Polypharmacy, adverse outcomes, and treatment effectiveness in patients ≥75 with atrial fibrillation

Nemin Chen, Aniqa B. Alam, Pamela L. Lutsey, Richard F. Maclehose, J’Neka S. Claxton, Lin Y. Chen, Alanna M. Chamberlain, Alvaro Alonso

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21 Scopus citations


BACKGROUND: Polypharmacy is highly prevalent in elderly people with chronic conditions, including atrial fibrillation (AF). The impact of polypharmacy on adverse outcomes and on treatment effectiveness in elderly patients with AF remains unaddressed. METHODS AND RESULTS: We studied 338 810 AF patients ≥75 years of age enrolled in the MarketScan Medicare Supplemental database in 2007–2015. Polypharmacy was defined as ≥5 active prescriptions at AF diagnosis (defined by the presence of International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes) based on outpatient pharmacy claims. AF treatments (oral anticoagulation, rhythm and rate control) and cardiovascular end points (ischemic stroke, bleeding, heart failure) were defined based on inpatient, outpatient, and pharmacy claims. Multivariable Cox models were used to estimate associations of polypharmacy with cardiovascular end points and the interaction between polypharmacy and AF treatments in relation to cardiovascular end points. Prevalence of polypharmacy was 52%. Patients with polypharmacy had increased risk of major bleeding (hazard ratio [HR], 1.16; 95% CI, 1.12–1.20) and heart failure (HR, 1.33; 95% CI, 1.29–1.36) but not ischemic stroke (HR, 0.96; 95% CI, 0.92–1.00), compared with those not receiving polypharmacy. Polypharmacy status did not consistently modify the effectiveness of oral anticoagulants. Rhythm control (versus rate control) was more effective in preventing heart failure hospitalization in patients not receiving polypharmacy (HR, 0.87; 95% CI, 0.76–0.99) than among those with polypharmacy (HR, 0.98; 95% CI, 0.91–1.07; P=0.02 for interaction). CONCLUSION: Polypharmacy is common among patients ≥75 with AF, is associated with adverse outcomes, and may modify the effectiveness of AF treatments. Optimizing management of polypharmacy in AF patients ≥75 may lead to improved outcomes.

Original languageEnglish (US)
Article numbere015089
JournalJournal of the American Heart Association
Issue number11
StatePublished - 2020

Bibliographical note

Funding Information:
Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under award number R21AG058445 and the National Heart, Lung, and Blood Institute of the National Institutes of Health under award numbers R01HL122200 and K24HL148521. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was also supported by American Heart Association grant 16EIA26410001 (Alonso).

Publisher Copyright:
© 2020 The Authors and Mayo Clinic. Published on behalf of the American Heart Association, Inc., by Wiley.


  • Adverse outcomes
  • Atrial fibrillation
  • Polypharmacy


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