Randomized Study of the Use of Warfarin During Pacemaker or ICD Implantation in Patients Requiring Long Term Anticoagulation

Study Overview
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Brief Summary
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Patients requiring long term anticoagulation often undergo transition of their warfarin to heparin in anticipation of invasive surgical procedures such as pacemaker or ICD implantation. This may require inpatient hospitalization several days prior to and after the procedure, potentially increasing medical costs and patient inconvenience. Patients undergoing such a process are initiated on heparin while their INRs drift to normal levels. Immediately prior to surgery, heparin is discontinued and restarted several hours after the procedure. Unfortunately, this process has resulted in a high incidence of surgical wound hematomas and other bleeding complications often requiring longer periods of discontinued anticoagulation or repeat surgical exploration. Previous investigators have tried to reduce the incidence of wound hematomas by prolonging the time from surgical wound closure to the reinitiation of heparin. A small randomized trial demonstrated that there was no significant difference in the incidence of wound hematomas whether heparin was started 6 hours or 24 hours after surgery (J Am Coll Cardiology 2000;35:1915-8). This has led many investigators to perform pacemaker and ICD implantation without reversal of warfarin therapy. A recent retrospective observational study demonstrated that the incidence of wound hematomas in patients with an INR of 2.6 was no different than patients with an INR of 1.5 (PACE 2004;27:358-60). Furthermore, a more recent, larger retrospective observational study reported in abstract form at the recent Heart Rhythm Society Annual 2007 Scientific Meeting demonstrated that not only is performing pacemaker and ICD implantations safe without reversing warfarin anticoagulation, but the incidence of wound hematomas is significantly smaller as compared to the strategy of reversing warfarin and initiating periprocedural heparin. Given these findings, the hypothesis of this randomized study is that pacemaker and ICD implantation while fully anticoagulated on warfarin therapy is safe. Findings from this study will have significant implications on the clinical practice of pacemaker or ICD implantation in this patient population given that no randomized study on this subject has been performed to date.

Official Title
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Randomized Study of the Use of Warfarin During Pacemaker or ICD Implantation in Patients Requiring Long Term Anticoagulation

Conditions
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Bradycardia, Tachycardia, Atrial Fibrillation, Valvular Heart Disease

Intervention / Treatment
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* Drug: continue warfarin through the procedure
* Drug: Hold warfarin
* Drug: Warfarin held with heparin transition.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: scheduled for clinically indicated permanent pacemaker or implantable cardioverter-defibrillator currently on chronic warfarin therapy Exclusion Criteria: unwilling to participate in trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Moderate risk patients (afib, mechanical aortic valve) randomized to continue coumadin at their usual dose through the procedure. | Drug: continue warfarin through the procedure<br>* The usual dose of warfarin (resulting in a therapeutic INR) is taken throughout the peri-procedural period.<br>|
| Active Comparator: 2<br>Moderate risk patients randomized to hold their coumadin for 4-5 days prior to the procedure (to allow the INR to normalize). | Drug: Hold warfarin<br>* For moderate risk patients, warfarin will be held for 4-5 days prior to the procedure.<br>|
| Experimental: 3<br>High risk patients (mechanical mitral valve, prior stroke, current deep vein thrombosis, hypercoagulable syndrome) randomized to continue coumadin at the usual dose through the procedure. | Drug: continue warfarin through the procedure<br>* The usual dose of warfarin (resulting in a therapeutic INR) is taken throughout the peri-procedural period.<br>|
| Active Comparator: 4<br>High risk patients randomized to holding coumadin for 4-5 days and using bridging anticoagulation with heparin while the coumadin is held. | Drug: Warfarin held with heparin transition.<br>* For high risk patients, warfarin is held for 4-5 days prior to the procedure and heparin is given to provide anticoagulation while the INR is subtherapeutic.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding Complication | Significant bleeding was defined as extracardiac bleeding or pocket hematomas that required additional intervention and/or temporary discontinuation of anticoagulation therapy. | 30 days | 
| Thromboembolic Events |  | 30 days | 
| Anticoagulant Related Complications | Defined as warfarin induced skin necrosis or heparin-induced thrombocytopenia | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bleeding, anticoagulation, pacemaker, implantable cardioverter-defibrillator, patients undergoing implantation of a pacemaker or defibrillator (ICD)