A strategy of forgoing bridging anticoagulation was noninferior to and had a lower risk of major bleeding than perioperative bridging anticoagulation in patients with atrial fibrillation (AF) who stopped taking warfarin prior to surgery, according to study findings in the New England Journal of Medicine.
Multiple observational studies have assessed the potential timing and dosing of perioperatve bridging—administered as a low-molecular-weight herapin—but a lack of evidence has resulted in inconsistent practice guidelines and recommendations.
James D. Douketis, MD, and colleagues designed the BRIDGE trial (Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery), to answer the question: Is heparin bridging needed during the interruption of warfarin therapy before and after an operation or other invasive surgical procedure?
The randomized, double-blind, placebo-controlled trial enrolled 1884 patients between July 2009 and December 2014 – 950 of whom received no bridging therapy and 934 of whom received bridging therapy. By the conclusion of the study, 71 patients had discontinued participation. The mean patient age was 71.7 years, and 73.4% of the patients were male. Eligible patients were 18 years or older, had chronic atrial fibrillation or flutter, had received warfarin therapy for 3 months or longer, were undergoing an elective operation or other elective invasive procedure, and had at least one CHADS2 stroke risk factor (congestive heart failure or left ventricular dysfunction, hypertension, aged 75 years or older, diabetes mellitus or ischemic stroke, systemic embolism, or transient ischemic attack).
Participants were randomly assigned to either receive bridging anticoagulation therapy (dalteparin sodium, 100 IU per kg of body weight, administered subcutaneously twice daily) or to receive no bridging therapy (a matching subcutaneous placebo). Warfarin treatment stopped 5 days before the procedure, and administration of the study drug began 3 days before the procedure.
All study outcomes were assessed by 37 days after the procedure was performed. The most common procedures performed were gastrointestinal, cardiothoracic, and orthopedic. Overall, 89.4% of patients underwent a procedure that was classified as minor/low bleeding risk according to the study’s prespecified classification.
At 30 days post procedure, rates of arterial thromboembolism were comparable in the nobridging vs bridging groups (0.4% vs 0.3%), with a median time to event of 19 days post procedure.
Major bleeding occurred in 1.3% of patients in the no-bridging group and in 3.2% of patients in the bridging group, indicating that no bridging is superior to bridging with regard to major bleeding.
Furthermore, forgoing bridging was associated with a risk of minor bleeding significantly lower than the risk associated with bridging (12.0% vs. 20.9%, P<.001). Patients did not experience a significant difference in the rates of acute myocardial infarction, deep vein thrombosis, pulmonary embolism, or death in either group.
“We found that in patients with atrial fibrillation […] a strategy of discontinuing warfarin treatment without the use of bridging anticoagulation was noninferior to the use of bridging anticoagulation for the prevention of arterial thromboembolism,” the researchers wrote. “In addition, bridging conferred a risk of major bleeding that was nearly triple the risk associated with no bridging.”
- Douketis JD, Spyropoulous AC, Kaatz S, Becker RC, et al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Eng J Med. 2015;373:823-833.
- Slomski A. Clinical Trials Update: Bridging Anticoagulation Offers No Perioperative Benefit. JAMA. 2015;315:762.