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. 2024 Nov 5;13(21):e033513.
doi: 10.1161/JAHA.123.033513. Epub 2024 Nov 4.

Bleeding Associated With Antiarrhythmic Drugs in Patients With Atrial Fibrillation Using Direct Oral Anticoagulants: A Nationwide Population Cohort Study

Victor Chien-Chia Wu  1   2 , Chun-Li Wang  1 , Yu-Chang Huang  1 , Hui-Tzu Tu  3 , Yu-Tung Huang  3   4 , Chang-Fu Kuo  5   6 , Shao-Wei Chen  7 , Kuo-Chun Hung  1 , Ming-Shien Wen  1 , Shang-Hung Chang  1   3   8
Affiliations

Bleeding Associated With Antiarrhythmic Drugs in Patients With Atrial Fibrillation Using Direct Oral Anticoagulants: A Nationwide Population Cohort Study

Victor Chien-Chia Wu et al. J Am Heart Assoc. .

Abstract

Background: This study investigated drug-drug interactions in patients with atrial fibrillation taking both a direct oral anticoagulant (DOAC) and an antiarrhythmic drug.

Methods and results: Using data from the National Health Insurance database (2012-2018), we identified 78 805 patients with atrial fibrillation on DOACs, with 24 142 taking amiodarone, 8631 taking propafenone, 2784 taking dronedarone, 297 taking flecainide, 177 taking sotalol, and 42 772 on DOACs alone. Patients with bradycardia, heart block, heart failure, mitral stenosis, prosthetic valves, or incomplete data were excluded. Propensity score matching compared those taking both DOACs and antiarrhythmic drugs with those on DOACs alone. There was an increased risk of major bleeding in patients concomitantly taking DOACs with amiodarone when compared with matched patients taking DOACs alone (hazard ratio [HR],1.13 [95% CI, 1.04-1.23]; P=0.0044), particularly in patients taking dabigatran (HR, 1.19 [95% CI, 1.03-1.38]; P=0.0175). No significant difference in bleeding risk was found for propafenone, dronedarone, flecainide, or sotalol. The small sample sizes in the flecainide and sotalol groups limit interpretation. Notably, intracranial bleeding risk was higher in patients on DOACs and amiodarone, regardless of age. Additionally, patients <80 years old taking dabigatran with amiodarone or propafenone had a higher risk of gastrointestinal bleeding.

Conclusions: Concomitant use of DOACs with amiodarone, but not dronedarone or propafenone, increases the risk of major bleeding, particularly intracranial bleeding. This study provides new evidence to guide clinicians to tailor concomitant anticoagulation and antiarrhythmic therapy for patients with atrial fibrillation.

Keywords: DOAC; antiarrhythmic drugs; atrial fibrillation; bleeding; drug–drug interaction.

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Figures

Figure 1
Figure 1. Study design and flowchart of patient enrollment.
*For each antiarrhythmic drug user, we performed propensity score matching to find 1 comparable nonuser. AF indicates atrial fibrillation; and DOAC, direct oral anticoagulant.
Figure 2
Figure 2. Cox proportional hazard ratio of the event of major bleeding in patients with atrial fibrillation on DOACs concomitantly taking dronedarone, amiodarone, propafenone, flecainide, or sotalol compared with propensity‐matched patients on DOACs alone (A).
The major bleeding events are further separated into intracranial bleeding (B) and gastrointestinal bleeding (C). AAD indicates antiarrhythmic drug; DOACs, direct oral anticoagulants; and HR, hazard ratio.
Figure 3
Figure 3. Kaplan‐Meier curve for event‐free rate of major bleeding in patients with atrial fibrillation on DOACs concomitantly taking amiodarone, propafenone, dronedarone, flecainide, or sotalol propensity‐matched to patients with DOACs alone.
DOACs indicates direct oral anticoagulants.
See this image and copyright information in PMC

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