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Association between concurrent use of amiodarone and DOACs and risk of bleeding in patients with atrial fibrillation

Shurrab M, Jackevicius CA, Austin PC, Tu K, Qiu F, Singh SM, Crystal E, Caswell J, Michael F, Andrade JG, Ko DT. Am J Cardiol. 2022; Nov 4 [Epub ahead of print]. DOI: https://doi.org/10.1016/j.amjcard.2022.10.031


Amiodarone is a commonly used pharmacotherapy in patients with atrial fibrillation (AF), with a potential for drug-drug interactions with direct oral anticoagulants (DOACs). We aimed to assess the bleeding risk after co-prescription of amiodarone and DOACs among adults with AF. We conducted a population-based, nested case-control study in Ontario, Canada. The study population included all patients with AF aged >66 years on a DOAC between April 1, 2011 and March 31, 2018. Cases were patients admitted with major bleeding (index date). Controls were matched in a 2:1 ratio to cases. We categorized exposure to amiodarone before the index date as: (1) current users (amiodarone within 60 days), (2) past users (amiodarone within 61 to 140 days), and (3) unexposed (no amiodarone prescription or amiodarone prescription >140 days before index date). Conditional logistic regression models were used to examine the association between bleeding and amiodarone co-prescription. Among 86,679 patients with AF on a DOAC, we identified 2,766 cases (3.2%) admitted with major bleeding. The median age of patients with AF was 80 years (interquartile range 75 to 85); 48.3% were women. After multivariable adjustment, there was a significant association between major bleeding and current use of amiodarone (adjusted odds ratio 1.53; 95% confidence interval 1.24 to 1.89, p <0.001) but no significant association between major bleeding and past use of amiodarone (adjusted odds ratio 1.13, 95% confidence interval 0.76 to 1.68, p = 0.545) compared with the unexposed group. In conclusion, among older patients with AF on a DOAC, there was 53% increased odds of major bleeding with the current use of amiodarone.

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