Updated Meta-Analysis of Aspirin in Primary Prevention of Cardiovascular Disease.

Uncertainty about the balance between risks and benefits of aspirin in the primary prevention of cardiovascular disease is reflected in conflicting recommendations by guideline panels. Our 2011 meta-analysis of 9 randomized controlled trials involving 100,076 patients demonstrated that when used for primary prevention, aspirin prevented all-cause mortality, myocardial infarction, and stroke, but did not prevent cardiovascular mortality, and increased hemorrhagic stroke and major bleeding. The reduction in all-cause mortality was small (6% relative risk reduction) and of borderline statistical significance (P 1⁄4 .05), and in the absence of a reduction in cardiovascular mortality, the relevance of this finding has been challenged. The recently published Japanese Primary Prevention Project (JPPP), an open-label randomized controlled trial comparing aspirin 100 mg once daily with no aspirin in 14,658 participants aged 60 to 85 years with diabetes, hypertension, or hyperlipidemia, has provided additional randomized evidence since 2011. Approximately half of participants in JPPP were over the age of 70 years. Aspirin adherence was 88.9% at 1 year and 76% at 5 years; 9.8% of participants in the nonaspirin arm commenced aspirin during the study, and 10.5% of participants were lost to followup. The study was prematurely terminated for futility at a median of 5.02 years follow-up. The results indicate that aspirin did not prevent all-cause or cardiovascular mortality, but similar to previous studies, prevented nonfatal myocardial infarction at the cost of increased extracranial bleeding and hemorrhagic stroke. Adding the JPPP to our earlier meta-analysis, 10 randomized trials involving a combined total of 114,734 participants have compared aspirin with control for primary prevention of cardiovascular disease. The pooled data