No clinical benefit from aspirin for older individuals in primary prevention
Effect of Aspirin on Disability-free Survival in the Healthy Elderly, Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly, Effect of Aspirin on All-Cause Mortality in the Healthy ElderlyLiterature - McNeil JJ, Nelson MR, Woods RL et al. - N Engl J Med 2018; published online ahead of print
Introduction and methods
Aspirin is recommended for the secondary prevention of CV events, but it is not clear, whether it provides benefit in primary prevention, especially in older individuals at higher risk [1-3]. Moreover, there are limited data on the use of aspirin to increase healthy independent life span in this patient group.
In the randomized, double-blind, placebo-controlled Aspirin in Reducing Events in the Elderly (ASPREE) trial [4,5], it was evaluated whether the administration of aspirin 100 mg daily compared with placebo would prolong healthy life span, free from dementia and persistent physical disability in 19,114 healthy, older adults from Australia and the USA
Eligible participants were ≥70 years of age (or ≥65 years of age among blacks and Hispanics), without CV or cerebrovascular disease, or any other chronic disease that would be likely to limit survival to less than 5 years. The composite primary end point of disability-free survival, which was used to reflect a healthy life span, included death from any cause, dementia, and persistent physical disability. Secondary endpoints included CVD (defined as fatal CHD, nonfatal MI, fatal or nonfatal stroke, or hospitalization for HF), cancer-related death, and major bleeding.
The trial was terminated when a futility analysis showed no primary endpoint difference between treatment groups at a median of 4.7 years of follow-up. Event rates were as follows:
- Primary endpoint: 21.5 events per 1,000 person-years in the aspirin group and 21.2 events per 1,000 person-years in the placebo group (HR: 1.01; 95%CI: 0.92-1.11; P=0.79)
- CVD: 10.7 events per 1,000 person-years in the aspirin group and 11.3 events per 1,000 person-years in the placebo group (HR: 0.95; 95%CI: 0.83-1.08)
- Major bleeding: 3.8% in the aspirin group vs. 2.8% in the placebo group, corresponding to 8.6 events per 1,000 person-years and 6.2 events per 1,000 person-years, respectively (HR: 1.38; 95%CI: 1.18-1.62; P<0.001)
- All-cause mortality: 12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group (HR: 1.14; 95%CI: 1.01 to 1.29)
- Cancer-related death: 3.1% of the participants in the aspirin group and in 2.3% of those in the placebo group (HR: 1.31; 95%CI: 1.10-1.56)
Compared with placebo, administration of daily low-dose aspirin to older, healthy adults, did not prolong the 5-year disability-free survival, and was not associated with a lower risk of CVD, but led to higher rates of major bleeding and all-cause mortality, mainly due to cancer-related death.