Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
(2008) In The New England journal of medicine 359(12). p.1238-1251- 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... (More)
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.)
(Less)
- author
- contributor
- Skogar, Örjan
LU
- author collaboration
- publishing date
- 2008-09-18
- type
- Contribution to journal
- publication status
- published
- keywords
- Aged, Angiotensin-Converting Enzyme Inhibitors/therapeutic use, Aspirin/administration & dosage, Benzimidazoles/therapeutic use, Benzoates/therapeutic use, Brain Ischemia/epidemiology, Clopidogrel, Delayed-Action Preparations, Dipyridamole/adverse effects, Double-Blind Method, Drug Therapy, Combination, Factor Analysis, Statistical, Female, Hemorrhage/chemically induced, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Myocardial Infarction/epidemiology, Platelet Aggregation Inhibitors/administration & dosage, Proportional Hazards Models, Risk, Secondary Prevention, Stroke/drug therapy, Telmisartan, Ticlopidine/adverse effects, Vascular Diseases/mortality
- in
- The New England journal of medicine
- volume
- 359
- issue
- 12
- pages
- 1238 - 1251
- publisher
- Massachusetts Medical Society
- external identifiers
-
- pmid:18753638
- scopus:51449116270
- ISSN
- 0028-4793
- DOI
- 10.1056/NEJMoa0805002
- language
- English
- LU publication?
- no
- additional info
- 2008 Massachusetts Medical Society
- id
- 3d603553-f48a-467b-bfa9-efcd38d88fdb
- date added to LUP
- 2024-05-08 15:06:52
- date last changed
- 2024-12-20 06:25:55
@article{3d603553-f48a-467b-bfa9-efcd38d88fdb,
abstract = {{<p>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.</p><p>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.</p><p>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).</p><p>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.)</p>}},
author = {{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, Reneé H and Albers, Gregory W and Bath, Philip 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 Hilbrich, 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 Voigt, Thor and Weber, Michael and Yoon, Byung-Woo}},
issn = {{0028-4793}},
keywords = {{Aged; Angiotensin-Converting Enzyme Inhibitors/therapeutic use; Aspirin/administration & dosage; Benzimidazoles/therapeutic use; Benzoates/therapeutic use; Brain Ischemia/epidemiology; Clopidogrel; Delayed-Action Preparations; Dipyridamole/adverse effects; Double-Blind Method; Drug Therapy, Combination; Factor Analysis, Statistical; Female; Hemorrhage/chemically induced; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction/epidemiology; Platelet Aggregation Inhibitors/administration & dosage; Proportional Hazards Models; Risk; Secondary Prevention; Stroke/drug therapy; Telmisartan; Ticlopidine/adverse effects; Vascular Diseases/mortality}},
language = {{eng}},
month = {{09}},
number = {{12}},
pages = {{1238--1251}},
publisher = {{Massachusetts Medical Society}},
series = {{The New England journal of medicine}},
title = {{Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke}},
url = {{http://dx.doi.org/10.1056/NEJMoa0805002}},
doi = {{10.1056/NEJMoa0805002}},
volume = {{359}},
year = {{2008}},
}