Polypharmacy Is Associated With Higher Frailty Risk in Older People: An 8-Year Longitudinal Cohort Study

Objective: To investigate whether polypharmacy is associated with a higher incidence of frailty in a large cohort of North Americans during 8 years of follow-up.

Design: Longitudinal study, follow-up of 8 years.

Participants: A total of 4402 individuals at high risk or having knee osteoarthritis free from frailty at baseline.

Measurements: Details regarding medication prescription were captured and categorized as 0-3, 4-6, and ≥7. Frailty was defined using the Study of Osteoporotic Fracture index as the presence of ≥2 out of (1) weight loss ≥5% between baseline and the subsequent follow-up visit; (2) inability to do 5 chair stands; and (3) low energy level according to the Study of Osteoporotic Fracture definition. Cox's regression models calculating a hazard ratio (HR) with 95% confidence intervals (CIs), adjusted for potential confounders, were undertaken.

Results: During the 8-year follow-up, from 4402 participants at baseline, 361 became frail. Compared with participants taking 0-3 medications, the incidence of frailty was approximately double in those taking 4-6 medications and 6 times higher in people taking ≥7 medications. After adjusting for 11 potential baseline confounders, participants using 4-6 medications had a higher risk of frailty of 55% (HR = 1.55; 95% CI 1.22-1.96; P < .0001), whereas those using more than 7 drugs were at approximately 147% (HR = 2.47; 95% CI 1.78-3.43; P < .0001). Each additional drug used at the baseline increased the risk of frailty at the follow-up of 11% (HR = 1.11; 95% CI 1.07-1.15; P < .0001).

Conclusions: Polypharmacy is associated with a higher incidence of frailty over 8-year follow-up period. Our data suggest evidence of a dose response relationship. Future research is required to confirm our findings and explore underlying mechanisms.