Polypharmacy's Association With Mortality: Confounding From Underlying Morbidity.

Area of Science:

• Gerontology
• Pharmacology
• Epidemiology

Background:

• Studies link polypharmacy (use of multiple medications) to increased mortality.
• Previous research often fails to adequately adjust for confounding factors, especially underlying diseases.

Purpose of the Study:

• To highlight challenges in polypharmacy-mortality research.
• To examine the association between polypharmacy and mortality in two distinct populations: nursing home residents and community-dwelling older adults.

Main Methods:

• Utilized nationwide Danish registers for two cohorts: nursing home admissions (2015-2021, n=95,057) and community-dwelling individuals aged ≥65 (n=1,005,963).
• Assessed 1-year mortality using Kaplan-Meier plots and modeled the polypharmacy-mortality association with restricted cubic splines, applying varying levels of adjustment.
• Investigated associations between the 20 most frequently used drugs and 1-year mortality.

Main Results:

• In nursing home residents, mortality increased with medication count, but adjustment for comorbidities reduced the odds ratio from 4.70 to 2.23.
• In community-dwelling older adults, adjustment had a greater impact, reducing the odds ratio from 10.39 to 1.34.
• Observed paradoxical inverse associations for certain drug classes (e.g., antidementia drugs) and noted medication use fluctuations in nursing home residents but stability in the general population.

Conclusions:

• The association between polypharmacy and mortality is substantially influenced by confounding by indication.
• While comorbidity adjustment attenuates the association, residual confounding may persist.
• Emphasizes the need for careful interpretation of studies linking high medication use to mortality.