The Concomitant Therapy of Direct Oral Anticoagulants with Amiodarone in Atrial Fibrillation: A Meta-analysis

Background The concomitant therapy of amiodarone with direct oral anticoagulants (DOACs) significantly increases the concentrations of DOACs and may increase the bleeding risks. Multiple real-world studies compared the concomitant therapy of amiodarone and DOACs versus the DOAC alone, but their main...

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Main Authors: Kazuhiko Kido PharmD, PhD, Mikiko Shimizu PhD, Tsuyoshi Shiga MD, PhD, Masayuki Hashiguchi PhD
Format: Article
Language:English
Published: SAGE Publishing 2025-06-01
Series:Journal of Cardiovascular Pharmacology and Therapeutics
Online Access:https://doi.org/10.1177/10742484251351148
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author Kazuhiko Kido PharmD, PhD
Mikiko Shimizu PhD
Tsuyoshi Shiga MD, PhD
Masayuki Hashiguchi PhD
author_facet Kazuhiko Kido PharmD, PhD
Mikiko Shimizu PhD
Tsuyoshi Shiga MD, PhD
Masayuki Hashiguchi PhD
author_sort Kazuhiko Kido PharmD, PhD
collection DOAJ
description Background The concomitant therapy of amiodarone with direct oral anticoagulants (DOACs) significantly increases the concentrations of DOACs and may increase the bleeding risks. Multiple real-world studies compared the concomitant therapy of amiodarone and DOACs versus the DOAC alone, but their main findings were contradictory. Methods A meta-analysis compared the concomitant therapy of amiodarone and DOACs versus DOACs monotherapy. Database searches through May 1, 2025, were performed. The primary outcome was major bleeding. The secondary outcomes included stroke or systemic embolism, any bleeding, all-cause mortality, gastrointestinal bleeding, and intracranial bleeding. Results This meta-analysis included a total of nine studies. There were no significant differences in major bleeding between the concomitant therapy of amiodarone and DOAC and DOAC monotherapy groups (OR 1.12; 95% CI 0.98, 1.27; P  = .09; I 2  = 64%). No significant differences in any bleeding (OR 1.18; 95% CI 0.88, 1.57; P  = .27; I 2  = 77%), gastrointestinal bleeding (OR 0.97; 95% CI 0.84, 1.11; P  = .65; I 2  = 56%), and intracranial bleeding (OR 1.14; 95% CI 1.00, 1.30; P  = .05; I 2  = 32%) were also found between the two groups. No significant differences in stroke or systemic embolism were found between the two groups (OR 0.86; 95% CI 0.74, 1.00; P  = .05; I 2  = 34%). Conclusion and Relevance The concomitant therapy of amiodarone and DOACs did not significantly increase the bleeding risks or decrease the risk of stroke or systemic embolism compared to the DOAC monotherapy. The drug-drug interactions between amiodarone and DOACs may not be clinically significant.
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spelling doaj-art-41d3abeb4ca44a049db389a00949d5e72025-08-20T03:22:45ZengSAGE PublishingJournal of Cardiovascular Pharmacology and Therapeutics1940-40342025-06-013010.1177/10742484251351148The Concomitant Therapy of Direct Oral Anticoagulants with Amiodarone in Atrial Fibrillation: A Meta-analysisKazuhiko Kido PharmD, PhD0Mikiko Shimizu PhD1Tsuyoshi Shiga MD, PhD2Masayuki Hashiguchi PhD3 Department of Clinical Pharmacy, School of Pharmacy, , Morgantown, WV, USA Department of Pharmaceutics and Pharmacometrics, School of Pharmacy, Shujitsu University, Okayama, Japan Department of Clinical Pharmacology and Therapeutics, The Jikei University School of Medicine, Tokyo, Japan Department of Clinical Pharmacology and Therapeutics, The Jikei University School of Medicine, Tokyo, JapanBackground The concomitant therapy of amiodarone with direct oral anticoagulants (DOACs) significantly increases the concentrations of DOACs and may increase the bleeding risks. Multiple real-world studies compared the concomitant therapy of amiodarone and DOACs versus the DOAC alone, but their main findings were contradictory. Methods A meta-analysis compared the concomitant therapy of amiodarone and DOACs versus DOACs monotherapy. Database searches through May 1, 2025, were performed. The primary outcome was major bleeding. The secondary outcomes included stroke or systemic embolism, any bleeding, all-cause mortality, gastrointestinal bleeding, and intracranial bleeding. Results This meta-analysis included a total of nine studies. There were no significant differences in major bleeding between the concomitant therapy of amiodarone and DOAC and DOAC monotherapy groups (OR 1.12; 95% CI 0.98, 1.27; P  = .09; I 2  = 64%). No significant differences in any bleeding (OR 1.18; 95% CI 0.88, 1.57; P  = .27; I 2  = 77%), gastrointestinal bleeding (OR 0.97; 95% CI 0.84, 1.11; P  = .65; I 2  = 56%), and intracranial bleeding (OR 1.14; 95% CI 1.00, 1.30; P  = .05; I 2  = 32%) were also found between the two groups. No significant differences in stroke or systemic embolism were found between the two groups (OR 0.86; 95% CI 0.74, 1.00; P  = .05; I 2  = 34%). Conclusion and Relevance The concomitant therapy of amiodarone and DOACs did not significantly increase the bleeding risks or decrease the risk of stroke or systemic embolism compared to the DOAC monotherapy. The drug-drug interactions between amiodarone and DOACs may not be clinically significant.https://doi.org/10.1177/10742484251351148
spellingShingle Kazuhiko Kido PharmD, PhD
Mikiko Shimizu PhD
Tsuyoshi Shiga MD, PhD
Masayuki Hashiguchi PhD
The Concomitant Therapy of Direct Oral Anticoagulants with Amiodarone in Atrial Fibrillation: A Meta-analysis
Journal of Cardiovascular Pharmacology and Therapeutics
title The Concomitant Therapy of Direct Oral Anticoagulants with Amiodarone in Atrial Fibrillation: A Meta-analysis
title_full The Concomitant Therapy of Direct Oral Anticoagulants with Amiodarone in Atrial Fibrillation: A Meta-analysis
title_fullStr The Concomitant Therapy of Direct Oral Anticoagulants with Amiodarone in Atrial Fibrillation: A Meta-analysis
title_full_unstemmed The Concomitant Therapy of Direct Oral Anticoagulants with Amiodarone in Atrial Fibrillation: A Meta-analysis
title_short The Concomitant Therapy of Direct Oral Anticoagulants with Amiodarone in Atrial Fibrillation: A Meta-analysis
title_sort concomitant therapy of direct oral anticoagulants with amiodarone in atrial fibrillation a meta analysis
url https://doi.org/10.1177/10742484251351148
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