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.
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References
- Atrial fibrillation–the growing epidemic.Heart. 2007; 93: 542-543
- Temporal trends in the incidence, prevalence, and survival of patients with atrial fibrillation from 2004 to 2016.Am J Cardiol. 2017; 120: 1961-1965
- Epidemiology of atrial fibrillation in the 21st Century: novel Methods and New Insights.Circ Res. 2020; 127: 4-20
- Trends and variation in oral anticoagulant choice in patients with atrial fibrillation, 2010–2017.Pharmacotherapy. 2018; 38: 907-920
- Risk of hospitalization with hemorrhage among older adults taking clarithromycin vs azithromycin and direct oral anticoagulants.JAMA Intern Med. 2020; 180: 1052-1060
- Old and new oral anticoagulants: food, herbal medicines and drug interactions.Blood Rev. 2017; 31: 193-203
- Safety and interactions of direct oral anticoagulants with antiarrhythmic drugs.Drug Saf. 2017; 40: 1091-1098
- Association between use of non-vitamin K oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation.JAMA. 2017; 318: 1250-1259
- Bleeding associated with coadministration of Rivaroxaban and clarithromycin.CMAJ. 2016; 188: 669-672
- Novel oral anticoagulants and HIV: dabigatran use with antiretrovirals.BMJ Case Rep. 2015; 2015
- Drug interactions with new oral anticoagulants in elderly patients.Expert Rev Clin Pharmacol. 2017; 10: 1191-1202
- Interactions between non-vitamin K oral anticoagulants and antiepileptic drugs.Epilepsy Res. 2016; 126: 98-101
- Drug-drug interactions of non-vitamin K oral anticoagulants.Expert Opin Drug Metab Toxicol. 2016; 12: 1445-1461
- Pharmacokinetic and pharmacodynamic drug interactions with new oral anticoagulants: what do they mean for patients with atrial fibrillation?.Ann Pharmacother. 2013; 47: 1478-1487
- Prescribing of two potentially interacting cardiovascular medications in atrial fibrillation patients on direct oral anticoagulants.Int J Cardiol Heart Vasc. 2021; 34100788
- Gopinathannair R, from the American Heart Association Electrocardiography and Arrhythmias Committee of the Council of Clinical Cardiology. Drug Interactions Affecting Antiarrhythmic Drug Use.Circ Arrhythm Electrophysiol. 2022; 15e007955
- The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.Eur Heart J. 2018; 39: 1330-1393
- Efficacy and safety of apixaban compared with warfarin for stroke prevention in patients with atrial fibrillation from East Asia: a subanalysis of the apixaban for Reduction in Stroke and Other thromboembolic events in atrial fibrillation (ARISTOTLE) trial.Am Heart J. 2014; 168: 303-309
- Dabigatran versus warfarin: effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation.Stroke. 2013; 44: 1891-1896
- Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation.J Am Coll Cardiol. 2007; 50: 309-315
- Rivaroxaban for stroke prevention in East Asian patients from the ROCKET AF trial.Stroke. 2014; 45: 1739-1747
Thrombosis Canada. Clinical Guides. Available at: http://thrombosiscanada.ca/clinicalguides/#. Accessed on July 15, 2021.
- Direct oral anticoagulant use: a practical guide to common clinical challenges.J Am Heart Assoc. 2020; 9e017559
- Emergency department volume and outcomes for patients after chest pain assessment.Circ Cardiovasc Qual Outcomes. 2018; 11e004683
- Identifying patients with atrial fibrillation in administrative data.Can J Cardiol. 2016; 32: 1561-1565
- Evidence-based analysis of amiodarone efficacy and safety.Circulation. 1999; 100: 2025-2034
- Prescribing amiodarone: an evidence-based review of clinical indications.JAMA. 2007; 298: 1312-1322
- Amiodarone kinetics after oral doses.Clin Pharmacol Ther. 1982; 31: 438-444
- Effectiveness of amiodarone for conversion of atrial fibrillation to sinus rhythm: a meta-analysis.Arch Intern Med. 2003; 163: 777-785
- RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation.N Engl J Med. 2009; 361: 1139-1151
- ARISTOTLE Committees and Investigators. Amiodarone, anticoagulation, and clinical events in patients with atrial fibrillation: insights from the ARISTOTLE trial.J Am Coll Cardiol. 2014; 64: 1541-1550
- Apixaban versus warfarin in patients with atrial fibrillation.N Engl J Med. 2011; 365: 981-992
- Drug-drug interactions among elderly patients hospitalized for drug toxicity.JAMA. 2003; 289: 1652-1658
- Practical considerations for the nonvitamin K antagonist oral anticoagulants.Cardiology. 2017; 136: 115-124
Article info
Publication history
Published online: November 04, 2022
Received in revised form:
October 4,
2022
Received:
September 13,
2022
Footnotes
Funding: This study was funded by a foundation grant (FDN-154333) from Canadian Institute for Health Information (Ottawa, Canada) and a Northern Ontario Academic Medicine Association (Thunder Bay, Canada) grant.
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