Polypharmacy in Older Adults: The Hazard of Hospitalization and Mortality is Mediated by Potentially Inappropriate Prescriptions, Findings From the Moli-sani Study

Abstract

Objectives: We evaluated the impact of polypharmacy on the health of community-dwelling older adults.

Methods: We prospectively analyzed 5,631 individuals from the Moli-sani study (51% men, aged ≥65 years, recruitment 2005-2010, follow-up 2005-2020). Exposure was categorized as chronic polypharmacy therapy (C-PT; ≥5 therapeutic groups and >2 defined daily doses (DDDs)) or non-chronic polypharmacy therapy (NC-PT; polypharmacy but ≤2 DDDs). Hospitalization and mortality were the main outcomes. The mediating role of potentially inappropriate prescriptions (PIP) was examined.

Results: Compared to individuals not on polypharmacy, those in NC-PT and C-PT had higher hazards of mortality [21% (95% CI 7%-37%) and 30% (16%-46%), respectively] and hospitalization [39% (28%-51%) and 61% (49%-75%), respectively]. Similar results were found for cardiovascular outcomes. PIP mediated the association between polypharmacy and outcomes, with mediation effects ranging from 13.6% for mortality to 6.0% for hospitalization. Older adults without multimorbidity experienced the same harm from multiple medications as those with multimorbidity.

Conclusion: Polypharmacy is associated with a higher hazard of mortality and hospitalization, with PIP playing an important role. Addressing "medication without harm" requires assessing the appropriateness of drug prescriptions and monitoring for adverse effects.

Keywords: elderly; hospitalization; mortality; polypharmacy; potentially inappropriate prescriptions.

FIGURE 1

Multivariable survival estimates for (A) all-cause mortality and (B) all-cause hospitalization according to polypharmacy in the elderly of the Moli-sani study (N = 5,631) (Italy, 2005–2010). Multivariable survival curves were obtained from the multivariable model adjusted for age, sex, education level, income, occupational social class, area of residence, total physical activity, smoking, body mass index, history of cardiovascular disease, general practitioner diagnosis of hypertension, general practitioner diagnosis of type 2 diabetes, atrial fibrillation, heart failure, history of cancer, pulmonary disease, and chronic kidney disease.

FIGURE 2

Role of the potentially inappropriate prescriptions in the relationship between polypharmacy and main outcomes (Moli-sani Study, Italy, 2005–2010). Multivariable survival curves were obtained from the multivariable model adjusted for age, sex, education level, income, occupational social class, area of residence, total physical activity, smoking, body mass index, history of cardiovascular disease, general practitioner diagnosis of hypertension, general practitioner diagnosis of type 2 diabetes, atrial fibrillation, heart failure, history of cancer, pulmonary disease, and chronic kidney disease.