Polypharmacy is differentially associated with 20-year mortality among community-dwelling elderly women and men: The Israel Glucose Intolerance, Obesity and Hypertension cohort study

Background: Elderly individuals are characterized by multimorbidity and high medication intake, entailing risks for adverse events. We examined the overall and sex-specific association of polypharmacy (≥5 drugs concurrently) with 20-year mortality among community-dwelling older adults. Methods: Survivors of the longitudinal Israel Study of Glucose Intolerance, Obesity, and Hypertension underwent extensive evaluation during 1999–2004, and were followed-up for all-cause mortality until 2019. Cox regression examined association of polypharmacy with all-cause mortality. Results: Data included 1210 participants (mean baseline age 72.9 ± 7.4 years, 53% females), 50.7% of them died over a median follow-up of 12.8 years. Women received a higher mean number of drugs (4.3 vs 3.5; p < 0.0001), were twice more likely to take vitamins, and had higher comorbidity. Polypharmacy prevalence was 38.3%, and more frequent with age, female sex, European-American origin, sedentary lifestyle and poor self-rated health. Polypharmacy was independently associated with mortality in women only (HR=1.41, 95%CI:1.05–1.89). An interaction was found with sex (p = 0.045). Conclusions: Polypharmacy was more prevalent in older women than men and associated with increased 20-year mortality in women only. Sex-specific adaptation of guidelines for appropriate drug use among community-dwelling older adults is warranted.