Aspirin does not reduce composite of death, disability, and dementia in older patients; increases bleeding risk (ASPREE)

Reference

McNeil JJ, Woods RL, Nelson MR, et al, for the ASPREE Investigator Group. Effect of aspirin on disability-free survival in the healthy elderly. N Engl J Med 2018;379(16):1499-1508.

Synopsis

These are the initial results of the landmark Aspirin in Reducing Events in the Elderly (ASPREE) trial. Two other reports describe the effect of aspirin on all-cause mortality and on cardiovascular disease. The authors randomized 19,114 community-dwelling adults to receive either 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 5 years, and no known cardiovascular (CV) or cerebrovascular disease, dementia, high bleeding risk, or contraindication to aspirin. The study included a 1-month placebo run-in period to ensure at least 80% adherence to the study medication. During the run-in period, 4049 patients were excluded, 61% because they failed adherence. Included patients were contacted every 3 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 non-white. Most of the patients were recruited in Australia (87%), 74% had hypertension, 65% had hyperlipidemia, and only 11% had diabetes. Participants were followed up for a median of 4.8 years, and only 2.2% withdrew or were lost to follow-up. The primary outcome was a composite of death, dementia, or physical disability, which occurred in 921 persons who received aspirin and 914 who received placebo (hazard ratio [HR] 1.10; 95% CI 0.92 - 1.11). All-cause mortality was slightly higher in the aspirin group (12.7 vs 11.1 events per 1000 person-years; HR 1.14, 1.01 - 1.29; number needed to treat to harm [NNTH] = 625 per year). Major hemorrhage was more common in the aspirin group (8.6 vs 6.2 events per 1000 person-years; hazard ratio 1.38; 95% CI 1.18 - 1.62; number needed to treat to harm = 417 per year).