TY - JOUR
T1 - The association between polypharmacy, frailty and disability-free survival in community-dwelling healthy older individuals
AU - Ekram, A. R.M.Saifuddin
AU - Woods, Robyn L.
AU - Ryan, Joanne
AU - Espinoza, Sara E.
AU - Gilmartin-Thomas, Julia F.M.
AU - Shah, Raj C.
AU - Mehta, Raaj
AU - Kochar, Bharati
AU - Lowthian, Judy A.
AU - Lockery, Jessica
AU - Orchard, Suzanne
AU - Nelson, Mark
AU - Fravel, Michelle A.
AU - Liew, Danny
AU - Ernst, Michael E.
N1 - Funding Information:
The ASPREE trial was supported by the National Institute on Aging (NIA) and the National Cancer Institute at the National Institutes of Health (NIH) (grant numbers U01AG029824, U19AG062682); the National Health and Medical Research Council of Australia (NHMRC) (grant numbers 334047, 1127060), Monash University and the Victorian Cancer Agency. In addition, JR is supported by an NHMRC Leader Fellowship (APP1135727). JG-T is supported by an NHMRC-ARC Dementia Research Development Fellowship (APP1107476). The sponsors had no role in the manuscript's design, conduct, drafting, or publication.
Funding Information:
The ASPREE trial was supported by the National Institute on Aging (NIA) and the National Cancer Institute at the National Institutes of Health (NIH) (grant numbers U01AG029824, U19AG062682); the National Health and Medical Research Council of Australia (NHMRC) (grant numbers 334047, 1127060), Monash University and the Victorian Cancer Agency. In addition, JR is supported by an NHMRC Leader Fellowship (APP1135727). JG-T is supported by an NHMRC-ARC Dementia Research Development Fellowship (APP1107476). The sponsors had no role in the manuscript's design, conduct, drafting, or publication. The ASPREE clinical trial is registered with the International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and clinicaltrials.gov (NCT01038583). The ASPREE clinical trial was conducted following the World Medical Association Declaration of Helsinki 1964 as revised in 2008, the NHMRC Guidelines on Human Experimentation, the Federal Patient Privacy (HIPAA) law and the International Conference of harmonisation Guidelines for Good Clinical Practice (ICH-GCP) guidelines and followed the Code of Federal Regulations. It was approved by the Monash University Human Research Ethics Committee (MUHREC) (IRB00002519; ethics #2006/745MC) and other allied institution ethics committees. In addition, the Intellectual Property and Ethics Committee (Reference no. V6VVQTXZ; 29 November 2019) and MUHREC (Ethics #2021/30049) have approved this current project of Monash University. The authors acknowledge the dedicated and skilled staff in Australia and the United States for the trial's conduct. The authors are also most grateful to the ASPREE participants, who willingly volunteered for this study, the general practitioners and the medical clinics that supported the participants in the ASPREE study.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
KW - ASPREE
KW - Disability-free survival
KW - Frailty index
KW - Fried phenotype
KW - Polypharmacy
UR - http://www.scopus.com/inward/record.url?scp=85127022714&partnerID=8YFLogxK
U2 - 10.1016/j.archger.2022.104694
DO - 10.1016/j.archger.2022.104694
M3 - Article
C2 - 35349875
AN - SCOPUS:85127022714
SN - 0167-4943
VL - 101
JO - Archives of Gerontology and Geriatrics
JF - Archives of Gerontology and Geriatrics
M1 - 104694
ER -