Association of Medication Profiles, Including Polypharmacy, Guideline-Directed Medical Therapy, and Potentially Inappropriate Medications, With All-Cause Mortality in Older Adults With Heart Failure, With or Without Frailty and Disability

BACKGROUND: Polypharmacy, driven by guideline-directed medical therapy (GDMT) and medications for comorbidities, including potentially inappropriate medications (PIMs), is common in older adults with heart failure (HF). Although medication profiles affect survival, the effects of frailty and disability status remain underexplored. METHODS AND RESULTS: This retrospective study assessed polypharmacy (≥5 medications), the use of GDMT, and PIMs based on the Beers Criteria. Frailty and disability status were determined using Japan's Long-term Care Insurance (LTCI) certification. Patients were stratified according to LTCI, and the prognostic impact of medication profiles was analyzed. The total medication count was correlated with both GDMT and PIM use. Among 1,264 patients, those with LTCI were older, had more severe comorbidities, higher polypharmacy and PIM use, and lower use of GDMT medications. In multivariate Cox regression analysis, regardless of LTCI, GDMT medication use was associated with a favorable prognosis (LTCI: odds ratio [OR] 0.47, 95% confidence interval [CI] 0.258-0.866, P=0.015; no LTCI: OR 0.57, 95% CI 0.400-0.799, P=0.001). PIM use was associated with a poor prognosis only in the no-LTCI group (OR 1.51; 95% CI 1.040-2.203; P=0.030). CONCLUSIONS: Polypharmacy may have both beneficial and harmful effects, with prognostic implications potentially influenced by frailty and disability status. Although GDMT medications were consistently associated with favorable outcomes, the impact of PIMs appeared to differ depending on LTCI.