Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke.
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. (ClinicalTrials.gov number, NCT00153062.)
Sacco
Ralph L
RL
Miller School of Medicine, University of Miami, Miami, USA.
Diener
Hans-Christoph
HC
Yusuf
Salim
S
Cotton
Daniel
D
Ounpuu
Stephanie
S
Lawton
William A
WA
Palesch
Yuko
Y
Martin
Reneé H
RH
Albers
Gregory W
GW
Bath
Philip
P
Bornstein
Natan
N
Chan
Bernard P L
BP
Chen
Sien-Tsong
ST
Cunha
Luis
L
Dahlöf
Björn
B
De Keyser
Jacques
J
Donnan
Geoffrey A
GA
Estol
Conrado
C
Gorelick
Philip
P
Gu
Vivian
V
Hermansson
Karin
K
Hilbrich
Lutz
L
Kaste
Markku
M
Lu
Chuanzhen
C
Machnig
Thomas
T
Pais
Prem
P
Roberts
Robin
R
Skvortsova
Veronika
V
Teal
Philip
P
Toni
Danilo
D
Vandermaelen
Cam
C
Voigt
Thor
T
Weber
Michael
M
Yoon
Byung-Woo
BW