Michael D Ezekowitz1, Charles V Pollack2, Paul Sanders3, Jonathan L Halperin4, Judith Spahr5, Nilo Cater6, William Petkun7, Andrei Breazna6, Paulus Kirchhof8, Jonas Oldgren9. 1. Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA; Lankenau Medical Center, Wynnewood, PA. Electronic address: michael.ezekowitz@comcast.net. 2. Thomas Jefferson University, Philadelphia, PA. 3. Pfizer, London, United Kingdom. 4. Icahn School of Medicine at Mount Sinai, New York, NY. 5. Lankenau Institute for Medical Research, Wynnewood, PA. 6. Pfizer, New York, NY. 7. Bristol-Myers-Squibb Inc, Princeton, NJ. 8. University of Birmingham Institute of Cardiovascular Sciences, SWBH UHB NHS trusts, Birmingham, United Kingdom; Department of Cardiology and Angiology, University Hospital Münster, Münster, Germany. 9. Uppsala Clinical Research Centre, and Dept. of Medical Sciences, Uppsala University, Uppsala, Sweden.
Abstract
BACKGROUND: Stroke prevention in anticoagulation-naïve patients with atrial fibrillation undergoing cardioversion has not been systematically studied. OBJECTIVE: To determine outcomes in anticoagulation-naïve patients (defined as those receiving an anticoagulant for <48 hours during the index episode of atrial fibrillation) scheduled for cardioversion. METHODS: This is a randomized, prospective, open-label, real-world study comparing apixaban to heparin plus warfarin. Early image-guided cardioversion is encouraged. For apixaban, the usual dose is 5 mg BID with a dose reduction to 2.5 mg BID if 2 of the following are present: age >80 years, weight <60 kg, or serum creatinine >1.5 mg/dL. If cardioversion is immediate, a single starting dose of 10 mg (or 5 mg if the dose is down-titrated) of apixaban is administered. Cardioversion may be attempted up to 90 days after randomization. Patients are followed up for 30 days after cardioversion or 90 days postrandomization if cardioversion is not performed within that timeframe. Outcomes are stroke, systemic embolization, major bleeds, clinically relevant nonmajor bleeding, and death, all adjudication-blinded. STATISTICS: The warfarin-naive cohort from the ARISTOTLE study was considered the closest data set to the patients being recruited into this study. The predicted incidence of stroke, systemic embolism, and major bleeding within 30 days after randomization was approximately 0.75%. To adequately power for a noninferiority trial, approximately 48,000 participants would be needed, a number in excess of feasibility. The figure of 1,500 patients was considered clinically meaningful and achievable. CLINICAL CONTEXT: This first prospective cardioversion study of a novel anticoagulant in anticoagulation-naïve patients should influence clinical practice.
BACKGROUND: Stroke prevention in anticoagulation-naïve patients with atrial fibrillation undergoing cardioversion has not been systematically studied. OBJECTIVE: To determine outcomes in anticoagulation-naïve patients (defined as those receiving an anticoagulant for <48 hours during the index episode of atrial fibrillation) scheduled for cardioversion. METHODS: This is a randomized, prospective, open-label, real-world study comparing apixaban to heparin plus warfarin. Early image-guided cardioversion is encouraged. For apixaban, the usual dose is 5 mg BID with a dose reduction to 2.5 mg BID if 2 of the following are present: age >80 years, weight <60 kg, or serum creatinine >1.5 mg/dL. If cardioversion is immediate, a single starting dose of 10 mg (or 5 mg if the dose is down-titrated) of apixaban is administered. Cardioversion may be attempted up to 90 days after randomization. Patients are followed up for 30 days after cardioversion or 90 days postrandomization if cardioversion is not performed within that timeframe. Outcomes are stroke, systemic embolization, major bleeds, clinically relevant nonmajor bleeding, and death, all adjudication-blinded. STATISTICS: The warfarin-naive cohort from the ARISTOTLE study was considered the closest data set to the patients being recruited into this study. The predicted incidence of stroke, systemic embolism, and major bleeding within 30 days after randomization was approximately 0.75%. To adequately power for a noninferiority trial, approximately 48,000 participants would be needed, a number in excess of feasibility. The figure of 1,500 patients was considered clinically meaningful and achievable. CLINICAL CONTEXT: This first prospective cardioversion study of a novel anticoagulant in anticoagulation-naïve patients should influence clinical practice.
Authors: Michael D Ezekowitz; Charles V Pollack; Jonathan L Halperin; Richard D England; Sandra VanPelt Nguyen; Judith Spahr; Maria Sudworth; Nilo B Cater; Andrei Breazna; Jonas Oldgren; Paulus Kirchhof Journal: Eur Heart J Date: 2018-08-21 Impact factor: 29.983
Authors: Jose L Merino; Gregory Y H Lip; Hein Heidbuchel; Aron-Ariel Cohen; Raffaele De Caterina; Joris R de Groot; Michael D Ezekowitz; Jean-Yves Le Heuzey; Sakis Themistoclakis; James Jin; Michael Melino; Shannon M Winters; Béla Merkely; Andreas Goette Journal: Europace Date: 2019-11-01 Impact factor: 5.214
Authors: Axel Brandes; Harry J G M Crijns; Michiel Rienstra; Paulus Kirchhof; Erik L Grove; Kenneth Bruun Pedersen; Isabelle C Van Gelder Journal: Europace Date: 2020-08-01 Impact factor: 5.214