Conflict of interest:
Effect of addition of clopidogrel to aspirin on stroke incidence: Meta-analysis of randomized trials
Article first published online: 22 MAY 2013
© 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization
International Journal of Stroke
Volume 10, Issue 5, pages 686–691, July 2015
How to Cite
Palacio, S., Hart, R. G., Pearce, L. A., Anderson, D. C., Sharma, M., Birnbaum, L. A. and Benavente, O. R. (2015), Effect of addition of clopidogrel to aspirin on stroke incidence: Meta-analysis of randomized trials. International Journal of Stroke, 10: 686–691. doi: 10.1111/ijs.12050
Dr Santiago Palacio declares no conflict of interest.
Dr Robert G. Hart was co-principal investigator of the NIH sponsored SPS 3 trial.
Lesly A. Pearce declares no conflict of interest.
David C. Anderson served as site principal investigator of the NIH sponsored SPS 3 trial.
Dr Mukul Sharma has received honoraria as speaker from BMS/Pfizer and has participated as consultant for BMS/Pfizer.
Lee A. Birnbaum declares no conflict of interest.
Dr Oscar R. Benavente was the principal investigator of the NIH sponsored SPS 3 trial. He has received research support, honoraria and has participated as consultant for Sanofi/BMS.
Funding: None declared.
Disclosures: The author declares no potential conflict of interest.
- Issue published online: 16 JUN 2015
- Article first published online: 22 MAY 2013
- Manuscript Accepted: 31 OCT 2012
- Manuscript Received: 28 AUG 2012
- antiplatelet therapy;
- clinical trials;
It remains controversial whether dual antiplatelet therapy reduces stroke more than aspirin alone.
We aimed to assess the effects of adding clopidogrel to aspirin on the occurrence of stroke and major haemorrhage in patients with vascular disease.
Meta-analysis of published randomized trials comparing the combination of clopidogrel and aspirin vs. aspirin alone that reported stroke and major bleeding.
Thirteen randomized trials were included with a total of 90 433 participants (mean age 63 years; 63% male) with a mean follow-up of 1·0 years and 2011 strokes. Stroke was reduced 19% by dual antiplatelet therapy (odds ratio = 0·81, 95% confidence interval 0·74–0·89) with no evidence of heterogeneity of effect across different trial populations (I2 index = 5%, P = 0·4 for heterogeneity). Dual antiplatelet therapy reduced ischemic stroke by 23% (odds ratio = 0·77; 95% confidence interval 0·70–0·85); there was a nonsignificant 12% increase in intracerebral haemorrhage (odds ratio = 1·12, 95% confidence interval 0·86–1·46). Among 1930 participants with recent (<30 days) brain ischemia from four trials, stroke was reduced by 33% (odds ratio = 0·67, 95% confidence interval 0·46–0·97) by dual antiplatelet therapy vs. aspirin alone. The risk of major bleeding was increased by 40% (odds ratio = 1·40, 95% confidence interval 1·26–1·55) by dual antiplatelet therapy.
This meta-analysis demonstrates a substantial relative risk reduction in stroke by clopidogrel plus aspirin vs. aspirin alone that is consistent across different trial cohorts. Major haemorrhage is increased by dual antiplatelet therapy.