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Aspirin use and mortality in two contemporary U.S. cohorts

Huang, Wen-Yi; Daugherty, Sarah E.; Shiels, Meredith S.; Purdue, Mark P.; Freedman, Neal D.; Abnet, Christian C.; Hollenbeck, Albert R.; Hayes, Richard B.; Silverman, Debra T.; Berndt, Sonja I.
doi: 10.1097/EDE.0000000000000746
Original Article: PDF Only


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


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 (CI) for mortality using Cox proportional hazards models for each cohort and combined by meta-analysis.


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 anti-inflammatory drugs [HR=1.31 (1.17-1.47)].


Results from these two large population-based U.S. 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.

Funding Source: The National Institutes of Health AARP Diet and Health Study (NIH-AARP) and Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial are supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), DHHS. PLCO is also supported by contracts from the Division of Cancer Prevention, NCI, NIH, DHHS.

Conflict of Interest Disclosures: none declared.

Acknowledgements: The authors thank the participants from the NIH-AARP and PLCO cohorts for their excellent cooperation in these studies. The authors also thank Mr. Adam Risch and Mr. John Commins, Information Management Services, Inc. for their assistance in the data analysis. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. All statements in this report, including its findings and conclusions, are solely those of the authors and do not necessarily represent the views of the Patient-Centered Outcomes Research Institute (PCORI), its Board of Governors or Methodology Committee.

Data availability: Investigators may apply to access the study data through the National Institutes of Health, AARP Diet and Health Study website ( ) and the PLCO Cancer Data Access System website ( ).

*Correspondence to: Wen-Yi Huang, PhD, MSPH, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive 6E606, Bethesda, MD 20892-9771,, tel: 240-276-7277

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