Dr. Le
Clinical question: Does daily low-dose aspirin for primary prevention decrease fractures and fall-related hospital presentations in healthy older adults?
Background: Falls and resulting fractures contribute significantly to the burden of disease in the elderly. Aspirin may reduce bone fragility and falls by delaying bone loss, but no randomized controlled trials have previously investigated this.
Study design: Double-blind, randomized, placebo-controlled, primary-prevention trial; outcome analyses on an intention-to-treat basis.
Setting: Elderly adults living in the community recruited by general practice clinics in Australia as part of the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial.
Synopsis: The ASPREE-FRACTURE sub-study included 16,703 healthy, community-dwelling adults older than 69 years without significant cognitive impairment, who were randomized 1:1 to receive 100 mg enteric-coated aspirin or placebo daily, seen in person annually, and followed by telephone every 3 to 6 months for a median of 4.6 years. No difference was seen in first (HR, 0.97; 95% CI, 0.87-1.06; P=0.50) or recurrent (HR, 0.96; 95% CI, 0.87-1.06; P=0.40) fracture events. However, aspirin was associated with a higher risk of serious falls (884 versus 804, incidence rate ratio 1.17; 95% CI, 1.03-1.33; P=0.01). Results were unchanged when adjusted for covariates that influence fracture and fall risk.
Limitations include a lack of generalizability with an older, relatively healthy cohort. The intervention duration and aspirin dose may not be enough to allow for changes that affect fracture risk. Bone quality markers and comorbidities, like inflammatory arthritis and osteoporosis, that affect study risks were not measured.
This sub-study supports the findings of the ASPREE principal trial that the use of low-dose aspirin did not prolong disability-free survival.
Bottom line: Daily low-dose aspirin use in healthy older adults increases serious fall risk but does not affect fracture risk.
Citation: Barker AL, et al. Daily low-dose aspirin and risk of serious falls and fractures in healthy older people. A substudy of the ASPREE randomized clinical trial. JAMA Intern Med. 2022;182(12):1289-97.
Dr. Le is an academic hospitalist at Richmond Veterans Affairs Medical Center, and an assistant professor of medicine at Virginia Commonwealth University in Richmond, Va.
The claim that low-dose aspirin use in healthy older adults elevates the risk of serious falls is clinically misleading and lacks meaningful statistical support. Despite a p-value < 0.05, the fragility index was 5 with a fragility quotient (FQ) of 0.0003. Although defining specific thresholds for fragility is not universally agreed upon, there is broad consensus that a FQ of 0.0003 signifies highly fragile data. Clinical practice should not be changed based on such unreliable statistical findings. Reference: M.V.F. Garcia, J.C. Ferreira and P. Caruso (2023) Fragility index and fragility quotient in randomized clinical trials. Jornal Brasileiro de Pneumologia. [doi]:10.36416/1806-3756/e20230034 {PMID}:36946820 PMCID:PMC10171299)