Elsevier

Journal of the American Pharmacists Association

Volume 57, Issue 6, November–December 2017, Pages 729-738.e10
Journal of the American Pharmacists Association

Science and Practice
Systematic Review
Association between polypharmacy and death: A systematic review and meta-analysis

https://doi.org/10.1016/j.japh.2017.06.002Get rights and content

Abstract

Objective

Polypharmacy has been linked to a myriad of adverse consequences, and escalating rates of polypharmacy present an emerging concern, particularly among older adults. This systematic review and meta-analysis summarizes the existing literature concerning the association between polypharmacy and mortality.

Data sources

A systematic literature review was done by searching the EMBASE, PubMed, Scopus, and International Pharmaceutical Abstract databases to identify studies assessing the association between polypharmacy and death published until June 2016.

Study selection

Studies that investigated the association between polypharmacy and mortality were eligible for this systematic review and meta-analysis.

Data extraction

Data were extracted by the first and second authors independently using a data extraction form. Disagreement was resolved by consensus. A meta-analysis was performed using random effect models. Heterogeneity was assessed using the I2 statistic.

Results

Forty-seven studies were included in this meta-analysis. The underlying populations were heterogeneous (I2= 91.5%). When defined as a discrete variable, pooled risk estimates demonstrated a significant association between polypharmacy and death (pooled-adjusted odds ratio [aOR] 1.08 [95% CI 1.04-1.12]). When defined categorically, a dose-response relationship was observed across escalating thresholds for defining polypharmacy. Categorical thresholds for polypharmacy using values of 1-4 medications, 5 medications, and 6-9 medications were significantly associated with death (P <0.05; aOR 1.24 [1.10-1.39], aOR 1.31 [1.17, 1.47], and aOR 1.59 [1.36-1.87], respectively). Excessive polypharmacy (ie, the use of 10 or more medications) was also associated with death (aOR 1.96 [1.42-2.71]).

Conclusions

Pooled risk estimates from this meta-analysis reveal that polypharmacy is associated with increased mortality risk, using both discrete and categorical definitions. The causality of this relationship remains unclear, but it emphasizes the need for approaches to health care delivery that achieve an optimal balance of risk and benefit in medication prescribing.

Section snippets

Data source and search strategy

Search terms were defined, and a systematic literature search was performed by the first and fourth authors using MEDLINE/PubMed, EMBASE, Scopus, and International Pharmaceutical Abstract from inception to June 2016 using the terms “polypharmacy” (e.g., multiple drugs used) and “death” (e.g., mortality, survival) without applying language or study design restrictions. Synonyms of polypharmacy and death suggested by the search engines and 2 studies1, 27 were used. The MEDLINE database was

Study characteristics

The systematic literature search retrieved 3892 nonredundant manuscripts. Two studies were found by reviewing reference lists.32, 33 According to the inclusion and exclusion criteria, 47 studies were selected, including 26 prospective cohort studies, 11 retrospective cohort studies, 5 case control studies, 4 clinical trials, and 1 cross-sectional study (Figure 1). Using the World Health Organization criteria to define the older adult population,34 36 studies were performed in populations with

Discussion

Polypharmacy has been characterized discretely as number of drugs and categorically using a variety of threshold definitions. In this systematic review and meta-analysis of 47 studies using both discrete and categorical approaches, polypharmacy was associated with mortality risk. Among categorical definitions, mortality risk increased in a dose-dependent fashion as threshold values defining polypharmacy increased. Moreover, these risk estimates were highly consistent with extrapolation of the

Conclusion

Characterizing the potential harms of polypharmacy is clearly of scientific interest, given the nearly 50 studies that were identified in this systematic review and meta-analysis. Our goal was to summarize the existing knowledge regarding this topic, which revealed support for a statistical association between polypharmacy and mortality. However, the clinical interpretation and significance of this association must be considered with caution. Regardless of academic efforts to document the

Acknowledgment

We thank Cheuk-Chun Szeto, MD, for providing detailed information from his publication.

Nattawut Leelakanok, BSc (Pharm), PhD, Graduate Student, College of Pharmacy, The University of Iowa, Iowa City, IA; Instructor, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand

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    Nattawut Leelakanok, BSc (Pharm), PhD, Graduate Student, College of Pharmacy, The University of Iowa, Iowa City, IA; Instructor, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand

    Andrea L. Holcombe, MSc, Graduate Student, College of Public Health, The University of Iowa, Iowa City, IA

    Brian C. Lund, PharmD, Core Investigator, Iowa City VA Health Care System, Iowa City, IA, and Clinical Assistant Professor, College of Public Health, University of Iowa, Iowa City, IA.

    Xiaomei Gu, BDS, MSc, MSLS, Clinical Education Librarian, Hardin Library for the Health Sciences, The University of Iowa, Iowa City, IA

    Marin L. Schweizer, PhD, Assistant Professor, Carver College of Medicine, University of Iowa, Iowa City, IA, and Core Investigator, Iowa City VA Health Care System, Iowa City, IA

    Disclosure: The authors declare no conflicts of interest or financial interests in any product or service mentioned in this article.

    Funding: Nattawut Leelakanok received support from The Royal Thai Government Scholarship. Additional support was contributed through Career Development Awards from the Health Services Research and Development Service, Department of Veterans Affairs (grant numbers CDA 10-017 [to Brian C. Lund] and CDA 11-215 [to Marin L. Schweizer]. This research did not receive any specific grant from funding agencies in the public, commercial, or nonprofit sectors.

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