TY - JOUR
T1 - Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
AU - Sacco, Ralph L
AU - Diener, Hans-Christoph
AU - Yusuf, Salim
AU - Cotton, Daniel
AU - Ounpuu, Stephanie
AU - Lawton, William A
AU - Palesch, Yuko
AU - Martin, Reneé H
AU - Albers, Gregory W
AU - Bath, Philip
AU - Bornstein, Natan
AU - Chan, Bernard P L
AU - Chen, Sien-Tsong
AU - Cunha, Luis
AU - Dahlöf, Björn
AU - De Keyser, Jacques
AU - Donnan, Geoffrey A
AU - Estol, Conrado
AU - Gorelick, Philip
AU - Gu, Vivian
AU - Hermansson, Karin
AU - Hilbrich, Lutz
AU - Kaste, Markku
AU - Lu, Chuanzhen
AU - Machnig, Thomas
AU - Pais, Prem
AU - Roberts, Robin
AU - Skvortsova, Veronika
AU - Teal, Philip
AU - Toni, Danilo
AU - Vandermaelen, Cam
AU - Voigt, Thor
AU - Weber, Michael
AU - Yoon, Byung-Woo
AU - PRoFESS Study Group
A2 - Skogar, Örjan
N1 - 2008 Massachusetts Medical Society
PY - 2008/9/18
Y1 - 2008/9/18
N2 - 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.)
AB - 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.)
KW - Aged
KW - Angiotensin-Converting Enzyme Inhibitors/therapeutic use
KW - Aspirin/administration & dosage
KW - Benzimidazoles/therapeutic use
KW - Benzoates/therapeutic use
KW - Brain Ischemia/epidemiology
KW - Clopidogrel
KW - Delayed-Action Preparations
KW - Dipyridamole/adverse effects
KW - Double-Blind Method
KW - Drug Therapy, Combination
KW - Factor Analysis, Statistical
KW - Female
KW - Hemorrhage/chemically induced
KW - Humans
KW - Kaplan-Meier Estimate
KW - Male
KW - Middle Aged
KW - Myocardial Infarction/epidemiology
KW - Platelet Aggregation Inhibitors/administration & dosage
KW - Proportional Hazards Models
KW - Risk
KW - Secondary Prevention
KW - Stroke/drug therapy
KW - Telmisartan
KW - Ticlopidine/adverse effects
KW - Vascular Diseases/mortality
U2 - 10.1056/NEJMoa0805002
DO - 10.1056/NEJMoa0805002
M3 - Article
C2 - 18753638
SN - 0028-4793
VL - 359
SP - 1238
EP - 1251
JO - The New England journal of medicine
JF - The New England journal of medicine
IS - 12
ER -