Polypharmacy occurrence and the related risk of premature death among older adults in Denmark: A nationwide register-based cohort study

PLoS One. 2022 Feb 23;17(2):e0264332. doi: 10.1371/journal.pone.0264332. eCollection 2022.

Abstract

Background: Polypharmacy, defined as the concurrent use of ≥5 medications, increases the risk of drug-drug and drug-disease interactions as well as non-adherence to drug therapy. This may have negative health consequences particularly among older adults due to age-related pharmacokinetic and pharmacodynamic changes. This study aims to uncover the occurrence of polypharmacy among older adults in Denmark and investigate how polypharmacy relates to mortality.

Method: This nationwide register-based study included 1,338,058 adults aged 65+ years between January 2013 and December 2017 in Denmark. Polypharmacy prevalence was measured at time of inclusion while incidence and the association between polypharmacy and mortality were measured over the five-year follow-up using Cox regression. In an attempt to adjust for confounding by indication, propensity scores with overlap weighting were introduced to the regression model.

Results: At time of inclusion, polypharmacy prevalence was 29% and over the five years follow-up, 47% of the remaining adults transitioned into polypharmacy. Identified risk factors included multimorbidity (2+ morbidities: HR = 3.51; 95% CI = 3.48-3.53), age (95+ years: HR = 2.85; 95% CI = 2.74-2.96), socioeconomic factors (Highest income quartile: HR = 0.81; 95% CI = 0.80-0.81), region of birth region (Non-western migrants: HR = 0.77; 95% CI = 0.75-0.79), marital status (Divorced: HR = 1.10; 95% CI = 1.10-1.12) and year of inclusion (2017: HR = 1.19; 95% CI = 1.19-1.22). Further analyses showed that polypharmacy involves many different drug cocktails with medication for the cardiovascular system (95%), blood and blood-forming organs (69%), alimentary tract and metabolism (61%) and nervous system (54%) contributing the most. After adjustment for propensity scores with OW, both polypharmacy (HR = 3.48, CI95% = 3.41-3.54) and excessive polypharmacy (HR = 3.48, CI95% = 3.43-3.53) increased the risk of death substantially.

Conclusion: A considerable proportion of older adults in Denmark were exposed to polypharmacy dependent on health status, socio-economic status, and societal factors. The associated three- to four-fold mortality risk indicate a need for further exploration of the appropriateness of polypharmacy among older adults.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Denmark
  • Female
  • Humans
  • Male
  • Mortality, Premature / trends*
  • Polypharmacy / statistics & numerical data*
  • Registries / statistics & numerical data*

Grants and funding

AVJP, LHM and RGJW was supported by grants from Novo Nordisk Foundation [NNF17OC0027812] (https://novonordiskfonden.dk/en/), while MK was funded by Nordea Fonden [02-2017-1749] (https://nordeafonden.dk/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.