Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. 126 | Epidemiology • Volume 29, Number 1, January 2018 O RIGINAL A RTICLE Background: Daily aspirin use has been recommended for second- ary prevention of cardiovascular disease, but its use for primary pre- vention 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 certifi- cates. We calculated multivariate hazard ratios (HRs) and 95% con- fidence 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 aspi- rin 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 pro- tection 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 partici- pants 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 pre- vention 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. ( Epidemiology 2018;29: 126–133) M illions of individuals worldwide take aspirin with approximately 40% of the US population over age 40 years consuming aspirin regularly. 1,2 In randomized controlled trials, daily use of aspirin has been demonstrated to reduce cardiovascular disease incidence and mortality and all-cause mortality among individuals with established cardiovascular disease 3,4 ; however, prophylactic use of aspirin for individuals without a history of cardiovascular disease remains contro- versial. 5 Whereas the American College of Chest Physicians 6 and the US Preventive Services Task Force (USPSTF) 7 sup- port the use of aspirin for primary prevention among select groups, the European Society of Cardiology 8 and the US Food and Drug Administration (FDA) 9 recommend against the use of aspirin for primary prevention of cardiovascular disease, largely due to a lack of mortality benefit and increased risk of major bleeding. Randomized trial data show that daily use of aspirin is associated with a small reduction in cardiovascular incidence but no substantial reduction in cardiovascular mor- tality or all-cause mortality, 10–13 which may be partially due to an increased risk of fatal hemorrhagic stroke.
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