Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

Ralph L. Sacco, Hans Christoph Diener, Salim Yusuf, Daniel Cotton, Stephanie Ôunpuu, William A. Lawton, Yuko Palesch, Reneé H. Martin, Gregory W. Albers, Philip 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 GuKarin Hermansson, Lutz Hilbrich, Markku Kaste, Chuanzhen Lu, Thomas Machnig, Prem Pais, Robin Roberts, Veronika Skvortsova, Philip Teal, Danilo Toni, Cam Vander Maelen, Thor Voigt, Michael Weber, Byung Woo Yoon

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700 Scopus citations

Abstract

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 hemorrhage (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.

Original languageEnglish (US)
Pages (from-to)1238-1251
Number of pages14
JournalNew England Journal of Medicine
Volume359
Issue number12
DOIs
StatePublished - Sep 18 2008

ASJC Scopus subject areas

  • Medicine(all)

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    Sacco, R. L., Diener, H. C., Yusuf, S., Cotton, D., Ôunpuu, S., Lawton, W. A., Palesch, Y., Martin, R. H., Albers, G. W., Bath, P., Bornstein, N., Chan, B. P. L., Chen, S. T., Cunha, L., Dahlöf, B., De Keyser, J., Donnan, G. A., Estol, C., Gorelick, P., ... Yoon, B. W. (2008). Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. New England Journal of Medicine, 359(12), 1238-1251. https://doi.org/10.1056/NEJMoa0805002