麻豆传媒

DENVER -- Continuation of warfarin (Coumadin) through pacemaker or cardioverter-defibrillator procedures may be better for moderate-to-high risk patients than bridging with heparin, the randomized BRUISE CONTROL trial affirmed.

Clinically-significant hematomas in the device pocket were 81% less common without interruption of anticoagulation (P<0.001), David H. Birnie, MD, of the University of Ottawa Heart Institute in Ottawa, Ontario, and colleagues found.

While more serious risks were rare, no difference in major surgical or thromboembolic events emerged between groups, the researchers reported here at the Heart Rhythm Society meeting and simultaneously online in the New England Journal of Medicine.

The findings counter those of current guidelines, which recommend heparin bridging for device surgery, but confirm those of numerous case series from centers willing to overlook the guidelines given the lack of quality data to support them.

"It is reassuring that we now have a well done prospective randomized trial to support this practice," commented David E. Haines, MD, director of the Heart Rhythm Center at William Beaumont Hospital in Royal Oak, Mich.

Uninterrupted warfarin has been his strategy for the past 15 years.

For others, like Kevin Campbell, MD, an electrophysiologist at Wake Heart and Vascular in Raleigh, N.C., the findings are "a real game changer."

"This will change my practice," he said in an interview.

Not only was the strategy better for patients, but "it may very well reduce costs in the long run" by eliminating the need for the 2 or 3 days of typically in-hospital heparin dosing before and after the procedure, Campbell noted.

The findings should pave the way for a change in guidelines, Haines told 麻豆传媒.

While the trial was called BRUISE CONTROL (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial), these hematomas aren't any minor event, the researchers noted.

"Device-pocket hematomas can have serious consequences for patients, such as the need for prolonged cessation of all oral anticoagulation therapy with the attendant risk of thromboembolism, prolongation of hospitalization, the need for further surgery (e.g., hematoma evacuation), and an increased risk of infection," they wrote.

The trial included 681 patients on warfarin for moderate-to-high thromboembolic risk (5% or higher annual predicted risk) who were getting a new ICD or pacemaker or a related surgery for revision of the pocket, a new pulse-generator, or lead replacement.

They were randomized to stay on warfarin with an international normalized ratio (INR) targeted to 3.0 or lower on the day of surgery (3.5 or less for those with mechanical valves) or to stop warfarin 5 days before the surgery and start full therapeutic doses of low-molecular weight heparin or IV heparin 3 days before the procedure.

The study was single-blind, with patients aware of their treatment but the care team divided into two groups to maintain blinding.

One team knew the treatment assignment and dealt with the device. The other didn't know randomization and monitored the surgical wound throughout care and diagnosed and made all decisions about device-pocket hematomas.

For the primary outcome, clinically-significant hematomas occurred in 3.5% of the uninterrupted warfarin group versus 16% of the heparin bridged group, for a relative risk of 0.19 (95% confidence interval 0.10 to 0.36).

This endpoint included hematomas that necessitated prolonged hospitalization, interruption of anticoagulation therapy, or further surgery, such as to evacuate the pocket.

While there were no embolic events in the bridged group, one stroke and one transient ischemic attack occurred in the continued warfarin group. Both were in patients with nonvalvular atrial fibrillation, high stroke risk scores at baseline, and unintentionally subtherapeutic INRs at the time of surgery.

One cardiac tamponade case requiring pericardiocentesis occurred in the heparin-bridging group. No major perioperative bleeding events were recorded in either group.

Device-related infections occurred in six patients in the heparin bridging group versus two in the uninterrupted warfarin group (1.8% versus 0.6%, P=0.17).

All four deaths in the trial were among patients who stayed on warfarin: one from a cardiac cause before the surgery, one after the device procedure was cancelled due to metastatic pancreatic cancer diagnosis, one from intraperitoneal hemorrhage after paracentesis, and one from end-stage heart failure 10 days after surgery.

The researchers cautioned that their findings may not generalize to the newer anticoagulants or to lower thromboembolic-risk patients, who may not need any anticoagulation or bridging around their surgery, and shouldn't be applied to higher risk surgeries.

They also acknowledged the subjectivity of their primary endpoint and the possibility of unblinding, although they suggested this wasn't likely in many cases.

A better explanation for the seemingly counterintuitive results is that warfarin acts as a "stress test" for bleeding such that any excessive bleeding would be detected and managed while the wound is still open; whereas it might go undetected until the patient resumes full-strength anticoagulation after the procedure if they were bridged with heparin, the researchers suggested.

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