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

Author:

Grymonprez Maxim1ORCID,Petrovic Mirko2,De Backer Tine L.3,Steurbaut Stephane45,Lahousse Lies16

Affiliation:

1. Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium

2. Department of Geriatrics, Ghent University Hospital, Ghent, Belgium

3. Department of Cardiology, Ghent University Hospital, Ghent, Belgium

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

6. Department of Epidemiology, Erasmus Medical Center, Rotterdam, CA, The Netherlands

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.

Funder

Research Foundation Flanders

Publisher

Georg Thieme Verlag KG

Subject

Hematology

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