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

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Bradycardia; Tachycardia; Valvular Heart Disease
• Intervention / Treatment: Drug: continue warfarin through the procedure; Drug: Hold warfarin; Drug: Warfarin held with heparin transition.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center
    • Columbia, Maryland, United States, 21045
      • Howard County General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• scheduled for clinically indicated permanent pacemaker or implantable cardioverter-defibrillator
• currently on chronic warfarin therapy

Exclusion Criteria:

• unwilling to participate in trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Moderate risk patients (afib, mechanical aortic valve) randomized to continue coumadin at their usual dose through the procedure.	Drug: continue warfarin through the procedure; The usual dose of warfarin (resulting in a therapeutic INR) is taken throughout the peri-procedural period.
Active Comparator: 2; 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; For moderate risk patients, warfarin will be held for 4-5 days prior to the procedure.
Experimental: 3; 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; The usual dose of warfarin (resulting in a therapeutic INR) is taken throughout the peri-procedural period.
Active Comparator: 4; 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.; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Alan Cheng, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: July 21, 2008
• First Submitted That Met QC Criteria: July 21, 2008
• First Posted (Estimate): July 23, 2008

Study Record Updates

• Last Update Posted (Actual): August 31, 2017
• Last Update Submitted That Met QC Criteria: July 31, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: bleeding; anticoagulation; pacemaker; implantable cardioverter-defibrillator; patients undergoing implantation of a pacemaker or defibrillator (ICD)"
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Diseases; Atrial Fibrillation; Bradycardia; Tachycardia; Heart Valve Diseases; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Warfarin
• Other Study ID Numbers: NA_00011273