Clinical Question

Does low-dose aspirin reduce all-cause mortality in generally healthy older adults?

Bottom Line

The findings are completely unexpected. Although recent studies by this group and other groups of researchers have failed to find a cardiovascular benefit, likely because of better control of other cardiovascular risk factors, this study found increased all-cause mortality, primarily due to increased cancer-related mortality. Other studies, such as the individual patient meta-analysis by Rothwell and colleagues (Lancet. 2011;377(9759):31–41), found the opposite. A Bayesian thinker would urge caution in interpreting these results, considering the existing body of research concluding the opposite regarding cancer-specific mortality. (Level of Evidence = 1b)

Synopsis

This is one of three reports of the same study in the same issue of the New England Journal of Medicine; this one focuses on all-cause mortality. The Aspirin in Reducing Events in the Elderly trial randomized 19,114 community-dwelling adults to receive 100 mg of enteric-coated aspirin or placebo. The study was conducted in the United States and Australia, with patients recruited between 2010 and 2014. Participants were 70 years or older (65 years or older if black or Hispanic in the United States, because of their shorter average lifespan), had no serious comorbidity that would be expected to limit their life expectancy to less than five years, and no known cardiovascular or cerebrovascular disease, dementia, high bleeding risk, or contraindication to aspirin. The study included a one-month placebo run-in period to ensure at least 80% adherence to the study medication. During the run-in period, 4,049 patients were excluded, 61% because of failed adherence. Included patients were contacted every three months to further encourage adherence and to gather interim data. Outcomes were adjudicated by a committee masked to treatment assignment. The median age of participants was 74 years, 56% were women, and 8.7% were nonwhite. Most of the patients were recruited in Australia (87%), 74% had hypertension, 65% had hyperlipidemia, and only 11% had diabetes mellitus. Participants were followed up for a median of 4.8 years, and only 2.2% withdrew or were lost to follow-up. All-cause mortality was higher in the aspirin group (5.9% vs. 5.2%; hazard ratio [HR] = 1.14; 95% CI, 1.01 to 1.29; number needed to harm [NNH] = 143 over 4.8 years). The likelihood of cancer death was also higher in the aspirin group, with the increased risk beginning after approximately three years of aspirin use (3.1% vs. 2.3%; HR = 1.31; CI, 1.10 to 1.56; NNH = 125 over 4.8 years).

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Population-based

Reference: McNeil JJ, Nelson MR, Woods RL, et al.; ASPREE Investigator Group. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med. 2018;379(16):1519–1528.

Editor's Note: Dr. Ebell is Deputy Editor for Evidence- Based Medicine for AFP and cofounder and Editor-in-Chief of Essential Evidence Plus.