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Dipyridamole plus aspirin versus aspirin alone in secondary prevention after TIA or stroke: a meta-analysis by risk
  1. P H A Halkes1,
  2. L J Gray2,
  3. P M W Bath2,
  4. H-C Diener3,
  5. B Guiraud-Chaumeil4,
  6. F M Yatsu5,
  7. A Algra1
  1. 1
    Department of Neurology, Rudolf Magnus Institute of Neuroscience and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2
    The University of Nottingham, Nottingham, UK
  3. 3
    The University of Essen, Essen, Germany
  4. 4
    C H U de Toulouse-Purpan, Toulouse, France
  5. 5
    The University of Texas, Houston, USA
  1. Professor P M W Bath, Division of Stroke Medicine, University of Nottingham City Hospital Campus, Nottingham NG5 1PB, UK; philip.bath{at}


Objectives: To study the effect of combination therapy with aspirin and dipyridamole (A+D) over aspirin alone (ASA) in secondary prevention after transient ischaemic attack (TIA) or minor stroke of presumed arterial origin and to perform subgroup analyses to identify patients that might benefit most from secondary prevention with A+D.

Data sources: The previously published meta-analysis of individual patient data was updated with data from ESPRIT (n = 2,739); trials without data on the comparison of A+D versus ASA were excluded.

Review methods: A meta-analysis was performed using Cox regression, including several subgroup analyses and following baseline risk stratification.

Results: A total of 7612 patients (five trials) were included in the analyses, 3800 allocated to A+D and 3812 to ASA alone. The trial-adjusted hazard ratio (HR) for the composite event of vascular death, non-fatal myocardial infarction and non-fatal stroke was 0.82 (95% confidence interval (CI) 0.72 to 0.92). HRs did not differ in subgroup analyses based on age, sex, qualifying event, hypertension, diabetes, previous stroke, ischaemic heart disease, aspirin dose, type of vessel disease and dipyridamole formulation, nor across baseline risk strata as assessed with two different risk scores. A+D were also more effective than ASA alone in preventing recurrent stroke; HR 0.78 (95% CI 0.68 to 0.90).

Conclusion: The combination of aspirin and dipyridamole is more effective than aspirin alone in patients with TIA or ischaemic stroke of presumed arterial origin in the secondary prevention of stroke and other vascular events. This superiority was found in all subgroups and was independent of baseline risk.

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  • Competing interests: AA, PMWB, H-CD PHAH and FMY have received grants or honoraria from Boehringer Ingelheim (manufacturer of dipyridamole) and H-CD has received grants or honoraria from Sanofi-Aventis (manufacturer of clopidogrel). Most authors have been involved in the trials included in this analysis: Toulouse (BG-C), ACSSG (FMY), ESPS2 (H-CD), ESPRIT (AA, PHAH, PMWB

  • This study was initiated, analysed, interpreted and funded independently of any pharmaceutical company.