Efficacy and Safety Outcomes of Direct Oral Anticoagulants and Amiodarone in Patients with Atrial Fibrillation

Florentino Lupercio, Jorge E. Romero, Bradley Peltzer, Carola Maraboto, David Briceno, Pedro Villablanca, Kevin J. Ferrick, Jay N. Gross, Soo G. Kim, John Devens Fisher, Luigi Di Biase, Andrew K. Krumerman

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Direct oral anticoagulants (DOACs) and amiodarone are widely used in the treatment of nonvalvular atrial fibrillation. The DOACs are P-glycoprotein (P-gp) and cytochrome p-450 (CYP3A4) substrates. Direct oral anticoagulant levels may be increased by the concomitant use of potent dual P-gp/CYP3A4 inhibitors, such as amiodarone, which can potentially translate into adverse clinical outcomes. We aimed to assess the efficacy and safety of drug-drug interaction by the concomitant use of DOACs and amiodarone. Methods: We performed a systematic review of MEDLINE, the Cochrane Central Register of Clinical Trials, and Embase, limiting our search to randomized controlled trials of patients with atrial fibrillation that have compared DOACs versus warfarin for prophylaxis of stroke or systemic embolism, to analyze the impact on stroke or systemic embolism, major bleeding, and intracranial bleeding risk in patients with concomitant use of amiodarone. Risk ratio (RR) 95% confidence intervals were measured using the Mantel-Haenszel method. The fixed effects model was used owing to heterogeneity (I 2) < 25%. Results: Four trials with a total of 71,683 patients were analyzed, from which 5% of patients (n = 3212) were concomitantly taking DOAC and amiodarone. We found no statistically significant difference for any of the clinical outcomes (stroke or systemic embolism [RR 0.85; 95% CI, 0.67-1.06], major bleeding [RR 0.91; 95% CI, 0.77-1.07], or intracranial bleeding [RR 1.10; 95% CI, 0.68-1.78]) among patients taking DOAC and amiodarone versus DOAC without amiodarone. Conclusion: On the basis of the results of this meta-analysis, co-administration of DOACs and amiodarone, a dual P-gp/CYP3A4 inhibitor, does not seem to affect efficacy or safety outcomes in patients with atrial fibrillation.

Original languageEnglish (US)
JournalAmerican Journal of Medicine
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Amiodarone
Anticoagulants
Atrial Fibrillation
Safety
P-Glycoprotein
Embolism
Odds Ratio
Hemorrhage
Stroke
Cytochrome P-450 CYP3A
Warfarin
Cytochromes
Drug Interactions
MEDLINE
Oral Administration
Meta-Analysis
Randomized Controlled Trials
Clinical Trials
Confidence Intervals

Keywords

  • Amiodarone
  • Atrial fibrillation
  • Cytochrome p450
  • Direct oral anticoagulants
  • Intracranial bleeding
  • Major bleeding events
  • P-glycoprotein
  • Stroke

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{286c9bb398ca482b9de0e61fdd0b6f02,
title = "Efficacy and Safety Outcomes of Direct Oral Anticoagulants and Amiodarone in Patients with Atrial Fibrillation",
abstract = "Background: Direct oral anticoagulants (DOACs) and amiodarone are widely used in the treatment of nonvalvular atrial fibrillation. The DOACs are P-glycoprotein (P-gp) and cytochrome p-450 (CYP3A4) substrates. Direct oral anticoagulant levels may be increased by the concomitant use of potent dual P-gp/CYP3A4 inhibitors, such as amiodarone, which can potentially translate into adverse clinical outcomes. We aimed to assess the efficacy and safety of drug-drug interaction by the concomitant use of DOACs and amiodarone. Methods: We performed a systematic review of MEDLINE, the Cochrane Central Register of Clinical Trials, and Embase, limiting our search to randomized controlled trials of patients with atrial fibrillation that have compared DOACs versus warfarin for prophylaxis of stroke or systemic embolism, to analyze the impact on stroke or systemic embolism, major bleeding, and intracranial bleeding risk in patients with concomitant use of amiodarone. Risk ratio (RR) 95{\%} confidence intervals were measured using the Mantel-Haenszel method. The fixed effects model was used owing to heterogeneity (I 2) < 25{\%}. Results: Four trials with a total of 71,683 patients were analyzed, from which 5{\%} of patients (n = 3212) were concomitantly taking DOAC and amiodarone. We found no statistically significant difference for any of the clinical outcomes (stroke or systemic embolism [RR 0.85; 95{\%} CI, 0.67-1.06], major bleeding [RR 0.91; 95{\%} CI, 0.77-1.07], or intracranial bleeding [RR 1.10; 95{\%} CI, 0.68-1.78]) among patients taking DOAC and amiodarone versus DOAC without amiodarone. Conclusion: On the basis of the results of this meta-analysis, co-administration of DOACs and amiodarone, a dual P-gp/CYP3A4 inhibitor, does not seem to affect efficacy or safety outcomes in patients with atrial fibrillation.",
keywords = "Amiodarone, Atrial fibrillation, Cytochrome p450, Direct oral anticoagulants, Intracranial bleeding, Major bleeding events, P-glycoprotein, Stroke",
author = "Florentino Lupercio and Romero, {Jorge E.} and Bradley Peltzer and Carola Maraboto and David Briceno and Pedro Villablanca and Ferrick, {Kevin J.} and Gross, {Jay N.} and Kim, {Soo G.} and Fisher, {John Devens} and {Di Biase}, Luigi and Krumerman, {Andrew K.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.amjmed.2017.11.047",
language = "English (US)",
journal = "American Journal of Medicine",
issn = "0002-9343",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Efficacy and Safety Outcomes of Direct Oral Anticoagulants and Amiodarone in Patients with Atrial Fibrillation

AU - Lupercio, Florentino

AU - Romero, Jorge E.

AU - Peltzer, Bradley

AU - Maraboto, Carola

AU - Briceno, David

AU - Villablanca, Pedro

AU - Ferrick, Kevin J.

AU - Gross, Jay N.

AU - Kim, Soo G.

AU - Fisher, John Devens

AU - Di Biase, Luigi

AU - Krumerman, Andrew K.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Direct oral anticoagulants (DOACs) and amiodarone are widely used in the treatment of nonvalvular atrial fibrillation. The DOACs are P-glycoprotein (P-gp) and cytochrome p-450 (CYP3A4) substrates. Direct oral anticoagulant levels may be increased by the concomitant use of potent dual P-gp/CYP3A4 inhibitors, such as amiodarone, which can potentially translate into adverse clinical outcomes. We aimed to assess the efficacy and safety of drug-drug interaction by the concomitant use of DOACs and amiodarone. Methods: We performed a systematic review of MEDLINE, the Cochrane Central Register of Clinical Trials, and Embase, limiting our search to randomized controlled trials of patients with atrial fibrillation that have compared DOACs versus warfarin for prophylaxis of stroke or systemic embolism, to analyze the impact on stroke or systemic embolism, major bleeding, and intracranial bleeding risk in patients with concomitant use of amiodarone. Risk ratio (RR) 95% confidence intervals were measured using the Mantel-Haenszel method. The fixed effects model was used owing to heterogeneity (I 2) < 25%. Results: Four trials with a total of 71,683 patients were analyzed, from which 5% of patients (n = 3212) were concomitantly taking DOAC and amiodarone. We found no statistically significant difference for any of the clinical outcomes (stroke or systemic embolism [RR 0.85; 95% CI, 0.67-1.06], major bleeding [RR 0.91; 95% CI, 0.77-1.07], or intracranial bleeding [RR 1.10; 95% CI, 0.68-1.78]) among patients taking DOAC and amiodarone versus DOAC without amiodarone. Conclusion: On the basis of the results of this meta-analysis, co-administration of DOACs and amiodarone, a dual P-gp/CYP3A4 inhibitor, does not seem to affect efficacy or safety outcomes in patients with atrial fibrillation.

AB - Background: Direct oral anticoagulants (DOACs) and amiodarone are widely used in the treatment of nonvalvular atrial fibrillation. The DOACs are P-glycoprotein (P-gp) and cytochrome p-450 (CYP3A4) substrates. Direct oral anticoagulant levels may be increased by the concomitant use of potent dual P-gp/CYP3A4 inhibitors, such as amiodarone, which can potentially translate into adverse clinical outcomes. We aimed to assess the efficacy and safety of drug-drug interaction by the concomitant use of DOACs and amiodarone. Methods: We performed a systematic review of MEDLINE, the Cochrane Central Register of Clinical Trials, and Embase, limiting our search to randomized controlled trials of patients with atrial fibrillation that have compared DOACs versus warfarin for prophylaxis of stroke or systemic embolism, to analyze the impact on stroke or systemic embolism, major bleeding, and intracranial bleeding risk in patients with concomitant use of amiodarone. Risk ratio (RR) 95% confidence intervals were measured using the Mantel-Haenszel method. The fixed effects model was used owing to heterogeneity (I 2) < 25%. Results: Four trials with a total of 71,683 patients were analyzed, from which 5% of patients (n = 3212) were concomitantly taking DOAC and amiodarone. We found no statistically significant difference for any of the clinical outcomes (stroke or systemic embolism [RR 0.85; 95% CI, 0.67-1.06], major bleeding [RR 0.91; 95% CI, 0.77-1.07], or intracranial bleeding [RR 1.10; 95% CI, 0.68-1.78]) among patients taking DOAC and amiodarone versus DOAC without amiodarone. Conclusion: On the basis of the results of this meta-analysis, co-administration of DOACs and amiodarone, a dual P-gp/CYP3A4 inhibitor, does not seem to affect efficacy or safety outcomes in patients with atrial fibrillation.

KW - Amiodarone

KW - Atrial fibrillation

KW - Cytochrome p450

KW - Direct oral anticoagulants

KW - Intracranial bleeding

KW - Major bleeding events

KW - P-glycoprotein

KW - Stroke

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U2 - 10.1016/j.amjmed.2017.11.047

DO - 10.1016/j.amjmed.2017.11.047

M3 - Article

JO - American Journal of Medicine

JF - American Journal of Medicine

SN - 0002-9343

ER -