Clinical outcomes in patients with atrial fibrillation receiving amiodarone on NOACs vs. warfarin
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.
KeywordsAtrial fibrillation New oral anticoagulants Vitamin K antagonists Amiodarone Clinical outcomes
apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation trial
cytochrome p-450 3A4
- ENGAGE AF-TIMI 48
effective anticoagulation with factor Xa next generation in atrial fibrillation trial
internationalized normalized ratio
long-standing persistent atrial fibrillation
non-valvular atrial fibrillation
new oral anticoagulant
randomized evaluation of long-term anticoagulation therapy trial
- ROCKET AF
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
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.
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