Major bleeding in patients with atrial fibrillation treated with apixaban versus warfarin in combination with amiodarone: nationwide cohort study.

Background: Amiodarone is an established treatment for atrial fibrillation (AF) but might interfere with the metabolism of apixaban or warfarin. Therefore, the aim was to investigate the occurrence of major bleeding among patients with AF treated with amiodarone in combination with apixaban or warfarin.

Methods: Retrospective observational study using Swedish health registers. All patients with AF in the National Patient Register and the National Dispensed Drug Register with concomitant use of amiodarone and warfarin or apixaban between 1 June 2013 and 31 December 2018 were included. Propensity score matching was performed, and matched cohorts were compared using Cox proportional HRs. The primary outcome was major bleeding resulting in hospitalisation based on International Classification of Diseases (ICD)-10 codes. Secondary outcomes included intracranial bleeding, gastrointestinal bleeding and other bleeding. Exploratory outcomes included ischaemic stroke/systemic embolism and all-cause/cardiovascular (CV) mortality.

Results: A total of 12 103 patients met the inclusion criteria and 8686 patients were included after propensity score matching. Rates of major bleeding were similar in the apixaban (4.3/100 patient-years) and warfarin cohort (4.5/100 patient-years) (HR: 1.03; 95% CI: 0.76 to 1.39) during median follow-up of 4.4 months. Similar findings were observed for secondary outcomes including gastrointestinal bleeding and other bleeding, and exploratory outcomes including ischaemic stroke/systemic embolism and all-cause/CV mortality.

Conclusions: Among patients treated with amiodarone in combination with apixaban or warfarin, major bleeding and thromboembolic events were rare and with no significant difference between the treatment groups.

Eupas Registry Number: EUPAS43681.

Competing Interests: Competing interests: AFH, nothing to declare. AM is an employee of Pfizer. HR, nothing to declare. CC reports speaker fees or advisory board from Bristol Myers Squibb, Bayer, Novartis, Orion Pharma, Amarin and AstraZeneca. Personal fees from event adjudication for Uppsala Clinical Research Center. CH reports institutional research grants from Pfizer, GlaxoSmith Kline, AstraZeneca, Bristol Myers Squibb, advisory board from AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk and Coala Life. Personal fees from event adjudication for Uppsala Clinical Research Center. GB reports institutional research grants from AstraZeneca and Pfizer, expert committee and consulting fees to his institution from Bayer. Honoraria for lectures and scientific advice from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Novo Nordisk, Pfizer and Sanofi.

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