Sacco, Ralph L. and Diener, Hans-Christoph and Yusuf, Salim and Cotton, Daniel and Ounpuu, Stephanie and Lawton, William A. and Palesch, Yuko and Martin, Renée H. and Albers, Gregory W. and Bath, Philip M.W. and Bornstein, Natan and Chan, Bernard P.L. and Chen, Sien-Tsong and Cunha, Luis and Dahlöf, Björn and De Keyser, Jacques and Donnan, Geoffrey A. and Estol, Conrado and Gorelick, Philip and Gu, Vivian and Hermansson, Karin and Hillbrich, Lutz and Kaste, Markku and Lu, Chuanzhen and Machnig, Thomas and Pais, Prem and Roberts, Robin and Skvortsova, Veronika and Teal, Philip and Toni, Danilo and Vandermaelen, Cam and Voight, Thor and Weber, Michael and Yoon, Byung-Woo
Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke.
New England Journal of Medicine, 359
Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared
the efficacy and safety of two antiplatelet regimens — aspirin plus extendedrelease
dipyridamole (ASA–ERDP) versus clopidogrel.
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.
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).
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. (ClinicalTrials.gov number, NCT00153062.)
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