Original Article
Polypharmacy cutoff and outcomes: five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes

https://doi.org/10.1016/j.jclinepi.2012.02.018Get rights and content

Abstract

Objective

This study aimed to determine an optimal discriminating number of concomitant medications associated with geriatric syndromes, functional outcomes, and mortality in community-dwelling older men.

Study Design and Setting

Older men aged ≥70 years (n = 1,705), enrolled in the Concord Health and Aging in Men Project were studied. Receiver operating characteristic curve analysis using the Youden Index and the area under the curve was performed to determine discriminating number of medications in relation to each outcome.

Results

The highest value of the Youden Index for frailty was obtained for a cutoff point of 6.5 medications compared with a cutoff of 5.5 for disability and 3.5 for cognitive impairment. For mortality and incident falls, the highest value of Youden Index was obtained for a cutoff of 4.5 medications. For every one increase in number of medications, the adjusted odds ratios were 1.13 (95% confidence interval [CI] = 1.06–1.21) for frailty, 1.08 (95% CI = 1.00–1.15) for disability, 1.09 (95% CI = 1.04–1.15) for mortality, and 1.07 (95% CI = 1.03–1.12) for incident falls. There was no association between increasing number of medications and cognitive impairment.

Conclusion

The study supports the use of five or more medications in the current definition of polypharmacy to estimate the medication-related adverse effects for frailty, disability, mortality, and falls.

Introduction

What is new?

  • 1.

    There is a lack of agreement about the actual number of concomitant medications a person is taking that would be defined as polypharmacy.

  • 2.

    This study supports the widespread definition of polypharmacy that is linked to adverse outcomes as five or more medications.

  • 3.

    The number of concomitant medications was 6.5, 5.5, 4.5, and 4.5 medicines in association with frailty, disability, mortality, and falls, respectively.

  • 4.

    Our study provides evidence and clarification of the best cutoff value for the number of concomitant medications that should be used to identify older men at possible risk of different adverse outcomes.

Older adults display substantial variability in both beneficial and harmful responses to medications. With advanced age, there are age-associated changes in pharmacokinetics and pharmacodynamics, comorbidity, and patterns of medication use that may contribute to increased risk of adverse events [1], [2], [3]. Clinically, significant adverse outcomes of medication exposure in older adults include specific adverse drug reactions, falls, fractures, hospitalization, and physical and cognitive functional impairments [4], [5]. Polypharmacy, referred as the use of multiple medicines and/or the administration of more medicines than is clinically indicated, representing unnecessary medication use [6] has been associated with poorer clinical outcomes in observational studies of older adults [4], [7].

Although there is an evidence on the association of polypharmacy with adverse outcomes in older adults, there is a lack of agreement about the actual number of concomitant medications a person is taking that would be defined as “polypharmacy.” Some investigators have defined polypharmacy as the concomitant use of three or more medications [8] and others as the long-term simultaneous use of two or more medications [9]. Some studies did not explicitly state the minimum number of medicines used for the polypharmacy definition [10], [11]. In addition, further qualifiers have been explored to define types of polypharmacy including hyperpolypharmacy (use of 10 or more medications) [12], excessive polypharmacy (use of 10 or more medications) [13], [14], nonpolypharmacy (use of less than five medications) [15], and oligopharmacy (use of five or less medications) [16]. A recent study found that while the use of 10 or more concomitant medications was associated with poorer nutritional and functional status, and limitations in cognitive performance, the use of six to nine medications was only associated with poorer functional status in older people [15]. Identification and clarification of the best cutoff value for the number of concomitant medications that increase the risk of harm in older adults is important to guide prescribers and researchers considering polypharmacy in older people as a guide to improve medication-related outcomes. In addition, it may be that the thresholds in terms of number of concomitant medications above which risk increases depends on the adverse outcomes in question.

In the past, polypharmacy exposures were defined without specific clinical justification. To date, no study has been conducted to ascertain what number of medications should be considered excessively high on the basis of association with several different adverse outcomes. The aim of this study was to determine an optimal discriminating number of concomitant medications associated with geriatric syndromes, functional outcomes, and mortality in community-dwelling older men.

Section snippets

Setting and participants

Participants were community-dwelling older men enrolled in the Concord Health and Aging in Men Project (CHAMP), an ongoing cohort study in Sydney, Australia. Details of the study have been described elsewhere [17], [18], [19]. Eligible participants were only 70 years or older and living in a specific study area. The only exclusion criterion was living in a residential aged care facility. The Electoral Roll was chosen as the sampling frame for the study. In Australia, registration on the

Results

Characteristics of the study population are described in Table 1. The mean (range) age of the men in the study population was 76.9 (70.0–97.0), and the majority had completed secondary education (54%). Medication exposure was reported by 90% of the population. Mean number of medications reported in this population was 4.0 (2.9). A total of 158 (9.5%) participants were identified as being frail. Disability on ADL was observed in 8.3% of participants, and 12.5% were cognitively impaired (MCI or

Discussion

To our knowledge, this is the first study to investigate whether there is any justification for the number of medications concomitantly used to define the term “polypharmacy.” The findings provide support for the use of five or more medications in the current definition of polypharmacy to estimate the medication-related adverse effects for specific outcomes in older adults. This study was not performed to use number of medications as a diagnostic test nor to claim that polypharmacy causes

Acknowledgments

The CHAMP study is funded by the Australian National Health and Medical Research Council (NHMRC Project Grant No. 301916), Sydney Medical School Foundation and Aging and Alzheimer’s Research Foundation. The authors gratefully acknowledge the funding support from the Geoff and Elaine Penney Aging Research Unit.

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