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Association of polypharmacy and hyperpolypharmacy with frailty states: a systematic review and meta-analysis

  • Palmer, Katie1
  • Villani, Emanuele R.2
  • Vetrano, Davide L.2, 3
  • Cherubini, Antonio4
  • Cruz-Jentoft, Alfonso J.5
  • Curtin, Denis6
  • Denkinger, Michael7
  • Gutiérrez-Valencia, Marta8
  • Guðmundsson, Adalsteinn9, 10
  • Knol, Wilma11
  • Mak, Diane V.11
  • O’Mahony, Denis6
  • Pazan, Farhad12
  • Petrovic, Mirko13
  • Rajkumar, Chakravarthi14
  • Topinkova, Eva15
  • Trevisan, Catarina16
  • van der Cammen, Tischa J. M.17, 18, 19
  • van Marum, Rob J.20, 21
  • Wehling, Martin22
  • And 3 more
  • 1 Fondazione Ospedale San Camillo IRCCS, Via Alberoni 70, Venezia, 30126, Italia , Venezia (Italy)
  • 2 Università Cattolica del Sacro Cuore, Department of Geriatrics, Centro Medicina dell’Invecchiamento, Rome, Italy , Rome (Italy)
  • 3 NVS, Karolinska Institutet, Aging Research Center, Stockholm, Sweden , Stockholm (Sweden)
  • 4 Geriatria, Accettazione geriatrica e Centro di ricerca per l’invecchiamento, IRCCS INRCA, Ancona, Italy , Ancona (Italy)
  • 5 Hospital Universitario Ramón y Cajal (IRYCIS), Servicio de Geriatría, Madrid, Spain , Madrid (Spain)
  • 6 University College Cork, Cork University Hospital, Department of Medicine, Department of Geriatric Medicine, Cork, Ireland , Cork (Ireland)
  • 7 Ulm University, Agaplesion Bethesda Clinic Ulm, Geriatric Center Ulm/Alb-Donau and Geriatric Research Unit, Ulm, Germany , Ulm (Germany)
  • 8 Universidad Pública de Navarra (UPNA), Complejo Hospitalario de Navarra (CHN), IdiSNA, Department of Pharmacy, Navarrabiomed, Pamplona, Navarra, Spain , Pamplona (Spain)
  • 9 University of Iceland, Faculty of Medicine, Reykjavík, Iceland , Reykjavík (Iceland)
  • 10 Landspitali University Hospital, Department of Geriatrics, Reykjavík, Iceland , Reykjavík (Iceland)
  • 11 University Medical Center Utrecht, Utrecht University, Department of Geriatric Medicine, Expertise Centre Pharmacotherapy in Old Persons, Utrecht, The Netherlands , Utrecht (Netherlands)
  • 12 Heidelberg University, Institute for Clinical Pharmacology, Medical Faculty Mannheim, Mannheim, Germany , Mannheim (Germany)
  • 13 Ghent University, Department of Internal Medicine, Section of Geriatrics, Ghent, Belgium , Ghent (Belgium)
  • 14 University of Sussex, Department of Medicine, Brighton and Sussex Medical School, Brighton, UK , Brighton (United Kingdom)
  • 15 Charles University, General Faculty Hospital, Department of Geriatrics, First Faculty of Medicine, Prague, Czech Republic , Prague (Czechia)
  • 16 University of Padova, Department of Medicine, Geriatrics Division, Padua, Italy , Padua (Italy)
  • 17 Delft University of Technology, Faculty of Industrial Design Engineering, Delft, The Netherlands , Delft (Netherlands)
  • 18 Erasmus MC, University Medical Center Rotterdam, Department of Internal Medicine, Division of Geriatrics, Rotterdam, The Netherlands , Rotterdam (Netherlands)
  • 19 Brighton and Sussex Medical School, Academic Department of Geriatrics, Brighton, East Sussex, UK , Brighton (United Kingdom)
  • 20 Amsterdam UMC, Vrije Universiteit Amsterdam, Department of General Practice and Old Age Medicine, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 21 Jeroen Bosch Hospital, Department of Geriatrics, ‘s-Hertogenbosch, The Netherlands , ‘s-Hertogenbosch (Netherlands)
  • 22 University of Heidelberg, Medical Faculty Mannheim, Clinical Pharmacology, Heidelberg, Germany , Heidelberg (Germany)
Published Article
European Geriatric Medicine
Springer International Publishing
Publication Date
Nov 07, 2018
DOI: 10.1007/s41999-018-0124-5
Springer Nature


PurposeTo investigate: (1) the cross-sectional association between polypharmacy, hyperpolypharmacy and presence of prefrailty or frailty; (2) the risk of incident prefrailty or frailty in persons with polypharmacy, and vice versa.MethodsA systematic review and meta-analysis was performed according to PRISMA guidelines. We searched PubMed, Web of Science, and Embase from 01/01/1998 to 5/2/2018. Pooled estimates were obtained through random effect models and Mantel–Haenszel weighting. Homogeneity was assessed with the I2 statistic and publication bias with Egger’s and Begg’s tests.ResultsThirty-seven studies were included. The pooled proportion of polypharmacy in persons with prefrailty and frailty was 47% (95% CI 33–61) and 59% (95% CI 42–76), respectively. Increased odds ratio of polypharmacy were seen for prefrail (pooled OR = 1.52; 95% CI 1.32–1.79) and frail persons (pooled OR = 2.62, 95% CI 1.81–3.79). Hyperpolypharmacy was also increased in prefrail (OR = 1.95; 95% CI 1.41–2.70) and frail (OR = 6.57; 95% CI 9.57–10.48) persons compared to robust persons. Only seven longitudinal studies reported data on the risk of either incident prefrailty or frailty in persons with baseline polypharmacy. A significant higher odds of developing prefrailty was found in robust persons with polypharmacy (pooled OR = 1.30; 95% CI 1.12–1.51). We found no papers investigating polypharmacy incidence in persons with prefrailty/frailty.ConclusionsPolypharmacy is common in prefrail and frail persons, and these individuals are also more likely to be on extreme drug regimens, i.e. hyperpolypharmacy, than robust older persons. More research is needed to investigate the causal relationship between polypharmacy and frailty syndromes, thereby identifying ways to jointly reduce drug burden and prefrailty/frailty in these individuals.Prospero registration numberCRD42018104756.

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