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Higher risk of bleeding events associated with concomitant use of amiodarone and direct oral anticoagulants
Clinical Question
For patients with atrial fibrillation, is the combined use of amiodarone with apixaban or rivaroxaban associated with a greater risk of bleeding-related hospitalizations?
Bottom line
In this study, the concomitant use of amiodarone with a DOAC, compared with either sotalol or flecainide plus a DOAC, by older patients with atrial fibrillation was associated with a higher risk of bleeding-related hospitalizations. Although the investigators used statistical methodology to balance baseline characteristics between the 2 groups, it is possible that residual confounders remained, and that inherent differences in the patients who received amiodarone may have affected their bleeding risk. 2b
Reference
Study design: Cohort (retrospective)
Funding: Government
Setting: Inpatient (any location)
Synopsis
Drug-drug interaction between amiodarone and the direct oral anticoagulants (DOACs) apixaban and rivaroxaban inhibits elimination of the anticoagulants with a resultant increase in their plasma concentration. This study examined the risk of bleeding with concomitant use of amiodarone and apixaban or rivaroxaban. Using information from the United States Medicare beneficiary database, these investigators identified patients 65 years or older with atrial fibrillation who were taking apixaban or rivaroxaban and were given either amiodarone, sotalol, or flecainide for anti-arrhythmic therapy. Patients with chronic or end-stage kidney disease and those with recent bleeding-related hospitalization, stroke, or systemic embolism were excluded. The patients taking amiodarone (n = 54,977) were compared with the patients taking either sotalol or flecainide (n = 36,613). The total study cohort had a mean age of 76 years and 53% were female. Patients in the amiodarone group were older and had a higher percentage of comorbidities, including heart failure, myocardial infarction, diabetes, and chronic kidney disease. The differences in baseline characteristics between the 2 groups were balanced using propensity score overlap weighting methodology. The primary outcome was bleeding-related hospitalization consisting of either major hemorrhagic events (any intracranial bleeding or fatal extracranial bleeding) or nonfatal extracranial bleeding. As compared with the combination of sotalol or flecainide plus study DOAC, the use of amiodarone plus study DOAC was associated with a higher risk of the primary outcome (56.5 vs 39.0 events per 1000 person-years; hazard ratio [HR] = 1.44; 95% CI 1.27 - 1.63) and its individual components. Although there was no significant difference in ischemic stroke or systemic embolism between the 2 groups, there was an association between the amiodarone group and an increased risk of total mortality (HR = 1.28; 1.15 - 1.44), with a greater risk for deaths with recent evidence of bleeding (HR = 1.66, 95% CI 1.35-2.03).
Reviewer
Nita Shrikant Kulkarni, MD
Assistant Professor in Hospital Medicine
Northwestern University
Chicago, IL
Comments
Higher risk of bleeding events associated with concomitant u
Amio and DOAC not an unusual combination for A-fib. It is unlikely that a clinical trial will ever be conducted to sort out the issue at hand. HR are concerning for severe side effects. While I would never make a switch in patient's medication away from amio I would consider pointing the concern out to a patient I saw in the ED with the advice they seek an opinion from their most responsible physician as to whether a change in medication out to be considered. Would be helpful if this results of the paper were confirmed using other patient populations.
Impact assessment
Excellent
amiodarone and oral anticoagulants
good to know