Authors
Pitt B, Pfeffer MA, Assmann SF, et al. for the TOPCAT Investigators
Title
Pacemaker or Defibrillator Surgery without Interruption of Anticoagulation
References
N Engl J Med 2013.368(22):2084-93
Background
Many patients requiring pacemaker or implantablecardioverter-defibrillator (ICD) surgery are taking warfarin. For patients at high risk for thromboembolic events, guidelines recommend bridging therapy with heparin; however, case series suggest that it may be safe to perform surgery without interrupting warfarin treatment. There have been few results from clinical trials to support the safety and efficacy of this approach.
Purpose
Patients were randomly assigned with an annual risk of thromboembolic events of 5% or more to continued warfarin treatment or to bridging therapy with heparin.
Design
Multicentre unblinded randomized controlled trial with 17 centres in Canada and 1 centre in Brazil. Inclusion criteria Annual predicted risk of thromboembolism of 5% or more Taking warfarin Required nonemergency device (pacemaker or ICD) surgery including implantationof a new device, pulse-generator change, lead replacement, or pocket revision. The primary outcome was clinically significant device-pocket hematoma, which was defined as device-pocket hematoma that necessitated prolonged hospitalization, interruption of anticoagulation therapy, or further surgery (e.g., hematoma evacuation) Secondary outcomes included each component of the primary outcome, the composite of all othermajor perioperative bleeding events (hemothorax, cardiac tamponade, or clinically significant pericardial effusion), thromboembolic events (transient ischemic attack, stroke, deep-vein thrombosis,pulmonary embolism, systemic embolism, or valve thrombosis), death from any cause, quality of life, perioperative pain, and patient satisfaction.
Exclusion Criteria
Patients not fulfilling the inclusion criteria.
Follow-Up
All patients were followed up at 1-2 weeks post procedure and during nay hospital visits or admissions.
Treatment Regimen
In the continued-warfarin group, INR on the day of surgery was targeted to be 3.0 or lower, except for patients with one or more mechanical valves, for whom an INR of 3.5 or less was permitted. Patients in the heparin-bridging group discontinued warfarin 5 days before the procedure and started receiving full therapeutic doses of low molecular weight heparin or intravenous heparin 3 days before the procedure. For patients receiving bridging therapy with low-molecular-weight heparin, the final dose was given the morning of the day before the procedure (i.e., >24 hours before the procedure). For patients receiving bridging therapy with intravenous heparin, the infusion was discontinued at least 4 hours before surgery. The administration of heparin was reinitiated 24 hours after the procedure and was continued until a therapeutic INR was achieved.
Results
Primary Endpoints The data and safety monitoring board recommended termination of the trial after the second prespecified interim analysis. Clinically significant device-pocket hematoma occurred in 12 of 343 patients (3.5%) in the continued-warfarin group, as compared with 54 of 338 (16.0%) in the heparin-bridging group (relative risk, 0.19; 95% confidence interval, 0.10 to 0.36; P<0.001). Secondary Outcomes Major surgical and thromboembolic complications were rare and did not differ significantly between the study groups. They included one episode of cardiac tamponade and one myocardial infarctionin the heparin-bridging group and one stroke and one transient ischemic attack in the continued-warfarin group.
Summary
As compared with bridging therapy with heparin, a strategy of continued warfarin treatment at the time of pacemaker or ICD surgery markedly reduced the incidence of clinically significant device-pocket hematoma.