BACKGROUND: Daily aspirin use has been recommended for secondary prevention of cardiovascular disease, but its use for primary prevention remains controversial.

METHODS: We followed 440,277 men and women from the NIH-AARP Diet and Health Study (ages 50-71) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (ages 55-74) for mortality for 13 years on average. Frequency of aspirin use was ascertained through self-report, and cause of death by death certificates. We calculated multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality using Cox proportional hazards models for each cohort and combined by meta-analysis.

RESULTS: We found a consistent U-shaped relationship between aspirin use and mortality in both studies, with differential risk patterns for cardiovascular mortality by disease history. Among individuals with a history of cardiovascular disease, daily aspirin use was associated with reduced cardiovascular mortality [HR = 0.78 (95% CI, 0.74, 0.82)]. However, among those without a previous history, we observed no protection for daily aspirin users [HR = 1.06 (1.02, 1.11)], and elevated risk of cardiovascular mortality for those taking aspirin twice daily or more [HR = 1.29 (1.19, 1.39)]. Elevated risk persisted even among participants who lived beyond 5 years of follow-up and used aspirin without other nonsteroidal antiinflammatory drugs [HR = 1.31 (1.17, 1.47)].

CONCLUSIONS: Results from these 2 large population-based US cohorts confirm the utility of daily aspirin use for secondary prevention of cardiovascular mortality; however, our data suggest that caution should be exercised in more frequent use, particularly among individuals without a history of cardiovascular disease.