ORIGINAL R ESEARCH AR TICLE
The Peri-procedural Use of Dabigatran in Patients Undergoing Left Atrial Ablation for Atrial Fibrillation Riyaz Somani, Kiarash Mohajer, Charlotte Haley, Christopher S. Simpson, Hoshiar Abdollah, Adrian Baranchuk, Damian P. Redfearn & Kevin Michael Queen’s University, Kingston General Hospital, Kingston, ON, Canada
Keywords Atrial fibrillation; Dabigatran; pulmonary veinisolation; Warfarin. Correspondence A. Baranchuk, MD, FACC, FRCPC, Queen’s University, Kingston General Hospital, 76 Stuart St, FAPC Level 3, Kingston, ON, Canada K7L 2V7. Tel.: 613-549-6666 Ext 3377; Fax: 613-548-1387; E-mail: [email protected]
doi: 10.1111/1755-5922.12082
SUMMARY Introduction: Pulmonary vein isolation is an effective strategy in patients with atrial fibrillation (AF). The peri-procedural use of anticoagulation is routinely employed to reduce thromboembolic risk. Aims/Methods: The aim of this study was to compare the use of Dabigatran to the other 2 strategies involving the use of Warfarin. Single centre observational study comparing 3 anticoagulation strategies: Group 1 consisted of patients maintained on Warfarin (5.15 2.52 mg) with a therapeutic INR of 2–3. Group 2 comprised patients initially treated with Warfarin (6.98 3.17 mg), which was discontinued 1 week prior to LA ablation, during which time patients were bridged with a therapeutic dose of Dalteparin. Group 3 included patients anticoagulated with Dabigatran (40 patients received 150 mg BID, 3 patients received 110 mg BID), which was discontinued 24–30 h prior to the procedure. Results: A total of 207 patients were included in the study. There were no significant differences in age, sex, LA volume, CHADS2 score or proportion of patients with persistent AF. There were no significant differences in the number of patients with intra-cardiac thrombus found at TOE (Group 1: 2.3% vs. Group 2: 1.5% vs. Group 3: 0%; P = 0.37). Furthermore, there were no differences in the rate of groin hematoma (2.2% vs. 1.5% vs. 2.3%; P = 0.8) or the development of pericardial effusion (5.4% vs. 8.8% vs. 2.3%; P = 0.54). No thromboembolic events were seen. Conclusion: Peri-procedural use of Dabigatran during AF ablation procedures is safe, with no significant difference when compared to conventional anticoagulation with either Warfarin bridged with Dalteparin or uninterrupted Warfarin.
Introduction Atrial fibrillation (AF) is associated with significant thromboembolic risk. Several novel oral anticoagulants (NOACs) are now available and approved for stroke risk reduction [1,2]. Radiofrequency ablation (RFA) is increasingly being employed as an effective means of treating symptomatic patients with AF [3]. Patients undergoing RFA for AF are typically managed with oral anticoagulation before and after the procedure with widespread recognition that anticoagulation with heparin during the procedure itself further reduces stroke risk [3]. However, the peri-procedural management of oral anticoagulants has varied widely from center to center with some continuing oral anticoagulation with warfarin throughout, whilst others have used a strategy where oral anticoagulation is temporarily discontinued and substituted with either intravenous unfractionated heparin or subcutaneous low molecular weight heparin (LMWH) immediately before and after RFA, in a bid to minimize bleeding complications [4]. As the NOACs become more widely used, an increasing number of patients presenting for RFA of AF are likely to be taking Dabigatran, although its peri-procedural manage-
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Cardiovascular Therapeutics 32 (2014) 198–201
ment remains uncertain. We sought to evaluate the peri-procedural safety and efficacy of Dabigatran in patients undergoing RFA for both paroxysmal and persistent AF compared with patients receiving continuous Warfarin or interrupted Warfarin bridged with LMWH.
Methods All patients undergoing RFA for either paroxysmal or persistent nonvalvular AF at Queen’s University, Kingston, Ontario between November 1, 2010 and January 5, 2012 were included in this retrospective analysis. All patients underwent a transesophageal echocardiogram (TEE) prior to RFA.
Study Protocol 1 Continuous Warfarin group: Patients were maintained on Warfarin for ≥4 weeks before the procedure, with a documented therapeutic INR (2.0–3.0). Warfarin was continued throughout the peri-procedural period with INR levels measured on the day of the procedure.
ª 2014 John Wiley & Sons Ltd
R. Somani et al.
2 Interrupted Warfarin Group: Patients received Warfarin for ≥4 weeks before the procedure, with a documented therapeutic INR (2.0–3.0). Warfarin was discontinued 1 week prior to the procedure and substituted with the LMWH while Dalteparin was given subcutaneously (100 mg/kg/dose) every 12 hours. Patients with an estimated GFR, 50 mL/minute were excluded from this anticoagulation arm or considered for an adjusted dose of Dalteparin at the discretion of the physician. The last dose of Dalteparin was given 24–30 h prior to the procedure (and was recommenced 4 h after vascular hemostasis was achieved following sheath removal at half the total calculated dose initially and the full dose was administered 12 h later. Warfarin was recommenced at 1.5 times the patient’s usual dose in combination with Dalteparin until a therapeutic INR was reached. 3 Dabigatran group: Patients were commenced on Dabigatran 150 mg po bid (110 mg bid in three patients due to renal impairment) for ≥4 weeks before the procedure and were instructed to stop taking the drug the day before the procedure (24–30 h preprocedure). Dabigatran was resumed 4–6 h after vascular hemostasis was achieved following sheath removal. All patients remained on oral anticoagulation for a minimum of 3 months after the procedure.
Ablation Procedure RFA was performed by one of three operators in the fasting state under moderate or deep sedation using fentanyl sodium and midazolam. Two 7 F and two 12 F hemostatic sheaths were placed into one or both femoral veins using a modified Seldinger technique. Through the 7 F sheaths, a decapolar catheter was advanced to the coronary sinus (CS) and a quadripolar catheter was advanced to the right ventricular (RV) apex. Through a 12 F sheath, a transseptal sheath (SL1; St. Jude Medical, Minneapolis, MN, USA) housing a Brockenbrough needle was introduced to gain access to the LA under fluoroscopic guidance. A guide wire was then advanced through the transseptal sheath into the leftsided pulmonary vein and the sheath was then brought back into the RA. A 4 mm irrigated ablation catheter (St. Jude Medical) was introduced into a 2nd transseptal sheath and advanced through the 12 F sheath into the right atrium (RA). The ablation catheter was then passed into the LA alongside the guidewire with both transseptal sheaths then re-advanced into the LA. Intracardiac echocardiography (ICE) was not routinely performed. Unfractionated heparin was administered intravenously after both sheaths were successfully introduced into the LA with an initial dose of 100 units/Kg. The activated clotting time (ACT) was measured from venous blood at 10–20 min intervals with a target ACT of 250–300 seconds in the continuous Warfarin group and a target of 300–350 seconds for patients in the other two groups. A circular mapping catheter (Reflexion; St. Jude Medical) was advanced through the transseptal sheath and placed in the ostia of all pulmonary veins. The LA was mapped using the velocity (St. Jude Medical) mapping system. The pulmonary veins were then anatomically encircled and electrically isolated using RFA with powers of 25–30 W. Ablation was continued until entrance
ª 2014 John Wiley & Sons Ltd
Dabigatran During Left Atrial Ablation
and exit block were achieved between the pulmonary veins and the left atrium. In patients with paroxysmal AF, circumferential pulmonary vein isolation (CPVI) alone was performed. In patients with persistent AF, additional substrate modification was performed, including ablation of complex fractionated atrial electrograms (CFAE) and linear ablation tailored to each individual patient. Following completion of ablation, all catheters were removed from the body in a specialized nursing unit when the ACT had declined to
The Peri-procedural Use of Dabigatran in Patients Undergoing Left Atrial Ablation for Atrial Fibrillation Riyaz Somani, Kiarash Mohajer, Charlotte Haley, Christopher S. Simpson, Hoshiar Abdollah, Adrian Baranchuk, Damian P. Redfearn & Kevin Michael Queen’s University, Kingston General Hospital, Kingston, ON, Canada
Keywords Atrial fibrillation; Dabigatran; pulmonary veinisolation; Warfarin. Correspondence A. Baranchuk, MD, FACC, FRCPC, Queen’s University, Kingston General Hospital, 76 Stuart St, FAPC Level 3, Kingston, ON, Canada K7L 2V7. Tel.: 613-549-6666 Ext 3377; Fax: 613-548-1387; E-mail: [email protected]
doi: 10.1111/1755-5922.12082
SUMMARY Introduction: Pulmonary vein isolation is an effective strategy in patients with atrial fibrillation (AF). The peri-procedural use of anticoagulation is routinely employed to reduce thromboembolic risk. Aims/Methods: The aim of this study was to compare the use of Dabigatran to the other 2 strategies involving the use of Warfarin. Single centre observational study comparing 3 anticoagulation strategies: Group 1 consisted of patients maintained on Warfarin (5.15 2.52 mg) with a therapeutic INR of 2–3. Group 2 comprised patients initially treated with Warfarin (6.98 3.17 mg), which was discontinued 1 week prior to LA ablation, during which time patients were bridged with a therapeutic dose of Dalteparin. Group 3 included patients anticoagulated with Dabigatran (40 patients received 150 mg BID, 3 patients received 110 mg BID), which was discontinued 24–30 h prior to the procedure. Results: A total of 207 patients were included in the study. There were no significant differences in age, sex, LA volume, CHADS2 score or proportion of patients with persistent AF. There were no significant differences in the number of patients with intra-cardiac thrombus found at TOE (Group 1: 2.3% vs. Group 2: 1.5% vs. Group 3: 0%; P = 0.37). Furthermore, there were no differences in the rate of groin hematoma (2.2% vs. 1.5% vs. 2.3%; P = 0.8) or the development of pericardial effusion (5.4% vs. 8.8% vs. 2.3%; P = 0.54). No thromboembolic events were seen. Conclusion: Peri-procedural use of Dabigatran during AF ablation procedures is safe, with no significant difference when compared to conventional anticoagulation with either Warfarin bridged with Dalteparin or uninterrupted Warfarin.
Introduction Atrial fibrillation (AF) is associated with significant thromboembolic risk. Several novel oral anticoagulants (NOACs) are now available and approved for stroke risk reduction [1,2]. Radiofrequency ablation (RFA) is increasingly being employed as an effective means of treating symptomatic patients with AF [3]. Patients undergoing RFA for AF are typically managed with oral anticoagulation before and after the procedure with widespread recognition that anticoagulation with heparin during the procedure itself further reduces stroke risk [3]. However, the peri-procedural management of oral anticoagulants has varied widely from center to center with some continuing oral anticoagulation with warfarin throughout, whilst others have used a strategy where oral anticoagulation is temporarily discontinued and substituted with either intravenous unfractionated heparin or subcutaneous low molecular weight heparin (LMWH) immediately before and after RFA, in a bid to minimize bleeding complications [4]. As the NOACs become more widely used, an increasing number of patients presenting for RFA of AF are likely to be taking Dabigatran, although its peri-procedural manage-
198
Cardiovascular Therapeutics 32 (2014) 198–201
ment remains uncertain. We sought to evaluate the peri-procedural safety and efficacy of Dabigatran in patients undergoing RFA for both paroxysmal and persistent AF compared with patients receiving continuous Warfarin or interrupted Warfarin bridged with LMWH.
Methods All patients undergoing RFA for either paroxysmal or persistent nonvalvular AF at Queen’s University, Kingston, Ontario between November 1, 2010 and January 5, 2012 were included in this retrospective analysis. All patients underwent a transesophageal echocardiogram (TEE) prior to RFA.
Study Protocol 1 Continuous Warfarin group: Patients were maintained on Warfarin for ≥4 weeks before the procedure, with a documented therapeutic INR (2.0–3.0). Warfarin was continued throughout the peri-procedural period with INR levels measured on the day of the procedure.
ª 2014 John Wiley & Sons Ltd
R. Somani et al.
2 Interrupted Warfarin Group: Patients received Warfarin for ≥4 weeks before the procedure, with a documented therapeutic INR (2.0–3.0). Warfarin was discontinued 1 week prior to the procedure and substituted with the LMWH while Dalteparin was given subcutaneously (100 mg/kg/dose) every 12 hours. Patients with an estimated GFR, 50 mL/minute were excluded from this anticoagulation arm or considered for an adjusted dose of Dalteparin at the discretion of the physician. The last dose of Dalteparin was given 24–30 h prior to the procedure (and was recommenced 4 h after vascular hemostasis was achieved following sheath removal at half the total calculated dose initially and the full dose was administered 12 h later. Warfarin was recommenced at 1.5 times the patient’s usual dose in combination with Dalteparin until a therapeutic INR was reached. 3 Dabigatran group: Patients were commenced on Dabigatran 150 mg po bid (110 mg bid in three patients due to renal impairment) for ≥4 weeks before the procedure and were instructed to stop taking the drug the day before the procedure (24–30 h preprocedure). Dabigatran was resumed 4–6 h after vascular hemostasis was achieved following sheath removal. All patients remained on oral anticoagulation for a minimum of 3 months after the procedure.
Ablation Procedure RFA was performed by one of three operators in the fasting state under moderate or deep sedation using fentanyl sodium and midazolam. Two 7 F and two 12 F hemostatic sheaths were placed into one or both femoral veins using a modified Seldinger technique. Through the 7 F sheaths, a decapolar catheter was advanced to the coronary sinus (CS) and a quadripolar catheter was advanced to the right ventricular (RV) apex. Through a 12 F sheath, a transseptal sheath (SL1; St. Jude Medical, Minneapolis, MN, USA) housing a Brockenbrough needle was introduced to gain access to the LA under fluoroscopic guidance. A guide wire was then advanced through the transseptal sheath into the leftsided pulmonary vein and the sheath was then brought back into the RA. A 4 mm irrigated ablation catheter (St. Jude Medical) was introduced into a 2nd transseptal sheath and advanced through the 12 F sheath into the right atrium (RA). The ablation catheter was then passed into the LA alongside the guidewire with both transseptal sheaths then re-advanced into the LA. Intracardiac echocardiography (ICE) was not routinely performed. Unfractionated heparin was administered intravenously after both sheaths were successfully introduced into the LA with an initial dose of 100 units/Kg. The activated clotting time (ACT) was measured from venous blood at 10–20 min intervals with a target ACT of 250–300 seconds in the continuous Warfarin group and a target of 300–350 seconds for patients in the other two groups. A circular mapping catheter (Reflexion; St. Jude Medical) was advanced through the transseptal sheath and placed in the ostia of all pulmonary veins. The LA was mapped using the velocity (St. Jude Medical) mapping system. The pulmonary veins were then anatomically encircled and electrically isolated using RFA with powers of 25–30 W. Ablation was continued until entrance
ª 2014 John Wiley & Sons Ltd
Dabigatran During Left Atrial Ablation
and exit block were achieved between the pulmonary veins and the left atrium. In patients with paroxysmal AF, circumferential pulmonary vein isolation (CPVI) alone was performed. In patients with persistent AF, additional substrate modification was performed, including ablation of complex fractionated atrial electrograms (CFAE) and linear ablation tailored to each individual patient. Following completion of ablation, all catheters were removed from the body in a specialized nursing unit when the ACT had declined to
