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A Meta-analysis of Randomized Controlled Trials

Jiang He, MD, PhD; Paul K. Whelton, MD, MSc; Brian Vu, BA; Michael J. Klag, MD, MPH

JAMA. 1998;280:1930-1935.

Context.— Aspirin has been widely used to prevent myocardial infarction and ischemic stroke but some studies have suggested it increases risk of hemorrhagic stroke.

Objective.— To estimate the risk of hemorrhagic stroke associated with aspirin treatment.

Data Sources.— Studies were retrieved using MEDLINE (search terms, aspirin, cerebrovascular disorders, and stroke), bibliographies of the articles retrieved, and the authors' reference files.

Study Selection.— All trials published in English-language journals before July 1997 in which participants were randomized to aspirin or a control treatment for at least 1 month and in which the incidence of stroke subtype was reported.

Data Extraction.— Information on country of origin, sample size, duration, study design, aspirin dosage, participant characteristics, and outcomes was abstracted independently by 2 authors who used a standardized protocol.

Data Synthesis.— Data from 16 trials with 55,462 participants and 108 hemorrhagic stroke cases were analyzed. The mean dosage of aspirin was 273 mg/d and mean duration of treatment was 37 months. Aspirin use was associated with an absolute risk reduction in myocardial infarction of 137 events per 10,000 persons (95% confidence interval [CI], 107-167; P<.001) and in ischemic stroke, a reduction of 39 events per 10,000 persons (95% CI, 17-61; P<.001). However, aspirin treatment was also associated with an absolute risk increase in hemorrhagic stroke of 12 events per 10,000 persons (95% CI, 5-20; P<.001). This risk did not differ by participant or study design characteristics.

Conclusions.— These results indicate that aspirin therapy increases the risk of hemorrhagic stroke. However, the overall benefit of aspirin use on myocardial infarction and ischemic stroke may outweigh its adverse effects on risk of hemorrhagic stroke in most populations.

From the Department of Biostatistics and Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, La (Drs He and Whelton); and the Schools of Medicine (Mr Vu and Dr Klag) and Hygiene and Public Health (Dr Klag), Johns Hopkins University, Baltimore, Md.

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