Impact of Potentially Inappropriate Medication on Disability and Mortality in Older Adults: Nationwide Population-Based Study in Korea

Background Potentially Inappropriate Medications (PIMs) increase the risk of adverse health outcomes in older adults. However, the long-term effects of PIMs, particularly considering frailty and polypharmacy, remain unclear. Methods We analyzed data from the National Health Insurance Service and the National Screening Program for Transitional Ages (NSPTA) in Korea, including individuals aged 66 who participated between 2015 and 2016. Participants were categorized into PIM and No PIM groups based on prescriptions, with frailty index calculated from NSPTA results. Outcomes were tracked over 6.77 years. The primary outcome was disability; secondary outcomes included all-cause mortality and a composite endpoint of death or disability. The association between PIM and adverse outcomes was evaluated using Cox proportional hazard models. Results A total of 564,036 individuals were included. During follow-up, 10,735 (1.9%) developed disabilities, and 17,887 (3.1%) died. The PIM group (64.4%) showed higher risks of disability (2.3% vs. 1.2%) and mortality (3.6% vs. 2.4%) compared to the No PIM group (P < 0.001). The composite outcome was also more frequent in the PIM group (5.3%) compared to the No PIM group (3.2%) (P < 0.001). PIM use was associated with increased risks of disability (HR 1.22 [95% CI 1.16, 1.28]), mortality (HR 1.15 [95% CI 1.11, 1.19]), and the composite outcome (HR 1.16 [95% CI 1.13, 1.20]), even after adjusting for frailty and polypharmacy. Furthermore, as the number of PIMs increased (0, 1-2, 3-4, ≥5), the risks of disability, mortality, and the composite outcome also significantly increased (all P < 0.001). Conclusion PIM use in older adults raises risk of disability and mortality, even after adjusting to frailty and polypharmacy, and the impact grows with the number of PIMs prescribed.