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Polypharmacy and mortality: new insights from a large cohort of older adults by detection of effect modification by multi-morbidity and comprehensive correction of confounding by indication

  • Pharmacoepidemiology and Prescription
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Abstract

Purpose

The objective was to investigate whether the association of polypharmacy with non-cancer mortality is independent from comorbidity and is not a result of confounding by indication.

Methods

Analyses were conducted in 2687 participants of a German, population-based cohort of older adults with data collection 2008–2010. Polypharmacy was defined as ≥5 drugs and hyperpolypharmacy as ≥10 drugs. Drugs without relevant propensity of causing adverse drug reactions or drug-drug interactions were not counted. Confounding by indication was addressed by model adjustment for a propensity score for polypharmacy.

Results

The median age of study participants was 70 years, 10.7% had multi-morbidity, and 47.4% took five drugs or more (8.6% took ≥10 drugs). During 4.4 years of follow-up, 87 participants died of a cause other than cancer. Statistically significant, more than twofold increased non-cancer mortality was observed for subjects with polypharmacy or hyperpolypharmacy in a model adjusted for age, sex, education, lifestyle variables, and comorbidity, but associations lost statistical significance after additional adjustment for a propensity score for polypharmacy. However, a significant interaction of hyperpolypharmacy and multi-morbidity was detected (p = 0.019). The hazard ratio for the association of hyperpolypharmacy with non-cancer mortality was 1.42 (95%CI 0.57; 3.57) in subjects without multi-morbidity and 0.51 (95%CI 0.11; 2.27) in subjects with multi-morbidity.

Conclusions

Polypharmacy was not independently associated with non-cancer mortality. This study highlights the importance to adjust for confounding by indication in studies on polypharmacy by a propensity score. The detected interaction suggests that hyperpolypharmacy can be indicated in subjects with multi-morbidity and may only be harmful in subjects without multi-morbidity.

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Acknowledgements

This study was funded by the Federal Ministry of Education and Research (Berlin, Germany) [grant number 01GY1320A]. We are thankful to Walter Emil Haefeli and his employees at the Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, who designed the data collection procedure about drugs at the home visit and prepared the data. Andreas Meid (same institution) was one of the pharmacists who judged the ATC codes of all drugs available on the German market regarding their propensity of causing ADRs or drug-drug interaction.

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Authors and Affiliations

  1. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany

    Ben Schöttker, Kai-Uwe Saum, Dana Clarissa Muhlack, Liesa Katharina Hoppe & Hermann Brenner

  2. Network Aging Research, University of Heidelberg, Heidelberg, Germany

    Ben Schöttker, Dana Clarissa Muhlack, Liesa Katharina Hoppe & Hermann Brenner

  3. Institute of Health Care and Social Sciences, FOM University, Essen, Germany

    Ben Schöttker

  4. Saarland Cancer Registry, Saarbrücken, Germany

    Bernd Holleczek

Authors
  1. Ben Schöttker
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  2. Kai-Uwe Saum
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  3. Dana Clarissa Muhlack
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  4. Liesa Katharina Hoppe
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  5. Bernd Holleczek
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  6. Hermann Brenner
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Corresponding author

Correspondence to Ben Schöttker.

Ethics declarations

The ESTHER study was approved by the ethics committees of the Medical Faculty of the University of Heidelberg and the Medical Association of Saarland and is being conducted in accordance with the Declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.

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Schöttker, B., Saum, KU., Muhlack, D.C. et al. Polypharmacy and mortality: new insights from a large cohort of older adults by detection of effect modification by multi-morbidity and comprehensive correction of confounding by indication. Eur J Clin Pharmacol 73, 1041–1048 (2017). https://doi.org/10.1007/s00228-017-2266-7

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  • DOI: https://doi.org/10.1007/s00228-017-2266-7

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