Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation
Condition: Thromboembolism
MeSH terms: Atrial Fibrillation; Thromboembolism
Study type: Interventional
Phase: Phase 3

Summary: 
      This study aims to explore the risk of periprocedural thromboembolic events in continuous
      versus interrupted Coumadin therapy in a large, randomized high-risk patient population
      undergoing radio-frequency catheter ablation for atrial fibrillation.
    

Detailed description: 
      Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice,
      affecting 2.3 million people in the United States (1). A major cause of stroke, AF
      substantially increases the risk of thromboembolism which necessitates oral anticoagulation
      therapy (OAT) for high-risk patients. Radiofrequency percutaneous catheter ablation (RFCA) is
      an effective strategy for the treatment of symptomatic drug-refractory atrial fibrillation.
      However, periprocedural cerebrovascular accident (CVA) due to thrombus or air embolism
      remains one of the most serious complications of AF ablation. In spite of precautions taken
      before, during, and after the ablation to minimize the risk of CVA, the reported event rate
      remains 0.5-2.8% (2).

      The incidence of thromboembolic events is dependent on the extensiveness of the ablation
      procedure as well as the periprocedural anticoagulation strategy (2). Some studies have
      described charring and soft thrombus formation when the temperature exceeds 100 degree C
      during RFCA, which probably is caused by blood protein denaturation and coagulation (3).
      Currently an open saline irrigation-tip ablation catheter (3.5 mm Thermocool catheter) is
      used which reduces the thermal injury by keeping the temperature under control (4), while
      enabling the operator to use high wattage RF energy to effectively ablate the arrhythmogenic
      focus.

      The two most utilized periprocedural OAT strategies are; 1) discontinuation of Coumadin three
      to five days prior to ablation, utilization of heparin or enoxaparin before the procedures,
      and "bridging" low molecular weight heparin with Coumadin after ablation, and 2) RFCA with
      continuation of Coumadin before, during and after the procedure (2) without any change in
      dosage. Limited data are available regarding the risk of thromboembolism with and without
      periprocedural Coumadin in AF patients undergoing catheter ablation .The aim of this
      prospective randomized study is to evaluate the effect of the above two OAT strategies on the
      incidence of TE within 48 hours post-RFCA.

      Patient Selection, Treatment and Follow-up Period:

      Patients randomized as study group would continue Coumadin without any periprocedural change
      while undergoing catheter ablation. Those randomized as control group would discontinue
      Coumadin 3-4 days prior to ablation and replace it with heparin till the end of the procedure
      and bridge LMWH with Coumadin 48-72 hours after ablation.

      An INR of 2-3 would be ascertained in all patients prior to procedure. Patients with
      subtherapeutic INR would not be included in this study.

      Procedure: Coumadin therapy would be started at least two months prior to the ablation in
      order to achieve the therapeutic INR at least three weeks prior to the procedure.

      Anticoagulation strategy I (Coumadin interrupted): Twice daily until the evening prior to
      ablation procedure, 0.5-1 mg/kg of enoxaparin would be administered and bridged to Coumadin.
      At the time of the procedure, enoxaparin would be replaced by heparin. At the end of the
      procedure, the sheaths would be removed during full anticoagulation. After the procedure
      heparin would be discontinued, and protamine 10 to 15 mg would be given. Sheaths would be
      pulled when activated clotting time (ACT) would be <250 seconds. Aspirin 325 mg would be
      given before the patient leaves the electrophysiology laboratory. Warfarin would be
      administered the evening of pulmonary vein isolation. Enoxaparin 1 mg/kg BID and 0.5 mg/kg
      BID would be routinely started and would be stopped when the INR is > 2. Patients with LSPAF,
      left ventricular dysfunction or history of thrombo-embolism would receive overlapping
      anticoagulation with enoxaparin for three days after the procedure. The remaining patients
      would receive a double dose of Coumadin on the night of the ablation followed by the routine
      pre-procedure dose from the next day.

      Anticoagulation strategy II (continuous Coumadin): Coumadin would not be discontinued in this
      group of patients. The INR would be monitored every week for four weeks preceding the
      ablation and it should be above 2.0. All patients in AF on the day of the procedure where an
      INR above 2 is not demonstrable for four consecutive weeks preceding the procedure would
      undergo TEE.

      PVAI would be done while on Coumadin treatment. No heparin or enoxaparin would be
      administered to any patient prior to the procedure. Before transseptal punctures, a heparin
      bolus (100 to 150 U/Kg) would be administered to all patients. During the procedure, the
      infusion rate would be adjusted to keep the activated clotting time in the range of 350 to
      450 sec.

      After the procedures, heparin infusion would be stopped and anticoagulation would be reversed
      with 10 to 15 mg of Protamine, and sheaths would be pulled when the activated clotting time
      is less than 250 sec. Patients would receive 325 mg of Aspirin before leaving the EP lab.
      They would continue their Coumadin dosage regimens with no changes before or after the
      procedure aiming to an INR of 2 to 3.

      Following randomization, patients are considered to be in the treatment period 2 months
      before the procedure to 48-72 hours after the procedure.

      Ablation Procedure: Standard radiofrequency catheter ablation procedure based on physician's
      discretion would be followed.

      All patients will undergo baseline and post-procedure MRI within 24-hours of the procedure.

      Follow-up period is 48 hours post-procedure; during which all patients would have neurologic
      evaluation; at the end of the procedure and every four hours for the next 48 hours. Clinical
      neurologic evaluation would include assessment of mental status such as ability to pay
      attention, memory, judgment and orientation to self, place and time; maneuvers to test the
      cranial nerves, assessment of motor functions by testing strength in different muscle groups
      and assessment of sensory functions by evaluating touch, pain, vibration and positional
      awareness as well as the deep tendon reflexes.

      Patients with questionable neurologic impairment would undergo neuroimaging evaluations like
      head CT or MRI.
    

Intervention name(s): Coumadin; Coumadin; Coumadin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Continuous oral Coumadin therapy through the catheter ablation procedure; Patients discontinue Coumadin 3-4 days prior to ablation and replace it with heparin until the end of the procedure and bridge low molecular weight heparin (LMWH) with Coumadin 48-72 hours after ablation.; Oral tablets, daily dose, till the therapeutic INR of 2-3 is achieved
Other intervention name(s): warfarin; Warfarin; Warfarin
Intervention MeSH terms: Warfarin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: coumadin; peri-procedural thromboembolism; RFCA; high risk atrial fibrillation