Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
Open accessAbstract
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.)
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Given the high prevalence of hypercholesterolaemia in stroke patients, blood lipids might be a suitable target for neurorestorative therapies.
“In view of the high prevalence of hypercholesterolaemia in stroke patients, blood lipids might be a suitable target for neurorestorative therapies.”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [81]
In patients with transient ischaemic attack or ischaemic stroke, dipyridamole plus aspirin versus clopidogrel alone had similar rates of recurrent stroke, including haemorrhagic stroke (916 vs 898; HR 1.01, 95% CI 0.92-1.11), with a higher frequency of major haemorrhagic events with dipyridamole plus aspirin (4.1% vs 3.6%); stroke, myocardial infarction, and vascular death occurred in 13.1% in
“In patients with transient ischaemic attack or ischaemic stroke, a direct comparison of dipyridamole plus aspirin vs. clopidogrel alone 508 showed that the two regimens had similar rates of recurrent stroke, including haemorrhagic stroke (916 vs. 898; HR 1.01, 95% CI 0.92-1.11).There was a higher frequency of major haemorrhagic events with dipyridamole plus aspirin (4.1% vs. 3.6%).Stroke,”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [508]
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- Authors
- 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., Gu, V., Hermansson, K., Hilbrich, L., Kaste, M., Lu, C., Machnig, T., Pais, P., Roberts, R., Skvortsova, V., Teal, P., Toni, D., VanderMaelen, C., Voigt, T., Weber, M., & Yoon, B.-W.
- Affiliations
- University of Miami (US)
- Boehringer Ingelheim (Germany) (DE)
- University of Nottingham (GB)
- University of British Columbia (CA)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2008-09-18
- Volume
- 359
- Issue
- 12
- Pages
- 1238-1251
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC2714259
- OpenAlex
- W2397867274
- Cited by
- 961
- References
- 34
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 27 · 2023: 24 · 2022: 43 · 2021: 40 · 2020: 32 · 2019: 45 · 2018: 48 · 2017: 54 · 2016: 46 · 2015: 53 · 2014: 57 · 2013: 68 · 2012: 105
- FWCI
- 68.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, other-oa)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
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- Nottingham ePrints (University of Nottingham) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Bristol-Myers Squibb
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- Daiichi-Sankyo
- Novo Nordisk
- Servier
- National Institutes of Health (5k23ns054084-05)
- Bayer Vital
- National Institute of Neurological Disorders and Stroke (K23-NS054084)
- Daiichi Sankyo Europe
- Cilag
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- stroke recurrence, ischemic stroke, aspirin, extended-release dipyridamole, clopidogrel, antiplatelet therapy, non-inferiority, intracranial hemorrhage, secondary stroke prevention, vascular death, myocardial infarction, net benefit, factorial trial, comparative efficacy and safety, 10-year follow-up
- MeSH terms
- Clopidogrel, Telmisartan, Aged, Angiotensin-Converting Enzyme Inhibitors, Aspirin, Benzimidazoles, Benzoates, Brain Ischemia, Delayed-Action Preparations, Dipyridamole, Double-Blind Method, Drug Therapy, Combination, Factor Analysis, Statistical, Female, Hemorrhage, Humans, Male, Middle Aged, Myocardial Infarction, Platelet Aggregation Inhibitors, Risk, Ticlopidine, Vascular Diseases, Proportional Hazards Models, Stroke, Kaplan-Meier Estimate, Secondary Prevention
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