Pascal Vranckx1, Marco Valgimigli2, Lars Eckardt3, Jan Tijssen4, Thorsten Lewalter5, Giuseppe Gargiulo6, Valerii Batushkin7, Gianluca Campo8, Zoreslava Lysak9, Igor Vakaliuk10, Krzysztof Milewski11, Petra Laeis12, Paul-Egbert Reimitz12, Rüdiger Smolnik12, Wolfgang Zierhut12, Andreas Goette13. 1. Department of Cardiology and Intensive Care, Jessa Ziekenhuis, Faculty of Medicine and Life Sciences at the Hasselt University, Hasselt, Belgium. Electronic address: pascal.vranckx@jessazh.be. 2. Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 3. Atrial Fibrillation Network, Munster, Germany; Department of Cardiology and Angiology, Division of Electrophysiology, University of Munster, Munster, Germany. 4. Department of Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands; Cardialysis, Rotterdam, Netherlands. 5. Atrial Fibrillation Network, Munster, Germany; Department of Cardiology, Hospital Munich South, Munich, Germany; University of Bonn, Bonn, Germany. 6. Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy. 7. Department of Cardiology, Kyiv City Clinical Hospital #5, Kiev, Ukraine. 8. Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona, Venice, Italy; Maria Cecilia Hospital, GVM Care and Research, Cotignola, Italy. 9. Department of Cardiac Rehabilitation, Oleksandrivska Kyiv City Clinical Hospital, Kiev, Ukraine. 10. Department Internal Medicine No2 and Nursing, Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine; Department of Anesthesiology with Wards of Intensive Care, Ivano-Frankivsk Regional Clinical Cardiological Clinic, Ivano-Frankivsk, Ukraine. 11. Center for Cardiovascular Research and Development, American Heart of Poland Katowice, Poland; The Jerzy Kukuczka Academy of Physical Education, Faculty of Physiotherapy, Katowice, Katowice, Poland. 12. Daiichi Sankyo Europe, Munich, Germany. 13. Atrial Fibrillation Network, Munster, Germany; Cardiology and Intensive Care Medicine, St Vincenz-Hospital, Paderborn, Germany; Working Group of Molecular Electrophysiology, University Hospital Magdeburg, Magdeburg, Germany. Electronic address: andreas.goette@vincenz.de.
Abstract
BACKGROUND: We aimed to assess the safety of edoxaban in combination with P2Y12 inhibition in patients with atrial fibrillation who had percutaneous coronary intervention (PCI). METHODS: ENTRUST-AF PCI was a randomised, multicentre, open-label, non-inferiority phase 3b trial with masked outcome evaluation, done at 186 sites in 18 countries. Patients had atrial fibrillation requiring oral anticoagulation, were aged at least 18 years, and had a successful PCI for stable coronary artery disease or acute coronary syndrome. Participants were randomly assigned (1:1) from 4 h to 5 days after PCI using concealed, stratified, and blocked web-based central randomisation to either edoxaban (60 mg once daily) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist (VKA) in combination with a P2Y12 inhibitor and aspirin (100 mg once daily, for 1-12 months). The edoxaban dose was reduced to 30 mg per day if one or more factors (creatinine clearance 15-50 mL/min, bodyweight ≤60 kg, or concomitant use of specified potent P-glycoprotein inhibitors) were present. The primary endpoint was a composite of major or clinically relevant non-major (CRNM) bleeding within 12 months. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of their assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02866175, is closed to new participants, and follow-up is completed. FINDINGS:From Feb 24, 2017, through May 7, 2018, 1506 patients were enrolled and randomly assigned to the edoxaban regimen (n=751) or VKA regimen (n=755). Median time from PCI to randomisation was 45·1 h (IQR 22·2-76·2). Major or CRNM bleeding events occurred in 128 (17%) of 751 patients (annualised event rate 20·7%) with the edoxaban regimen and 152 (20%) of 755 patients (annualised event rate 25·6%) patients with the VKA regimen; hazard ratio 0·83 (95% CI 0·65-1·05; p=0·0010 for non-inferiority, margin hazard ratio 1·20; p=0·1154 for superiority). INTERPRETATION: In patients with atrial fibrillation who had PCI, theedoxaban-based regimen was non-inferior for bleeding compared with the VKA-based regimen, without significant differences in ischaemic events. FUNDING: Daiichi Sankyo.
RCT Entities:
BACKGROUND: We aimed to assess the safety of edoxaban in combination with P2Y12 inhibition in patients with atrial fibrillation who had percutaneous coronary intervention (PCI). METHODS: ENTRUST-AF PCI was a randomised, multicentre, open-label, non-inferiority phase 3b trial with masked outcome evaluation, done at 186 sites in 18 countries. Patients had atrial fibrillation requiring oral anticoagulation, were aged at least 18 years, and had a successful PCI for stable coronary artery disease or acute coronary syndrome. Participants were randomly assigned (1:1) from 4 h to 5 days after PCI using concealed, stratified, and blocked web-based central randomisation to either edoxaban (60 mg once daily) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist (VKA) in combination with a P2Y12 inhibitor and aspirin (100 mg once daily, for 1-12 months). The edoxaban dose was reduced to 30 mg per day if one or more factors (creatinine clearance 15-50 mL/min, bodyweight ≤60 kg, or concomitant use of specified potent P-glycoprotein inhibitors) were present. The primary endpoint was a composite of major or clinically relevant non-major (CRNM) bleeding within 12 months. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of their assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02866175, is closed to new participants, and follow-up is completed. FINDINGS: From Feb 24, 2017, through May 7, 2018, 1506 patients were enrolled and randomly assigned to the edoxaban regimen (n=751) or VKA regimen (n=755). Median time from PCI to randomisation was 45·1 h (IQR 22·2-76·2). Major or CRNM bleeding events occurred in 128 (17%) of 751 patients (annualised event rate 20·7%) with the edoxaban regimen and 152 (20%) of 755 patients (annualised event rate 25·6%) patients with the VKA regimen; hazard ratio 0·83 (95% CI 0·65-1·05; p=0·0010 for non-inferiority, margin hazard ratio 1·20; p=0·1154 for superiority). INTERPRETATION: In patients with atrial fibrillation who had PCI, the edoxaban-based regimen was non-inferior for bleeding compared with the VKA-based regimen, without significant differences in ischaemic events. FUNDING: Daiichi Sankyo.
Authors: Safi U Khan; Mohammed Osman; Muhammad U Khan; Muhammad Shahzeb Khan; Di Zhao; Mamas A Mamas; Nazir Savji; Ahmad Al-Abdouh; Rani K Hasan; Erin D Michos Journal: Ann Intern Med Date: 2020-03-17 Impact factor: 25.391