Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation.
Catheter ablation of atrial fibrillation is typically performed with uninterrupted anticoagulation with warfarin or interrupted non-vitamin K antagonist oral anticoagulant therapy. Uninterrupted anticoagulation with a non-vitamin K antagonist oral anticoagulant, such as dabigatran, may be safer; however, controlled data are lacking. We investigated the safety of uninterrupted dabigatran versus warfarin in patients undergoing ablation of atrial fibrillation.



In this randomized, open-label, multicenter, controlled trial with blinded adjudicated end-point assessments, we randomly assigned patients scheduled for catheter ablation of paroxysmal or persistent atrial fibrillation to receive either dabigatran (150 mg twice daily) or warfarin (target international normalized ratio, 2.0 to 3.0). Ablation was performed after 4 to 8 weeks of uninterrupted anticoagulation, which was continued during and for 8 weeks after ablation. The primary end point was the incidence of major bleeding events during and up to 8 weeks after ablation; secondary end points included thromboembolic and other bleeding events.



The trial enrolled 704 patients across 104 sites; 635 patients underwent ablation. Baseline characteristics were balanced between treatment groups. The incidence of major bleeding events during and up to 8 weeks after ablation was lower with dabigatran than with warfarin (5 patients [1.6%] vs. 22 patients [6.9%]; absolute risk difference, -5.3 percentage points; 95% confidence interval, -8.4 to -2.2; P<0.001). Dabigatran was associated with fewer periprocedural pericardial tamponades and groin hematomas than warfarin. The two treatment groups had a similar incidence of minor bleeding events. One thromboembolic event occurred in the warfarin group.



In patients undergoing ablation for atrial fibrillation, anticoagulation with uninterrupted dabigatran was associated with fewer bleeding complications than uninterrupted warfarin. (Funded by Boehringer Ingelheim; RE-CIRCUIT ClinicalTrials.gov number, NCT02348723 .).
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology-Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) - all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew's Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) - both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.).
Hugh
H
Calkins
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology-Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) - all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew's Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) - both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.).
Stephan
S
Willems
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology-Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) - all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew's Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) - both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.).
Edward P
EP
Gerstenfeld
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology-Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) - all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew's Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) - both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.).
Atul
A
Verma
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology-Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) - all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew's Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) - both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.).
Richard
R
Schilling
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology-Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) - all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew's Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) - both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.).
Stefan H
SH
Hohnloser
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology-Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) - all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew's Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) - both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.).
Ken
K
Okumura
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology-Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) - all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew's Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) - both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.).
Harvey
H
Serota
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology-Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) - all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew's Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) - both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.).
Matias
M
Nordaby
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology-Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) - all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew's Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) - both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.).
Kelly
K
Guiver
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology-Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) - all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew's Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) - both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.).
Branislav
B
Biss
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology-Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) - all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew's Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) - both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.).
Marc A
MA
Brouwer
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology-Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) - all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew's Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) - both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.).
Massimo
M
Grimaldi
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000601:surgery*; D017115:Catheter Ablation; D000069604:Dabigatran / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000139:chemically induced / Q000453:epidemiology; D020521:Stroke / Q000517:prevention & control; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
D000925:Anticoagulants; D014859:Warfarin; D000069604:Dabigatran