Bridging Anticoagulation in Patients Who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery (BRIDGE)

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Accession Number

Study Type
Clinical Trial

Collection Type
Open BioLINCC Study See bottom of this webpage for request information

Study Period
July 2009 - February 2015

NHLBI Division

Dataset(s) Last Updated
January 3, 2018


Commercial Use Data Restrictions No

Data Restrictions Based On Area Of Research No


To determine if bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure.


Approximately one in six warfarin–treated patients with atrial fibrillation will undergo an elective operation or other elective invasive procedure, which requires perioperative interruption of warfarin treatment in order to reduce the risk of major bleeding. Multiple observational studies have assessed the timing and dosing of perioperative bridging with low-molecular-weight heparin (LMWH); however, the fundamental question of whether bridging anticoagulation is necessary during perioperative warfarin interruption has remained unanswered. As a result, there was insufficient evidence for practice guidelines which created weak and inconsistent recommendations regarding the need for bridging anticoagulation.

The BRIDGE trial was designed to address a simple question: in patients with atrial fibrillation, is heparin bridging needed during interruption of warfarin therapy before and after an operation or other invasive procedure? The primary efficacy outcomes were arterial thromboembolism, including stroke (ischemic or hemorrhagic), transient ischemic attack, and systemic embolism, and the primary safety outcome was major bleeding. The secondary efficacy outcomes were acute myocardial infarction, deep-vein thrombosis, pulmonary embolism, and death, and the secondary safety outcome was minor bleeding.


There were 1884 patients assigned to either the placebo or LMHW (dalteparin) treatment arms of the BRIDGE study. Of these, 918 participants completed the placebo treatment arm and 895 participants completed the dalteparin treatment arm.

Patients were eligible to participate in the trial if they were 18 years of age or older; had chronic (permanent or paroxysmal) atrial fibrillation or flutter, confirmed by means of previous electrocardiography or pacemaker interrogation; had received warfarin therapy for 3 months or longer, with an international normalized ratio (INR) therapeutic range of 2.0 to 3.0; were undergoing an elective operation or other elective invasive procedure that required interruption of warfarin therapy; and had at least one of the following CHADS2 stroke risk factors: congestive heart failure or left ventricular dysfunction, hypertension, age of 75 years or older, diabetes mellitus, or previous ischemic stroke, systemic embolism, or transient ischemic attack.

Patients were not eligible if they had a surgery, diagnostic lab value or recent event that would be considered a safety issue or disqualifying event.


Patients were randomly assigned to receive bridging anticoagulation therapy with dalteparin sodium (100 IU/kg) or no bridging therapy with a placebo. Randomization was stratified according to study center. Study drugs were provided in identical vials and administered subcutaneously twice daily.

The administration of study drug followed a standardized perioperative management protocol. Warfarin treatment was stopped 5 days before the procedure, and administration of the study drug (dalteparin or matching placebo) was started 3 days before the procedure until the morning, approximately 24 hours, before the procedure. Warfarin treatment was restarted on the evening of or the day after the procedure, at the patient’s usual dose. Administration of dalteparin or placebo was resumed 12 to 24 hours after a minor (or low-bleeding-risk) procedure and 48 to 72 hours after a major (or high-bleeding-risk) procedure. The designation of low or high bleeding risk procedure was guided by means of a classification scheme, but the final determination of risk was left to the investigator’s discretion. The patient continued to take the study drug after the procedure until the INR was 2 or higher on one occasion.

Follow-up encounters were weekly telephone calls, with the final encounter 30 to 37 days after the procedure. All study outcomes were assessed by 37 days after the procedure.


The incidence of arterial thromboembolism was 0.4% in the placebo group and 0.3% and the dalteparin group. Major bleeding occurred in 1.3% of the placebo group and 3.2% of the dalteparin group. The risk of minor bleeding was significantly lower in the placebo group than in the dalteparin group. There were no significant differences between the groups in secondary efficacy outcomes. In conclusion, discontinuing warfarin treatment without the use of bridging anticoagulation was noninferior to the use of bridging anticoagulation.

Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. The New England journal of medicine. 2015; 373(9):823-833. doi:10.1056/NEJMoa1501035.

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