Polypharmacy and Potentially Inappropriate Medications: Cognitive Consequences in Older Heart Failure Outpatients

Cognitive impairment is prevalent among older heart failure (HF) outpatients. Polypharmacy and potentially inappropriate medications (PIMs) may contribute to cognitive vulnerability, yet evidence using the Beers Criteria 2023 with locally validated cognitive screening in Indonesia remains limited.

A cross-sectional analytic study enrolled 107 consecutive HF outpatients aged 60 years or older at a tertiary teaching hospital in Medan, North Sumatra, Indonesia (August to October 2025). Polypharmacy was categorized as non-polypharmacy, polypharmacy, or hyperpolypharmacy. PIM exposure was classified by Beers Criteria 2023. Cognitive function was assessed by MoCA-INA v7.1. Proportional-odds ordinal logistic regression was used with collinearity assessed by variance inflation factors.

Mean age was 67.6±6.2 years; 59 (55%) were female. Polypharmacy (72%) and hyperpolypharmacy (23%) were prevalent; severe PIM exposure occurred in 39%. Mean MoCA-INA was 22.0±3.3; 78% had mild cognitive impairment and 10% had mild to moderate dementia. Cognitive category correlated with polypharmacy (ρ=0.276; p=0.004) and PIM level (ρ=0.264; p=0.006). All VIFs were below 1.5. In the fully adjusted model, education was independently protective (aOR 0.82 per year; 95% CI 0.68 to 0.99; p=0.04) and HFrEF was associated with worse cognition (aOR 6.10; 95% CI 1.25 to 29.87; p=0.03). Polypharmacy (aOR 2.88; p=0.10) and PIM burden (aOR 1.70; p=0.10) showed directionally consistent but inconclusive adjusted associations (Nagelkerke R²=0.368).

Higher medication burden and Beers-2023 PIM exposure were associated with worse cognitive status in unadjusted analyses; adjusted models showed directionally consistent but statistically inconclusive associations (polypharmacy aOR=2.88, p=0.099; PIM burden aOR=1.70, p=0.098). HFrEF was the most robust independent predictor of worse cognitive status (aOR 6.10; 95% CI 1.25 to 29.87; p=0.03), consistent across all three adjusted models. Education was independently protective. Routine cognitive screening integrated with structured medication review is warranted in HF outpatient care, with particular attention to patients with HFrEF phenotype.