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

      Abstract

      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.

      Keywords

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      References

        • Clegg A.
        • Young J.
        • Iliffe S.
        • et al.
        Frailty in elderly people.
        Lancet (London, England). 2013; 381: 752-762
        • Veronese N.
        • Cereda E.
        • Stubbs B.
        • et al.
        Risk of cardiovascular disease morbidity and mortality in frail and pre-frail older adults: Results from a meta-analysis and exploratory meta-regression analysis.
        Ageing Res Rev. 2017; 35: 63-73
        • Veronese N.
        • Stubbs B.
        • Fontana L.
        • et al.
        Frailty is associated with an increased risk of incident type 2 diabetes in the elderly.
        JAm Med Dir Assoc. 2016; 17: 902-907
        • Herr M.
        • Robine J.M.
        • Pinot J.
        • et al.
        Polypharmacy and frailty: Prevalence, relationship, and impact on mortality in a French sample of 2350 old people.
        Pharmacoepidemiol Drug Saf. 2015; 24: 637-646
        • Chang C.I.
        • Chan D.C.
        • Kuo K.N.
        • et al.
        Prevalence and correlates of geriatric frailty in a northern Taiwan community.
        J Formos Med Assoc. 2011; 110: 247-257
        • Gnjidic D.
        • Hilmer S.N.
        • Blyth F.M.
        • et al.
        High-risk prescribing and incidence of frailty among older community-dwelling men.
        Clin Pharmacol Ther. 2012; 91: 521-528
        • Jamsen K.M.
        • Bell J.S.
        • Hilmer S.N.
        • et al.
        Effects of changes in number of medications and drug burden index exposure on transitions between frailty states and death: The Concord Health and Ageing in Men Project Cohort Study.
        J Am Geriatr Soc. 2016; 64: 89-95
        • Saum K.U.
        • Schottker B.
        • Meid A.D.
        • et al.
        Is polypharmacy associated with frailty in older People? Results from the ESTHER cohort study.
        J Am Geriatr Soc. 2016; 65: e27-e32
        • Pilotto A.
        • Gallina P.
        • Copetti M.
        • et al.
        Warfarin treatment and all-cause mortality in community-dwelling older adults with atrial fibrillation: A retrospective observational study.
        J Am Geriatr Soc. 2016; 64: 1416-1424
        • Pilotto A.
        • Gallina P.
        • Panza F.
        • et al.
        Relation of statin use and mortality in community-dwelling frail older patients with coronary artery disease.
        Am J Cardiol. 2016; 118: 1624-1630
        • Tinetti M.E.
        • McAvay G.
        • Trentalange M.
        • et al.
        Association between guideline recommended drugs and death in older adults with multiple chronic conditions: Population-based cohort study.
        BMJ. 2015; 351: h4984
        • Jha S.R.
        • Hannu M.K.
        • Wilhelm K.
        • et al.
        Reversibility of frailty in advanced heart failure patients listed for transplantation.
        J Heart Lung Transplant. 2016; 35: S29
        • Viktil K.K.
        • Blix H.S.
        • Moger T.A.
        • Reikvam A.
        Polypharmacy as commonly defined is an indicator of limited value in the assessment of drug-related problems.
        Br J Clin Pharmacol. 2007; 63: 187-195
        • Pilotto A.
        • Ferrucci L.
        • Franceschi M.
        • et al.
        Development and validation of a multidimensional prognostic index for one-year mortality from comprehensive geriatric assessment in hospitalized older patients.
        Rejuvenation Res. 2008; 11: 151-161
        • Ensrud K.E.
        • Ewing S.K.
        • Taylor B.C.
        • et al.
        Frailty and risk of falls, fracture, and mortality in older women: The study of osteoporotic fractures.
        J Gerontol Ser A Biol Sci Med Sci. 2007; 62: 744-751
        • Misra D.
        • Felson D.T.
        • Silliman R.A.
        • et al.
        Knee osteoarthritis and frailty: Findings from the Multicenter Osteoarthritis Study and Osteoarthritis Initiative.
        J Gerontol Ser A Biol Sci Med Sci. 2015; 70: 339-344
        • Washburn R.A.
        • McAuley E.
        • Katula J.
        • et al.
        The physical activity scale for the elderly (PASE): Evidence for validity.
        J Clin Epidemiol. 1999; 52: 643-651
        • Katz J.N.
        • Chang L.C.
        • Sangha O.
        • et al.
        Can comorbidity be measured by questionnaire rather than medical record review?.
        Med Care. 1996; 34: 73-84
        • Artaza-Artabe I.
        • Sáez-López P.
        • Sánchez-Hernández N.
        • et al.
        The relationship between nutrition and frailty: Effects of protein intake, nutritional supplementation, vitamin D and exercise on muscle metabolism in the elderly. A systematic review.
        Maturitas. 2016; 93: 89-99
        • Veronese N.
        • Stubbs B.
        • Noale M.
        • et al.
        Adherence to the Mediterranean diet is associated with better quality of life: Data from the Osteoarthritis Initiative.
        Am J Clin Nutr. 2016; 104: 1403-1409
        • Veronese N.
        • Stubbs B.
        • Noale M.
        • et al.
        Adherence to a Mediterranean diet is associated with lower prevalence of osteoarthritis: Data from the osteoarthritis initiative.
        Clin Nutr. 2016 Oct 8; ([Epub ahead of print])
        • Grambsch P.M.
        • Therneau T.M.
        Proportional hazards tests and diagnostics based on weighted residuals.
        Biometrika. 1994; 81: 515-526
        • Chan R.
        • Leung J.
        • Woo J.
        Dietary patterns and risk of frailty in Chinese community-dwelling older people in Hong Kong: A prospective cohort study.
        Nutrients. 2015; 7: 7070-7084
        • León-Muñoz L.M.
        • Guallar-Castillón P.
        • López-García E.
        • Rodríguez-Artalejo F.
        Mediterranean diet and risk of frailty in community-dwelling older adults.
        J Am Med Dir Assoc. 2014; 15: 899-903
        • Talegawkar S.A.
        • Bandinelli S.
        • Bandeen-Roche K.
        • et al.
        A higher adherence to a Mediterranean-style diet is inversely associated with the development of frailty in community-dwelling elderly men and women.
        J Nutr. 2012; 142: 2161-2166
        • Soysal P.
        • Isik A.T.
        • Stubbs B.
        • et al.
        Acetylcholinesterase inhibitors are associated with weight loss in older people with dementia: A systematic review and meta-analysis.
        J Neurol Neurosurg Psychiatry. 2016; 87: 1368-1374
        • Agostini J.V.
        • Han L.
        • Tinetti M.E.
        The relationship between number of medications and weight loss or impaired balance in older adults.
        J Am Geriatr Soc. 2004; 52: 1719-1723
        • Guthrie B.
        • McCowan C.
        • Davey P.
        • et al.
        High risk prescribing in primary care patients particularly vulnerable to adverse drug events: Cross-sectional population database analysis in Scottish general practice.
        BMJ. 2011; 342: d3514
        • Lyles A.
        • Culver N.
        • Ivester J.
        • Potter T.
        Effects of health literacy and polypharmacy on medication adherence.
        Consult Pharm. 2013; 28: 793-799
        • Leendertse A.J.
        • Egberts A.C.
        • Stoker L.J.
        • van den Bemt P.M.
        Frequency of and risk factors for preventable medication-related hospital admissions in The Netherlands.
        Arch Intern Med. 2008; 168: 1890-1896
        • Bourgeois F.T.
        • Shannon M.W.
        • Valim C.
        • Mandl K.D.
        Adverse drug events in the outpatient setting: An 11-year national analysis.
        Pharmacoepidemiol Drug Saf. 2010; 19: 901-910
        • Mangoni A.A.
        Predicting and detecting adverse drug reactions in old age: Challenges and opportunities.
        Expert Opin Drug Metab Toxicol. 2012; 8: 527-530
        • Maher R.L.
        • Hanlon J.
        • Hajjar E.R.
        Clinical consequences of polypharmacy in elderly.
        Expert Opin Drug Saf. 2014; 13: 57-65
        • Pilotto A.
        • Cella A.
        • Pilotto A.
        • et al.
        Three decades of comprehensive geriatric assessment: Evidence coming from different healthcare settings and specific clinical conditions.
        J Am Med Dir Assoc. 2017; 18: 192.e1-192.e11
        • Pilotto A.
        • Sancarlo D.
        • Daragjati J.
        • Panza F.
        Perspective: The challenge of clinical decision-making for drug treatment in older people. The role of multidimensional assessment and prognosis.
        Front Med. 2014; 1: 61
        • Pilotto A.
        • Sancarlo D.
        • Panza F.
        • et al.
        The multidimensional prognostic index (MPI), based on a comprehensive geriatric assessment predicts short- and long-term mortality in hospitalized older patients with dementia.
        J Alzheimer Dis. 2009; 18: 191-199
        • Soysal P.
        • Stubbs B.
        • Lucato P.
        • et al.
        Inflammation and frailty in the elderly: A systematic review and meta-analysis.
        Ageing Res Rev. 2016; 31: 1-8