Introduction: Older people have a high prevalence of polypharmacy and increasingly complex medication regimens. Aims. To investigate whether polypharmacy and medication regimen complexity are associated with all-cause mortality in older people.

Methods: Data were collected as part of the Swedish National Study of Aging and Care Kungsholmen (SNAC-K) study. Polypharmacy was analysed as a continuous variable (number of medications). Medication regimen complexity was assessed using the 65-item Medication Regimen Complexity Index (MRCI) in 10-unit steps. Mortality data were obtained from the Swedish National Cause of Death Register. Cox proportional hazard models were used to compute unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between polypharmacy and regimen complexity with all-cause mortality over a three-year period. Subanalyses were performed stratifying by age (≤80 and >80 years), sex and cognition (Mini-Mental State Examination [MMSE] <26 and ≥26).

Results: Overall, 3348 people aged ≥60 years participated. During follow-up, 14.0% of the participants (n=470) died. After adjusting for age, sex, comorbidity, educational level, activities of daily living, MMSE and living place, polypharmacy was not associated with mortality (adjusted HR=1.03 95% CI 0.99-1.06). In adjusted analyses, higher MRCI was associated with mortality (HR=1.12 95% CI 1.01-1.25). When stratifying by sex, both polypharmacy and MRCI were associated with mortality in men but not in women. MRCI was associated with mortality in participants ≤80 years and participants with MMSE ≥26 but not in participants aged >80 years or with MMSE <26.

Discussion: Regimen complexity was a better overall predictor of mortality than polypharmacy. However, regimen complexity was not predictive of mortality in women, in participants aged >80 years, or those with MMSE <26. These different associations with mortality deserve further investigation.