Implantable Devices and Heparin Bridging

Bradley P. Knight, MD, FACC, FHRS, Editor-in-Chief
Bradley P. Knight, MD, FACC, FHRS, Editor-in-Chief

An 80-year-old man with permanent atrial fibrillation (AF) and complete heart block needs his pacemaker generator changed for battery depletion. He has a history of hypertension and prior stroke. His CHADS2 score is 4. He has been taking warfarin for several months and his INR is 2.3. How would you manage his anticoagulation around the time of his pacemaker generator change?

For many years, patients taking warfarin who were scheduled for surgery have been “bridged” with heparin. The idea was to optimize perioperative hemostasis. The availability of low-molecular-weight heparin, which can be given as an outpatient, made this bridging approach more attractive. However, heparin is inconvenient, expensive, and can cause postoperative bleeding itself. For unclear reasons, perhaps because the dose of heparin given during heparin bridging is far more than needed, or because of the other properties of heparin including its thrombolytic and anti-inflammatory effects, postoperative bleeding appears to be more common with heparin than with warfarin. Because of this, some physicians have started to perform various procedures and minor surgeries on uninterrupted warfarin. This has actually become standard practice at many centers for catheter ablation procedures. However, it has not been convincingly shown that performing device procedures is safer when done on uninterrupted warfarin compared with heparin bridging.

A recent study has addressed this very scenario: BRUISE CONTROL. The study was presented at the Heart Rhythm Society Scientific Sessions in Denver in May 2013, and was simultaneously published in the New England Journal of Medicine.1 The investigators randomly assigned patients who were scheduled to undergo device implantation and had an annual risk of thromboembolic events of ≥5%, to continued warfarin or to bridging with heparin. In the continued-warfarin group, the international normalized ratio (INR) on the day of surgery was targeted to be ≤3.0, except for patients with a mechanical valve, for whom an INR of ≤3.5 was allowed. Patients in the heparin-bridging group discontinued warfarin five days preoperatively and started receiving full therapeutic doses of low-molecular-weight heparin or intravenous heparin three days preoperatively. Clopidogrel was stopped for five days before surgery in patients who had undergone implantation of a bare-metal stent more than one year previously, and aspirin was continued. Interestingly, to minimize bias, a separate, blinded care team was made available to manage any postoperative hematomas.

The study was terminated early when it was recognized that there were far more complications in the heparin-bridging group. A clinically significant device-pocket hematoma, defined as a hematoma that necessitated prolonged hospitalization, interruption of anticoagulation, or hematoma evacuation, occurred in 3.5% in the continued-warfarin group, as compared with 16.0% in the heparin-bridging group (P<0.001). Major surgical and thromboembolic complications were rare and did not differ significantly between the study groups. They included one episode of cardiac tamponade in the heparin-bridging group.

Although this study provides support for the performance of cardiac device implantation in patients on uninterrupted warfarin, it is important to recognize that this study cannot be applied to all patients taking warfarin. For example, patients taking warfarin for AF-related stroke prevention were enrolled only if they had a measured risk of stroke that exceeded 5% per year. The mean CHADS2 score was 3.4 in the study, and about one-third of patients had a mechanical valve. Patients with a CHADS2 score of 2 have an annual stroke risk of about 4%. Therefore, this study does not apply to many patients taking anticoagulation for AF. Most patients on warfarin should probably have their warfarin stopped in advance of device implantation and receive no heparin bridging. The BRUISE CONTROL study also does not apply to patients taking one of the newer oral anticoagulants.

It is interesting that the authors state in the introduction that the current guidelines recommend interruption of oral anticoagulation therapy and the use of bridging therapy with heparin around the time of surgery, and reference the guidelines from the American College of Chest Physicians.2 There is actually not a consensus among the societal guidelines on this issue. The most recent ACC/AHA/ESC AF Guidelines that addressed this issue in 20063 state that “in patients with AF who do not have mechanical valves, however, based on extrapolation from the annual rate of thromboembolism in patients with nonvalvular AF, it is the consensus of the Writing Committee that anticoagulation may be interrupted for a period of up to 1 week for surgical or diagnostic procedures that carry a risk of bleeding without substituting heparin … unless they are high-risk patients (particularly those with prior stroke, TIA, or systemic embolism) or when a series of procedures requires interruption of oral anticoagulant therapy for longer periods.”3 The challenge now is to determine which patients are at a high enough risk to recommend that their procedure be done on uninterrupted warfarin rather than simply stopping it. 

The investigators of the BRUISE CONTROL study should be commended for performing this study. It is also noteworthy that they completed this study with no commercial support. They have shown that device surgery is safer and more preferred when done on uninterrupted warfarin rather than with heparin bridging. However, these data do not apply to lower risk patients on warfarin. Until proven otherwise, device surgery on patients taking warfarin to reduce their risk of AF-related stroke and have a CHADS2 score of 2 or less, should probably be done after stopping their warfarin and not using any heparin bridging. 

Sincerely,

Bradley P. Knight, MD, FACC, FHRS

Editor-in-Chief, EP Lab Digest®

DrBradKnightEPLD@gmail.com

References

  1. Birnie DH, Healey JS, Wells GA, et al. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med. 2013. May 9, 2013. DOI: 10.1056/NEJMoa1302946.
  2. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e326S-e350S. [Erratum, Chest. 2012;141:1129.]
  3. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol. 2006;48:854-906.