Polypharmacy and Incident Frailty in a Longitudinal Community-Based Cohort Study

OBJECTIVES Polypharmacy may affect frailty, a common and costly condition among older adults. Frailty prevalence is elevated among racial/ethnic minorities and persons living in the US South, and research is needed to inform future pharmacologic interventions in these populations. Our aim was to quantify the prevalence of frailty and polypharmacy, and to estimate the association between polypharmacy and incident frailty. DESIGN Prospective cohort study. SETTING A community-based cohort study of adults residing in Johnston County, North Carolina. PARTICIPANTS White and African American adults aged 50 to 95 years (n=1697). MEASUREMENTS At each study visit, all prescription and over-the-counter medications were recorded. We calculated annual polypharmacy (5-9 medications) and excessive polypharmacy (>= 10 medications) prevalence at the 2006-2010 visit (n = 1697) and operationalized the Fried frailty phenotype to describe prevalent and incident frailty at two consecutive visits (2006-2010 and 2013-2015). We estimated risk ratios (RRs) and 95% confidence intervals (CIs) for the association between polypharmacy and incident frailty using weighted log-binomial regression to account for measured confounding and attrition using inverse probability of treatment and attrition weights, respectively. RESULTS At the 2006-2010 visit, 678 (41%) and 260 (16%) participants were exposed to polypharmacy and excessive polypharmacy, respectively. Overall, 353 (21%) participants and 180 (21%) participants were frail at the 2006-2010 and 2013-2015 visits, respectively. Frailty was more common among participants identifying as white, women, and having less educational attainment relative to those without these characteristics. Incident frailty at the 2013-2015 visit was 15% (mean follow-up = 5.5 years). Our results suggest that polypharmacy is positively associated with incident frailty (weighted RR = 1.4; 95% CI = .9-2.0), yet estimates are imprecise and should be interpreted with caution. CONCLUSION Consistent with the current weight of evidence, our results suggest an association between polypharmacy and incident frailty. Prospective studies evaluating deprescribing interventions are needed to clarify whether reducing polypharmacy decreases frailty incidence.