BRUISE CONTROL: Continued Warfarin Beats Heparin Bridging in ICD/Pacemaker Implants

Shelley Wood and Steve Stiles

May 12, 2013

DENVER, CO — Patients at high risk of thromboembolism who require pacemaker or implantable cardioverter-defibrillator (ICD) surgery can safely remain onwarfarin, without interruption, rather than be bridged with heparin, results of the BRUISE CONTROL study suggest[1].

Dr David H Birnie (Ottawa Heart Institute, ON) and colleagues report their findings online May 9, 2013 in the New England Journal of Medicine, timedto coincide with Birnie's presentation of the study at the Heart Rhythm Society (HRS) 2013 Scientific Sessions .

Guidelines currently recommend that patients at high risk for thromboembolic events be bridged with heparin therapy, with their warfarin stopped five days before their procedure, the group notes. But few randomized, controlled studies have actually given the strategy a proper test, especially compared with simply maintaining patients on warfarin throughout their procedures.

In BRUISE CONTROL's >600 patients who at baseline had a predicted annual stroke risk of >5%, the continued-warfarin approach was associated with a "highly significant reduction in the rate of device-pocket hematoma compared with heparin bridging," Birnie noted when formally presenting the trial at the HRS sessions. The risk of that primary end point was reduced by 81% (p<0.001).

Dr David H Birnie

"We also found that operating with continued warfarin, with a median [international normalized ratio] INR of 2.3, was not associated with any major perioperative bleeding events," he said.

At a press conference on the trial, Birnie observed that all the components of the primary end point, which reflected different kinds of pocket hematoma, were significantly reduced in the continued-warfarin group. "So the study was unequivocally positive."

Reporters asked Birnie whether the trial's findings in patients who took warfarin or, if bridged, low-molecular-weight heparin or unfractionated heparin, could be extrapolated to surgery-scheduled patients who are on dabigatran (Pradaxa, Boehringer Ingelheim), rivaroxaban (Xarelto, Bayer/Johnson & Johnson), or apixaban (Eliquis, Bristol-Myers Squibb/Pfizer).

"This does not in any way apply to the new agents," he said. "The whole risk/benefit ratio with the new agents is completely different from [that of] warfarin. Their onset of action is in hours as opposed to five days."

The trial had randomized 338 patients to heparin bridging and 343 to warfarin continuation by the time the data safety monitoring board recommended early termination. A second prespecified interim analysis suggested a significant advantage for warfarin continuation. The rate of clinically relevant pocket hematoma was 16% in the heparin-bridging group and only 3.5% in the continued-warfarin group (p<0.001).

Relative Risk (RR) for Outcomes, Continued Warfarin (N=343) vs Heparin Bridging (n=338)

End point RR (95% CI) p
Primary end point    
Clinically significant hematoma 0.19 (0.10–0.36) <0.001
Primary-end-point components    
Hematoma prolonging hospitalization 0.24 (0.08–0.72) 0.006
Hematoma requiring >24-h anticoagulation interruption 0.20 (0.10–0.39) <0.001
Hematoma requiring reoperation 0.21 (0.05–1.00) 0.03

Major surgical and thrombotic complications were few, with no significant differences between treatment groups.

Moreover, Birnie observed in his presentation, "patients in the continued- warfarin arm had much greater satisfaction with their perioperative anticoagulation management." That was reflected in their higher scores on the seven-point Likert scale, which averaged 6.4 in contrast to 5.9 for patients in the heparin-bridging group (p<0.001).

Dr John D Day

After Birnie's presentation, session comoderator Dr John D Day (Intermountain Medical Center, Salt Lake City, UT) asked him whether the trial has influenced practice at his center. He also asked what other influences on outcomes were observed.

"For sure, our clinical practice changed as soon as we saw these results," Birnie replied. And "there were only three independent predictors of pocket-hematoma formation in multivariate analysis. Number one, and far and away the most important, was to do it on continued warfarin. Number two, aspirin doubled the risk of pocket hematoma. Number three, a result that was a surprise to us: the presence of diabetes seemed to be protective against pocket hematoma."

Birnie's institution has received grants from the Canadian Institute of Health Research; he has received grants from Sanofi. Disclosures for the coauthors are available at nejm.org.

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