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Background Inflammation is a central pathway leading to frailty but whether commonly used nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can prevent frailty is unknown. Methods Prospective cohort study of male physicians ≥60 who participated in the Physicians’ Health Study. Annual questionnaires collected data on NSAID use, lifestyle, and morbidity. Average annual NSAID use was categorized as 0 days/year, 1–12 days/year, 13–60 days/year, and &amp;gt;60 days/year. Frailty was assessed using a validated 33-item frailty index. Propensity score inverse probability of treatment weighting was used to address confounding by indication and logistic regression models estimated odds ratios (ORs) of prevalent frailty according to nonaspirin NSAID use. Results A total of 12 101 male physicians were included (mean age 70 ± 7 years, mean follow-up 11 years). Reported NSAID use was 0 days/year for 2 234, 1–12 days/year for 5 812, 13–60 days/year for 2 833, and &amp;gt;60 days/year for 1 222 participants. A total of 2 413 participants (20%) were frail. Higher self-reported NSAID use was associated with greater alcohol use, smoking, arthritis, hypertension, and heart disease, while less NSAID use was associated with coumadin use and prior bleeding. After propensity score adjustment, all characteristics were balanced. ORs (95% confidence intervals) of prevalent frailty were 0.90 (0.80–1.02), 1.02 (0.89–1.17), and 1.26 (1.07–1.49) for average NSAID use of 1–12 days/year, 13–60 days/year, and &amp;gt;60 days/year, compared to 0 days/year (p-trend &amp;lt; .001). Conclusions Long-term use of NSAIDs at high frequency is associated with increased risk of frailty among older men. Additional study is needed to understand the role of anti-inflammatory medication in older adults and its implication for overall health.

Influence of Long-term Nonaspirin NSAID Use on Risk of Frailty in Men ≥60 Years: The Physicians’ Health Study