Abstract
Aims
In ENSURE-AF (NCT02072434), the oral Factor Xa inhibitor edoxaban showed similar efficacy and safety vs enoxaparin–warfarin in patients undergoing electrical cardioversion of nonvalvular atrial fibrillation (AF). This ancillary analysis compares primary efficacy and safety end points for patients receiving vs not receiving concomitant antiplatelet therapy (APT) in ENSURE-AF.
Methods
The primary efficacy end point was a composite of stroke, systemic embolic events, myocardial infarction, and cardiovascular death during 28 days on study drug after cardioversion plus 30 days of follow-up. The primary safety end point was the composite of major and clinically relevant non-major bleeding occurring between the first and the last dose of study drug.
Results
Of 2199 patients enrolled, 1095 were randomized to edoxaban and 1104 to enoxaparin–warfarin. Patients receiving concomitant APT were older; more naïve to vitamin K antagonist; had lower creatinine clearance; and more likely to have history of coronary artery disease, hypertension, diabetes, or ischemic stroke/transient ischemic attack. In patients receiving vs not receiving concomitant APT, primary efficacy event rate was numerically higher (0.92% vs 0.60%, p = 0.64) and primary safety event rate was significantly higher (3.21% vs 0.92%, p = 0.0096). Stepwise logistic regression analysis identified age and APT as covariates correlated with bleeding. There was a trend toward increased bleeding risk in elderly patients receiving vs not receiving concomitant APT.
Conclusion
In ENSURE-AF, thromboembolic events were rare and absolute bleeding event rates were higher with concomitant APT. These findings may be relevant for AF-patients considered for dual therapy; even for a short treatment duration of 1 month.
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Acknowledgements
The ENSURE-AF study was sponsored and funded by Daiichi Sankyo, Inc.
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Andreas Goette, MD, has served as a consultant for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer; and a speaker for AstraZeneca, Bayer, Berlin-Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Pfizer, and Sanofi-Aventis. Jose L. Merino, MD, has served on the Speakers Bureau for Cardiome, Daiichi Sankyo, Medtronic, and St. Jude Medical; and has served as a consultant for Bayer, Biotronik, Boston Scientific, Bristol-Myers Squibb, Cardiome, Daiichi Sankyo, LivaNova, Medtronic, Pfizer, Sanofi, and St. Jude Medical. Raffaele De Caterina, MD, has received research grants from Pfizer, Daiichi Sankyo, Novartis, Merck Sharp, and Dohme; and has received honoraria from Sanofi, Boehringer-Ingelheim, Bayer, Bristol-Myers Squibb, Pfizer, and Portola. Kurt Huber, MD, has received lecture fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. Hein Heidbuchel, MD, has served as a consultant or speaker for Boehringer-Ingelheim, Bayer, Bristol-Myers Squibb, Cardiome, Daiichi-Sankyo, Pfizer, and St. Jude Medical. James Jin, PhD, is an employee of Daiichi Sankyo Pharma Development. Gregory Y.H. Lip, MD, has served as a consultant for Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Novartis, and Verseon; and a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Medtronic. No fees were directly received personally.
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Goette, A., Merino, J.L., De Caterina, R. et al. Effect of concomitant antiplatelet agents on clinical outcomes in the edoxaban vs warfarin in subjects undergoing cardioversion of atrial fibrillation (ENSURE-AF) randomized trial. Clin Res Cardiol 109, 1374–1380 (2020). https://doi.org/10.1007/s00392-020-01635-8
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DOI: https://doi.org/10.1007/s00392-020-01635-8