Clinical outcomes in patients with atrial fibrillation receiving amiodarone on NOACs vs. warfarin

  • Ricardo Avendano
  • Jorge Romero
  • Florentino Lupercio
  • Juan Carlos Diaz
  • Renato Quispe
  • Anjani Golive
  • Andrea Natale
  • Mario J. Garcia
  • Andrew K. Krumerman
  • Luigi Di BiaseEmail author



Amiodarone is a potent inhibitor of the CYP450:3A4 and inhibitor of the P-glycoprotein, both of which metabolize new oral anticoagulants (NOACs). Patients who are on NOACs and are concomitantly treated with amiodarone may have a higher risk of major bleeding according to recent retrospective trials. Whether this increased risk outweighs the benefits of NOACs compared to warfarin is unknown. We aimed to compare clinical outcomes between NOACs and warfarin in patients with atrial fibrillation (AF) being treated with amiodarone.


We performed a systematic review of MEDLINE, Cochrane, and Embase for randomized controlled trials that compared NOACs to warfarin for prophylaxis of ischemic stroke/thromboembolic events (TEs) in patients with AF and reported outcomes on TE, major bleeding, and intracranial bleeding (ICB). Risk ratio (RR) and 95% confidence intervals were measured using the Mantel-Haenszel method. Fixed effects model was used, and if heterogeneity (I2) was > 25%, effects were analyzed using a random model.


A total of four studies comparing NOACs to warfarin were included in the analysis. The total number of patients on amiodarone was 6197. Mean follow up was 23 ± 5 months. No statistically significant difference for TE prevention (RR, 0.73; 95% CI 0.50–1.07), major bleeding (RR, 1.02; 95% CI 0.68–1.53), or ICB outcomes (RR, 0.58; 95% CI 0.22–1.51) between patients on NOACs + amiodarone when compared to patients on warfarin + amiodarone.


Among patients with AF taking amiodarone, there is no increased risk of stroke, major bleeding, or ICB with NOACs compared to warfarin.


Atrial fibrillation New oral anticoagulants Vitamin K antagonists Amiodarone Clinical outcomes 



atrial fibrillation


apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation trial


cytochrome p-450 3A4


effective anticoagulation with factor Xa next generation in atrial fibrillation trial


intracranial bleeding


internationalized normalized ratio


long-standing persistent atrial fibrillation


non-valvular atrial fibrillation


new oral anticoagulant


oral anticoagulation




randomized evaluation of long-term anticoagulation therapy trial


the rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin k antagonism for prevention of stroke and embolism trial in atrial fibrillation


ischemic stroke/thromboembolic events


vitamin K antagonist


Author Contributions

RA, J.R, and L.D.B designed the original research idea. R.A and J.R searched studies and extracted data independently. J.R., R.A., F.L., J.C.D., R.Q., A.G., A.N., M.J.G., A.K.K, and L.D.B drafted and approved the present manuscript.

Compliance with ethical standards

Conflict of interest

Dr. Di Biase is a consultant for Biosense Webster, Boston Scientific, and St. Jude Medical, and has received speaker honoraria/travel from Medtronic, St. Jude Medical, Atricure, EPiEP, and Biotronik. The other authors have no pertinent conflicts of interest to report.

Supplementary material

10840_2018_427_MOESM1_ESM.docx (42 kb)
ESM 1 (DOCX 42 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Montefiore Medical CenterAlbert Einstein College of MedicineBronxUSA
  2. 2.Texas Cardiac Arrhythmia Institute at St. David’s Medical CenterAustinUSA

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