawton, W. A., …Yoon, B. (2008). Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. New England Journal of Medicine, 359(12), (1238-1251). doi:10.1056/NEJMoa0805002. ISSN 0028-4793
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Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
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