Study Expected to Impact Device Surgeries Worldwide

July 2013

A gloved hand holding a blue pill
Millions of people around the world use the drug warfarin to reduce the risk of stroke from blood clots. Standard practice has been for patients to stop taking warfarin when undergoing surgery to implant a device such as a pacemaker. New research from the University of Ottawa Heart Institute is expected to change this practice worldwide.

For decades, patients taking the anti-clotting drug warfarin who required the implantation of a pacemaker or implantable cardioverter defibrillator have posed a dilemma. If they are at moderate to high risk of stroke caused by a blood clot, how are doctors to balance the risk of surgical bleeding from anti-clotting drugs with the need to prevent potentially lethal clot formation?

Though preventing stroke is a major concern, “bleeding around device procedures is also a serious issue for patients,” said David Birnie, MD, Director of the Arrhythmia Service at the University of Ottawa Heart Institute. “Bleeding can cause infection and other complications, which is why we take such care to prevent it.”

Until recently, he explained, the solution has been to temporarily “bridge” these moderate to high-risk patients onto another anti-clotting drug, heparin, during the time immediately before and after surgery (the perioperative period). Unlike warfarin, which remains in the bloodstream, the effects of heparin dissipate within a couple of hours once the drug is stopped. “So we’re actually doing the surgery with no blood thinner on board. We always thought that would be a better thing,” he said.

However, results from a major randomized trial led by Dr. Birnie and published May 9 in the New England Journal of Medicine turn this conventional wisdom on its head. In that trial, called BRUISE CONTROL (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial), patients at moderate to high risk of a thromboembolic event (stroke) randomly assigned to continue taking warfarin during the perioperative period had significantly less bleeding into the area surrounding the implanted device than patients bridged onto heparin.

“The feedback I’ve received from lots of physicians is that this is going to change guidelines.”

 

– Dr. David Birnie, Director, Arrhythmia Service, UOHI

 

In recent years, more and more doctors had questioned whether letting higher-risk patients continue to take warfarin immediately before and after device surgery actually increased the risk of bleeding during surgery. To definitively answer this question, BRUISE CONTROL enrolled 681 patients at 17 centres in Canada and one in Brazil who were scheduled to undergo non-emergency device implantation. About half of the patients received random assignment to continue warfarin. The other half was bridged to heparin, the current standard of care. The study was coordinated by the Heart Institute’s Cardiovascular Research Methods Centre under the direction of George Wells, PhD, who co-led the groundbreaking RAFT trial of cardiac resynchronization therapy.

The results were so statistically strong that the trial was stopped early by its safety board, following a second planned interim analysis. Only about 3 per cent of patients continuing warfarin experienced problematic bleeding compared with 16 per cent of patients who were switched to heparin. Patients who experienced bleeding during the trial reported more pain and decreased quality of life.

Overall, patients continuing on warfarin were happier with their anticoagulant treatment in the periods before and after surgery and, as an additional benefit, continuing warfarin is less expensive than bridging. Dr. Birnie called the results “a triple win. It’s better for the patients, it’s easier to administer and it’s cheaper.”

Exactly why continuing warfarin turned out to be safer is unclear. The authors of the study proposed that it could be a matter of early detection: If warfarin is not discontinued, any bleeding that is likely to happen occurs immediately, during surgery, where it can be observed instantly and managed quickly, before it causes complications.

They expect the BRUISE CONTROL results to immediately change clinical practice worldwide, potentially affecting hundreds of thousands of patients. As Dr. Birnie stated, “The feedback that I’ve received from lots of physicians is that this is going to change guidelines.” Already, he added, some other minimally invasive procedures, such as dental surgery and minor skin procedures, are done without stopping warfarin.

Bleeding in the area around a device such as this implantable cardioverter defibrillator can be a problem following the implant procedure. The BRUISE CONTROL study found that patients who stay on warfarin rather than switching to heparin for the procedure are significantly less likely to experience bleeding.

It is not known whether patients taking newer oral anti-clotting drugs, such as dabigatran, rivaroxaban and apixaban, can also safely continue their medications in the perioperative period. The Heart Institute team and its colleagues have recently opened a new clinical trial, BRUISE CONTROL 2, to examine this question in patients taking dabigatran.

The current BRUISE CONTROL results have wider implications for patients who may temporarily interrupt anticoagulation to undergo surgery or procedures. Guidelines suggest continuation of warfarin at the time of minor dental, dermatological or ophthalmological procedures. “Although not directly relevant,” explained Dr. Birnie, “data from our study are consistent with this recommendation, particularly since these other procedures are classified as low bleeding risk. This is in contrast to pacemaker or defibrillator implantation, which is considered to have increased bleeding risk.”

There are some surgeries, such as major abdominal, cardiothoracic or neurological, that are just too high risk to expect that continuing warfarin will ever be an option, the authors explain in the New England Journal paper. But some physicians have looked at performing other procedures and operations, such as coronary angiography and stenting, minor head and neck surgery, and colonoscopic polyp removal, on continued warfarin, and have seen low bleeding complications thus far. “Additional randomized controlled trials are needed, and none are currently under way. Hopefully, the results of our study will stimulate much needed high-quality research in these areas,” said Dr. Birnie.

“Overall, I think we’re going to see quite a drift away from bridging in lots of procedures,” he concluded. “But we need data in other areas. This is a question that cuts across many parts of medicine, not just device therapies.”

BRUISE CONTROL Support and Team

BRUISE CONTROL was supported by an operating grant from the Canadian Institutes of Health Research (CIHR) and an Innovations grant from the University of Ottawa Heart Institute Academic Medical Organization Alternate Funding Program.

Dr. David Birnie led the Heart Institute team, and the overall study coordinator was Karen MacDonald.

Other Ottawa-based BRUISE CONTROL team members include: