The association between polypharmacy, frailty and disability-free survival in community-dwelling healthy older individuals

A. R.M.Saifuddin Ekram, Robyn L. Woods, Joanne Ryan, Sara E. Espinoza, Julia F.M. Gilmartin-Thomas, Raj C. Shah, Raaj Mehta, Bharati Kochar, Judy A. Lowthian, Jessica Lockery, Suzanne Orchard, Mark Nelson, Michelle A. Fravel, Danny Liew, Michael E. Ernst

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9 Citations (Scopus)


Objectives: Polypharmacy and frailty are two common geriatric conditions. In community-dwelling healthy older adults, we examined whether polypharmacy is associated with frailty and affects disability-free survival (DFS), assessed as a composite of death, dementia, or persistent physical disability. Methods: We included 19,114 participants (median age 74.0 years, IQR: 6.1 years) from ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial. Frailty was assessed by a modified Fried phenotype and a deficit accumulation Frailty Index (FI). Polypharmacy was defined as concomitant use of five or more prescription medications. Multinomial logistic regression was used to examine the cross-sectional association between polypharmacy and frailty at base line, and Cox regression to determine the effect of polypharmacy and frailty on DFS over five years. Results: Individuals with polypharmacy (vs. <5 medications) were 55% more likely to be pre-frail (Relative Risk Ratio or RRR: 1.55; 95%Confidence Interval or CI:1.44, 1.68) and three times more likely to be frail (RRR: 3.34; 95%CI:2.64, 4.22) according to Fried phenotype. Frailty alone was associated with double risk of the composite outcome (Hazard ratio or HR: 2.16; 95%CI: 1.56, 2.99), but frail individuals using polypharmacy had a four-fold risk (HR: 4.24; 95%CI: 3.28, 5.47). Effect sizes were larger when frailty was assessed using the FI. Conclusion: Polypharmacy was significantly associated with pre-frailty and frailty at baseline. Polypharmacy-exposed frailty increased the risk of reducing disability-free survival among older adults. Addressing polypharmacy in older people could ameliorate the impact of frailty on individuals’ functional status, cognition and survival.

Original languageEnglish
Article number104694
Number of pages9
JournalArchives of Gerontology and Geriatrics
Publication statusPublished - Jul 2022


  • Disability-free survival
  • Frailty index
  • Fried phenotype
  • Polypharmacy

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