Santiago Palacio1, Robert G Hart2, Lesly A Pearce3, David C Anderson4, Mukul Sharma2, Lee A Birnbaum1, Oscar R Benavente5. 1. Department of Neurology, University of Texas Health Science Center, San Antonio, TX, USA. 2. Department of Medicine (Neurology), McMaster University, Hamilton, ON, Canada. 3. Biostatistical Consultant, Minot, ND, USA. 4. Department of Neurology, University of Minnesota, Minneapolis, MN, USA. 5. Department of Medicine (Neurology), Brain Research Center, University of British Columbia, Vancouver, BC, Canada.
Abstract
BACKGROUND: It remains controversial whether dual antiplatelet therapy reduces stroke more than aspirin alone. AIM: We aimed to assess the effects of adding clopidogrel to aspirin on the occurrence of stroke and major haemorrhage in patients with vascular disease. METHODS: Meta-analysis of published randomized trials comparing the combination of clopidogrel and aspirin vs. aspirin alone that reported stroke and major bleeding. RESULTS: 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 (I(2) 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. CONCLUSIONS: 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.
BACKGROUND: It remains controversial whether dual antiplatelet therapy reduces stroke more than aspirin alone. AIM: We aimed to assess the effects of adding clopidogrel to aspirin on the occurrence of stroke and major haemorrhage in patients with vascular disease. METHODS: Meta-analysis of published randomized trials comparing the combination of clopidogrel and aspirin vs. aspirin alone that reported stroke and major bleeding. RESULTS: 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 (I(2) 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. CONCLUSIONS: 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.
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