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

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Abstract

Purpose

To 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.

Methods

A 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.

Results

Thirty-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.

Conclusions

Polypharmacy 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 number

CRD42018104756.

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Acknowledgements

Composition of European Geriatric Medicine Society special interest group on Pharmacology: Marit Bakken, Jean-Pierre Baeyens, Athanase Benetos, Antonio Cherubini, Peter Crome, Alfonso J. Cruz-Jentoft, Michael Denkinger, Tomas Frühwald, Paul Gallagher, Adalsteinn Guðmundsson, Stephen Jackson, Paul Jansen, Wilma Knol, Denis O’Mahony, Graziano Onder, Desmond O’Neill, Mirko Petrovic, Alberto Pilotto, Elina Ronnemaa, Jens-Ulrik Rosholm, José Antonio Serra, George Soulis, Tischa JM van der Cammen, Nathalie van der Velde, Rob van Marum, Martin Wehling, Gijsbertus Ziere.

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Authors and Affiliations

  1. Fondazione Ospedale San Camillo IRCCS, Via Alberoni 70, 30126, Venezia, Italia

    Katie Palmer

  2. Department of Geriatrics, Centro Medicina dell’Invecchiamento, Università Cattolica del Sacro Cuore, Rome, Italy

    Emanuele R. Villani, Davide L. Vetrano, Roberto Bernabei & Graziano Onder

  3. Aging Research Center, NVS, Karolinska Institutet, Stockholm, Sweden

    Davide L. Vetrano

  4. Geriatria, Accettazione geriatrica e Centro di ricerca per l’invecchiamento, IRCCS INRCA, Ancona, Italy

    Antonio Cherubini

  5. Servicio de Geriatría, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain

    Alfonso J. Cruz-Jentoft

  6. Department of Medicine, Department of Geriatric Medicine, University College Cork, Cork University Hospital, Cork, Ireland

    Denis Curtin & Denis O’Mahony

  7. Agaplesion Bethesda Clinic Ulm, Geriatric Center Ulm/Alb-Donau and Geriatric Research Unit, Ulm University, Ulm, Germany

    Michael Denkinger

  8. Department of Pharmacy, Navarrabiomed, Universidad Pública de Navarra (UPNA), Complejo Hospitalario de Navarra (CHN), IdiSNA, Pamplona, Navarra, Spain

    Marta Gutiérrez-Valencia

  9. Faculty of Medicine, University of Iceland, Reykjavík, Iceland

    Adalsteinn Guðmundsson

  10. Department of Geriatrics, Landspitali University Hospital, Reykjavík, Iceland

    Adalsteinn Guðmundsson

  11. Department of Geriatric Medicine, Expertise Centre Pharmacotherapy in Old Persons, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

    Wilma Knol & Diane V. Mak

  12. Institute for Clinical Pharmacology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Farhad Pazan

  13. Department of Internal Medicine, Section of Geriatrics, Ghent University, Ghent, Belgium

    Mirko Petrovic

  14. Department of Medicine, Brighton and Sussex Medical School, University of Sussex, Brighton, UK

    Chakravarthi Rajkumar

  15. Department of Geriatrics, First Faculty of Medicine, Charles University, General Faculty Hospital, Prague, Czech Republic

    Eva Topinkova

  16. Department of Medicine, Geriatrics Division, University of Padova, Padua, Italy

    Catarina Trevisan

  17. Faculty of Industrial Design Engineering, Delft University of Technology, Delft, The Netherlands

    Tischa J. M. van der Cammen

  18. Department of Internal Medicine, Division of Geriatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    Tischa J. M. van der Cammen & Gijsbertus Ziere

  19. Academic Department of Geriatrics, Brighton and Sussex Medical School, Brighton, East Sussex, UK

    Tischa J. M. van der Cammen

  20. Department of General Practice and Old Age Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

    Rob J. van Marum

  21. Department of Geriatrics, Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands

    Rob J. van Marum

  22. Medical Faculty Mannheim, Clinical Pharmacology, University of Heidelberg, Heidelberg, Germany

    Martin Wehling

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  1. Katie Palmer
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On behalf of the European Geriatric Medicine Society Pharmacology special interest group

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Correspondence to Katie Palmer.

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The European Geriatric Medicine Society Pharmacology special interest group members are listed in the Acknowledgement section.

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Palmer, K., Villani, E.R., Vetrano, D.L. et al. Association of polypharmacy and hyperpolypharmacy with frailty states: a systematic review and meta-analysis. Eur Geriatr Med 10, 9–36 (2019). https://doi.org/10.1007/s41999-018-0124-5

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