Association Between Concurrent Use of Amiodarone and DOACs and Risk of Bleeding in Patients With Atrial Fibrillation

Am J Cardiol. 2023 Jan 1:186:58-65. doi: 10.1016/j.amjcard.2022.10.031. Epub 2022 Nov 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged, 80 and over
  • Amiodarone* / adverse effects
  • Anticoagulants / adverse effects
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Atrial Fibrillation* / epidemiology
  • Case-Control Studies
  • Female
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Male
  • Ontario / epidemiology
  • Stroke* / epidemiology


  • Amiodarone
  • Anticoagulants