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January/February 2024
Fall Risk: Daily Aspirin and Fall Risk Research Indicates That Daily Low-Dose Aspirin Use Increases Fall Risk For adults 65 years of age and older, falls are the leading cause of both fatal and nonfatal injuries. Annually, one in four older adults report falling, according to the CDC. Most falls are preventable. But an often-overlooked factor for increased fall risk is the use of over-the-counter (OTC) medications, including NSAIDs such as aspirin, ibuprofen, and naproxen. It’s often assumed that OTC drugs are safe, with few side effects. But that’s often not the case, especially for older adults. Daily low-dose aspirin (100 mg or fewer) has previously been recommended for primary prevention of cardiovascular disease in younger adults; the US Preventive Services Task Force now recommends against low-dose aspirin use in adults aged 60 years and older (See sidebar). However, a recent study reported that almost 10 million Americans aged 70 years and older—about half of the US older adult population—continue to take daily aspirin for primary prevention.1 Many older adults may “mix and match” that daily aspirin with another NSAID or take a higher dose of aspirin for relief from chronic pain. Aspirin and Fall Risk The Aspirin in Reducing Events in the Elderly clinical trial was a randomized, double-blind trial that evaluated whether daily low-dose (100 mg) enteric-coated aspirin taken for five years reduced dementia, disability, and death in approximately 20,000 relatively healthy community-dwelling adults aged 70 years and older in primary care practices across Australia and the United States. Eligible participants did not have cardiovascular disease, dementia, or physical disability, or a contraindication to, or indication for, aspirin. Participants were randomized to receive either daily aspirin or an identical enteric-coated placebo tablet. The majority of study participants were white and reported no difficulties with walking or activities of daily living like bathing. The most common health conditions reported were hypertension (75%) and osteoarthritis (56.3%). Approximately 63% of participants self-rated their health as excellent or very good, 32% rated it as good, and 4% rated it as fair/poor.2,3 The ASPREE-FRACTURE substudy analyzed 16,703 Australian older adults who participated in the larger trial and were recruited between 2010 and 2014; 8,322 participants took daily low-dose aspirin and 8,381 participants took the placebo. The goal of the substudy was to determine if daily aspirin use increased risk of fractures in older adults.3 ASPREE-FRACTURE researchers analyzed the occurrence of any fracture as the primary outcome and any serious fall resulting in a hospital visit as a secondary outcome. Study participants were followed for a median of 4.6 years, during which 2,865 fractures and 1,688 serious falls occurred. Aspirin use was not associated with fracture risk—researchers found no difference between those taking aspirin and those taking placebo regarding occurrence of fractures. However, aspirin was linked to a greater risk of serious falls—participants taking aspirin experienced a statistically significantly greater number of serious falls (884 vs 804; P = 0.01).3 “Those receiving aspirin experienced a greater number of serious falls, either single or multiple, which required hospital presentation, with or without accompanying fractures,” Barker and colleagues wrote. Further analysis indicated that fall risk associated with aspirin use was greatest for underweight older adults and those who considered their health status as fair or poor. The researchers note that the increase in serious falls among those randomized to aspirin was unanticipated. “It was originally hypothesized that aspirin may 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 vascular dementia—well-known fall risk factors,” Barker and colleagues note. The study did not specifically analyze potential mechanisms for the aspirin-associated increased fall risk; analyses of factors known to influence fall risk did not identify any variables that contributed to increased fall risk. The researchers speculate that aspirin-induced side effects, such as anemia, might have contributed.3 Based on their analysis, Barker and her colleagues conclude, “the lack of an effect of low-dose aspirin on the risk of fractures while increasing the risk of serious falls adds to the body of evidence that this agent provides little favorable benefit in a healthy, white older adult population.”3 The ASPREE-FRACTURE substudy is the first analysis of randomized placebo-controlled trial data on the effect of aspirin administration on incident fractures and falls. Its results add to the evidence that daily low-dose aspirin use is not as beneficial for older adults without cardiovascular disease as previously thought. The main ASPREE trial found that daily aspirin use did not prolong disability-free survival and, in fact, was linked to a higher rate of major bleeding episodes.4 Another analysis of the ASPREE data demonstrated that daily low-dose aspirin also did not reduce mild cognitive impairment, cognitive decline, or dementia risk.5 Research into NSAIDs, including aspirin, and their impact on fall risk has been limited, despite their common and widespread use among older adults.6 Other pain medications, such as opioids and muscle relaxants, as well as polypharmacy, have been more thoroughly researched. Earlier research into fall risk and NSAID use in older adults found an increased risk of falls, so the lack of research relative to other pain medications is surprising. A 2009 systematic review including 13 studies that evaluated NSAIDs and fall risk found that all studies demonstrated an increased fall risk associated with NSAID use in older adults. Higher quality studies included in the review suggested that community-dwelling elderly adults using NSAIDs had a higher risk of falling.7 A 2015 review of 16 studies also found that older adults using NSAIDs experienced a higher rate of falls than that of those not taking NSAIDs regularly.6 A 2023 population-based study using a health care claims database investigated the link between 32 medications and fall-related injuries in older adults. NSAIDs were found to increase fall risk and fall-related injuries, along with other medications such as opioids, antiepileptics, antipsychotics, antidepressants, hypnotics and sedatives, and muscle relaxants.8 However, none of these studies reported results related to fall risk for aspirin separately. Aspirin and other OTC NSAID use may fall under the radar when geriatric patients report medication use and when the risks associated with polypharmacy are being assessed by care providers. Given the results of the ASPREE-FRACTURE study, a closer look at daily low-dose aspirin use in older adults without cardiovascular disease is warranted. — J.E. Whilldin is a medical research analyst and writer from the Reading, Pennsylvania, area.
References 2. McNeil JJ, Woods RL, Nelson MR, et al. Baseline characteristics of participants in the ASPREE (ASPirin in Reducing Events in the Elderly) study. J Gerontol A Biol Sci Med Sci. 2017;72(11):1586-1593. Erratum in: J Gerontol A Biol Sci Med Sci. 2019;74(5):748. 3.Barker AL, Morello R, Thao LTP, 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):1289-1297. 4. McNeil JJ, Woods RL, Nelson MR, et al. Effect of aspirin on disability-free survival in the healthy elderly. N Engl J Med. 2018;379(16):1499-1508. 5. Ryan J, Storey E, Murray AM, et al. Randomized placebo-controlled trial of the effects of aspirin on dementia and cognitive decline. Neurology. 2020;95(3):e320-e331. 6. Findley LR, Bulloch MN. Relationship between nonsteroidal anti-inflammatory drugs and fall risk in older adults. Consult Pharm. 2015;30(6):346-351. 7. Hegeman J, van den Bemt BJ, Duysens J, van Limbeek J. NSAIDs and the risk of accidental falls in the elderly: a systematic review. Drug Saf. 2009;32(6):489-498. 8. Jung YS, Suh D, Kim E, Park HD, Suh DC, Jung SY. Medications influencing the risk of fall-related injuries in older adults: case-control and case-crossover design studies. BMC Geriatr. 2023;23(1):452.
Low-Dose Aspirin In 2016, the US Preventive Services Task Force (USPSTF) recommended low-dose aspirin for the primary prevention of cardiovascular disease and colorectal cancer in adults aged 50 to 59 years with a 10% or greater risk of developing cardiovascular disease in 10 years and no increased risk of bleeding. For adults aged 60 to 69 years with the same risk level, the USPSTF recommended that the decision to use low-dose aspirin for primary prevention should be made based on individual communication with their physicians. In 2022, after an analysis of updated published evidence, the USPSTF changed its recommendations on low-dose aspirin use. Now, for adults aged 40 to 59 years, the USPSTF recommends that the decision to use low-dose aspirin for primary prevention in those with a 10% or greater risk of developing cardiovascular disease should be made based on discussions between patients and their physicians. For adults aged 60 years and older, the USPSTF recommends against beginning low-dose aspirin use for the primary prevention of cardiovascular disease. It also concluded that evidence is insufficient to support aspirin use for reducing colorectal cancer incidence or mortality. — Source: Aspirin use to prevent cardiovascular disease: preventive medication. US Preventive Services Task Force website. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/aspirin-to-prevent-cardiovascular-disease-preventive-medication. Published April 26, 2022. |
