Low-dose aspirin did not reduce fracture risks in healthy older adults, but was associated with an increased risk of serious falls, a substudy of the ASPREE randomized trial showed.
During a median follow-up of 4.6 years, there was no difference in the risk of a first fracture between participants taking aspirin 100 mg daily and those taking placebo (HR 0.97, 95% CI 0.87-1 .06, P=0.50), but aspirin was associated with an increased risk of serious falls (incidence rate ratio 1.17, 95% CI 1.03-1.33, P=0.01), reported Anna L. Barker, PhD, of Monash University in Melbourne, Australia, and coauthors.
The results did not change after adjusting for covariates known to influence the risk of fractures and falls, they noted in JAMA Internal Medicine.
“This finding adds to evidence from the main ASPREE trial which showed that, among these participants, the use of low-dose aspirin conferred no advantage in terms of disability-free survival (a compound that integrated the risks and benefits of aspirin) ,” they wrote.
“The increase in serious falls observed among those randomized to aspirin was not anticipated and could have been the result of a greater propensity to fall or more significant injuries without fractures sustained as a result of falls,” they noted. “It was originally hypothesized that aspirin might decrease falls by slowing physical decline by reducing cardiovascular and cerebrovascular events through antiplatelet effects and/or reducing cognitive decline by protecting against Alzheimer’s disease and/or Alzheimer’s disease. vascular dementia, well-known risk factors for falls”.
Falls account for 95% of hip fractures and about 80% of traumatic brain injuryHospital presentations and deaths in older adults related to the disease, Barker and co-authors said, adding that “the burden of falls and fractures is likely to increase with population aging, as the risks of falls and fractures increase exponentially with age.
One reason for the lack of reduction in fall risks seen in the treatment group might be related to aspirin’s similar lack of protective effect against cognitive decline, they suggested, noting that recent findings from another analysis of ASPREE, which showed that daily low-dose aspirin did not reduce the risks of dementia, mild cognitive impairment, or cognitive decline.
For the ASPREE-FRACTURE substudy, Barker’s group recruited 16,703 older adults living in the community without cardiovascular disease, dementia, or physical disability between 2010 and 2014. The median age was 74 years and 55% were women.
Of these participants, 8,322 were randomized to aspirin and 8,381 to placebo. During follow-up, 2,865 fractures were recorded, as well as 1,688 serious falls (884 in the aspirin arm vs. 804 in the placebo arm).
To enhance the generalizability of the substudy and avoid fracture misclassification, Barker and colleagues included non-osteoporotic fractures in this analysis. While aspirin use is thought to help reduce bone fragility and falls by slowing bone loss, the authors pointed to a review of the literature suggesting that a 17% reduction in fracture odds seen with aspirin use aspirin was only marginally associated with bone mineral density. Also, most fractures occur in people without bone lossthey pointed out
Limitations of the study included the inability to generalize the findings to less healthy and higher-risk populations, the authors said, as well as the fact that the duration and dose of treatment may have been insufficient to allow for a full effect.
However, the results are clinically relevant “for the large percentage of the older population who are at risk of fracture and take aspirin for the prevention of cardiovascular and cerebrovascular disease,” they concluded. “The lack of an effect of low-dose aspirin on fracture risk while increasing the risk of serious falls adds to the body of evidence that this agent provides unfavorable benefit in a population of healthy older white adults.”
This study was supported by the National Institute on Aging, the National Cancer Institute, the National Health and Medical Research Council of Australia, Monash University and the Cancer Agency of Victoria. Bayer provided the test drug and placebo but had no other role in this trial. ASPREE was also supported by the Claude D. Pepper Center for Independence of Older Americans at the University of Pittsburgh and the Claude D. Pepper Center for Independence of Older Americans at Wake Forest University.
Barker and several co-authors reported support from the Australian National Health and Medical Research Council. Other coauthors reported relationships with Amgen, Alexion, and Sanofi.