Background/Purpose: Acetaminophen is widely recommended for osteoarthritis (OA) pain management due to its perceived safety profile. However, its long-term effects on clinical outcomes among older adults remain poorly defined. This study aimed to assess the association between acetaminophen use and mortality, cardiovascular, gastrointestinal, and laboratory outcomes in a large OA population.

Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults aged ≥65 years with osteoarthritis were identified between January 1, 2004, and December 31, 2024. Cohort 1 (n=1,090,625) included patients who initiated acetaminophen within one year of OA diagnosis; Cohort 2 (n=2,174,179) included patients with OA who did not receive acetaminophen. After 1:1 propensity score matching for demographics, comorbidities, and medications, 483,647 patients per cohort were analyzed. Outcomes over three years included death, peptic ulcer disease (PUD), lower gastrointestinal bleeding (LGIB), myocardial infarction (MI), stroke, and laboratory measures of creatinine and hemoglobin. Comparative analyses included measures of association and Kaplan-Meier survival.

Results: Post-matching, baseline characteristics were balanced. Acetaminophen use was associated with increased risks of death (HR 1.46, 95% CI 1.43–1.48, p< 0.001), PUD (HR 3.11, 95% CI 2.91–3.32, p< 0.001), LGIB (HR 1.98, 95% CI 1.91–2.05, p< 0.001), MI (HR 2.12, 95% CI 2.05–2.19, p< 0.001), and stroke (HR 1.70, 95% CI 1.65–1.75, p< 0.001). Survival probability at three years was lower in acetaminophen users compared to non-users (89.7% vs 92.7%). Laboratory analysis revealed higher mean creatinine (1.07 vs 1.00 mg/dL, p< 0.001) and lower mean hemoglobin (12.39 vs 13.29 g/dL, p< 0.001) among acetaminophen users.

Conclusion: In a large cohort of older adults with OA, acetaminophen use was associated with significantly increased risks of mortality, gastrointestinal bleeding, cardiovascular events, and laboratory abnormalities compared to non-use. These findings challenge the notion of acetaminophen as a universally benign analgesic in older patients with OA and highlight the need for more cautious prescribing practices and patient monitoring.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-acetaminophen-use-with-clinical-outcomes-in-older-adults-with-osteoarthritis-a-global-propensity-matched-retrospective-cohort-analysis/