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CC BY-NC-ND 4.0 · Thromb Haemost 2024; 124(02): 135-148
DOI: 10.1055/s-0043-1769735
Stroke, Systemic or Venous Thromboembolism

The Impact of Polypharmacy on the Effectiveness and Safety of Non-vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation

Maxim Grymonprez 
1   Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
,
Mirko Petrovic
2   Department of Geriatrics, Ghent University Hospital, Ghent, Belgium
,
Tine L. De Backer
3   Department of Cardiology, Ghent University Hospital, Ghent, Belgium
,
Stephane Steurbaut
4   Centre for Pharmaceutical Research, Research group of Clinical Pharmacology and Clinical Pharmacy, Vrije Universiteit Brussel, Jette, Belgium
5   Department of Hospital Pharmacy, UZ Brussel, Jette, Belgium
,
Lies Lahousse
1   Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
6   Department of Epidemiology, Erasmus Medical Center, Rotterdam, CA, The Netherlands
› Author Affiliations Funding This work was supported by grants from the Research Foundation Flanders (FWO) (grant number 11C0820N to Maxim Grymonprez).
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Comment on:

NOACs in Atrial Fibrillation Patients with PolypharmacyThromb Haemost 2024; 124(02): 149-151
DOI: 10.1055/s-0043-1776900

Abstract

Background Polypharmacy may affect outcomes in patients with atrial fibrillation (AF) using non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) due to interactions or reduced adherence, but comparative data are lacking. Therefore, the impact of polypharmacy on AF-related outcomes and benefit–risk profiles of NOACs in patients with polypharmacy were investigated.

Methods AF patients initiating anticoagulation between 2013 and 2019 were included using Belgian nationwide data. Inverse probability of treatment weighted Cox regression was used to investigate outcomes.

Results Among 254,478 AF patients, 167,847 (66.0%) used ≥5 drugs. Polypharmacy was associated with higher stroke or systemic embolism (stroke/SE) (adjusted hazard ratio [aHR]: 1.08, 95% confidence interval [CI]: 1.02–1.15), all-cause mortality (aHR: 1.45, 95% CI: 1.40–1.50), and major bleeding risks (aHR: 1.29, 95% CI: 1.23–1.35). Among patients with polypharmacy, NOACs were associated with lower stroke/SE (aHR: 0.68, 95% CI: 0.63–0.73), all-cause mortality (aHR: 0.80, 95% CI: 0.77–0.84), major bleeding (aHR: 0.92, 95% CI: 0.87–0.97), and intracranial bleeding risks (aHR: 0.77, 95% CI: 0.69–0.85), but higher gastrointestinal bleeding risks (aHR: 1.10, 95% CI: 1.01–1.19) compared to VKAs. Major bleeding risks were lower with apixaban (aHR: 0.79, 95% CI: 0.74–0.85), but nonsignificantly different with other NOACs compared to VKAs. Lower major bleeding risks were observed with dabigatran (aHR: 0.91, 95% CI: 0.85–0.97) and apixaban (aHR: 0.77, 95% CI: 0.73–0.81) compared to rivaroxaban, and with apixaban compared to dabigatran (HR: 0.83, 95% CI: 0.77–0.90) and edoxaban (HR: 0.77, 95% CI: 0.70–0.85).

Conclusion Polypharmacy was associated with increased thromboembolic, bleeding, and mortality risks in AF patients. NOACs had better benefit–risk profiles than VKAs in patients with polypharmacy.

Keywords

atrial fibrillation - polypharmacy - NOAC - thromboembolism

Data Availability Statement

Requests for the data underlying this article should be directed to the administrators of the Inter Mutualistic Agency (IMA) database or Minimal Hospital Dataset and is subject to approval.


Authors' Contribution

M.G. and L.L. contributed to the concept and design of the study. M.G. performed the statistical analysis, interpretation, and writing under the supervision of L.L. M.P., T.D.B., S.S., and L.L. revised the manuscript critically. All authors contributed to the article and approved the final version of the manuscript.


Supplementary Material



Publication History

Received: 20 February 2023

Accepted: 17 March 2023

Article published online:
27 June 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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