Anticoagulation BRIDGEgate

SEPTEMBER 15, 2015
Bridging involves a parenteral anticoagulant, such as a low-molecular-weight heparin, used to rapidly achieve anticoagulation in the time it takes warfarin to produce a target therapeutic international normalized ratio (INR).

When a patient receiving warfarin undergoes elective surgery, a similar bridging process is often started. 
 
In this setting, the therapeutic goal is an adequate level of anticoagulation and minimized risk of arterial thrombosis. However, the benefits of lowering the risk of thrombosis may be outweighed by the risk of hemorrhage.
 
The BRIDGE trial proposed that foregoing this practice entirely would be non-inferior to bridge therapy with dalteparin in patients taking warfarin for atrial fibrillation.

This was a randomized, double-blind, placebo-controlled trial of adult patients with chronic atrial fibrillation who were undergoing an elective surgical procedure and had been on warfarin for at least 3 months or longer, targeting an INR therapeutic range of 2–3.
 
Patients also had to have had a least 1 of the following: congestive heart failure or left ventricular dysfunction, hypertension, age 75 or older, diabetes mellitus, previous ischemic stroke or transient ischemic attack (TIA), or systemic embolism. 
 
However, patients were excluded if they had an ischemic stroke, TIA, or systemic embolism within the 12 weeks before study enrollment, major bleeding within 6 weeks, creatinine clearance of <30 mL/min, platelets <100,000 per mm3, or planned cardiac, intracranial, or intraspinal surgery.

Five days prior to their surgical procedures, all patients stopped warfarin treatment and were randomly assigned to receive dalteparin or matched placebo between 3 days and 24 hours prior to the procedure, and then 5 to 10 days after the procedure.
 
The primary efficacy outcome was the incidence of arterial thromboembolism 37 days after the procedure, while the primary safety outcome was major bleeding.

A total of 1884 patients were randomized (placebo, 950; dalteparin 934). Four patients in the placebo arm (0.4%) and three in the dalteparin arm (0.3%) had an arterial thromboembolism during the study period, reaching the non-inferiority margin, but not superiority. 
 
However, significantly more patients who were bridged with dalteparin experienced both major bleeding events (placebo, n=12 (1.3%) vs dalteparin, n=29 (3.2%), p=0.005) and minor bleeding events (placebo, n=110 (12.0%) vs dalteparin, n=187 (20.9%), p<0.001). 
 
There was no difference in the incidence of death, myocardial infarction, deep vein thrombosis, or pulmonary embolism.

The authors concluded that forgoing bridge therapy in the population studied is non-inferior to bridging and may even lead to fewer bleeding complications. Without an increase in arterial thrombosis, this benefit may lead to fewer postoperative complications that contribute to prolonged lengths of stay, ultimately lowering the costs of health care.
 
Recommendations in the next-edition CHEST guidelines may shed more light on the impact of this study on standard practice.

Reference:
Douketis JD, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373(9):823-33.

Craig Cocchio, PharmD
Craig Cocchio, PharmD
Craig Cocchio, PharmD, BCPS, is an Emergency Medicine Clinical Pharmacist at Trinity Mother Frances Hospital in Tyler, Texas. Follow on Twitter @iEMPharmD and on his blog at empharmd.blogspot.com
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