Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery | Clinical Trial - BRIDGE


The goal of the trial was to compare a strategy of anticoagulation interruption compared with low molecular weight heparin bridge therapy among patients with atrial fibrillation undergoing an invasive procedure.

Contribution to the Literature: The BRIDGE trial showed that low molecular weight heparin bridging did not prevent perioperative arterial thromboembolism, but did increase major bleeding.

Study Design

  • Randomized
  • Parallel
  • Placebo
  • Blinded

Patients with atrial fibrillation on warfarin therapy undergoing an invasive procedure had their anticoagulation therapy held. Patients were then randomized to placebo injection administered subcutaneous twice daily (n = 950) versus low molecular weight heparin; dalteparin 100 IU/kg subcutaneous twice daily (n = 934). Study medication was administered 3 days before and 5-10 days after the procedure.

  • Total number of enrollees: 1,884
  • Duration of follow-up: 30 days
  • Mean patient age: 72 years
  • Percentage female: 27%
  • Percentage diabetics: 41%

Inclusion criteria:

  • Patients at least 18 years of age
  • Permanent or paroxysmal atrial fibrillation/flutter
  • Patients with valvular-associated atrial fibrillation were eligible

Exclusion criteria:

  • Mechanical heart valve
  • Stroke, transient ischemic attack (TIA), or systemic embolism within previous 12 weeks
  • Major bleeding within previous 6 weeks
  • Creatinine clearance <30 cc/min
  • Thrombocytopenia (<100,000/m3)
  • Planned cardiac, intracranial, or intraspinal surgery

Other salient features/characteristics:

  • Mean CHADS2 score: 2.3
  • Prior stroke: 8.3%
  • Prior TIA: 8.3%
  • Mitral valve stenosis: 2.0%
  • 34% of patients were on aspirin therapy in which 59% continued this medicine perioperatively

Principal Findings:

The primary outcome, stroke, TIA, or systemic embolism, occurred in 0.4% of the no-bridge group versus 0.3% of the bridging group (p = 0.01 for noninferiority).

A secondary outcome was major bleeding: 1.3% vs. 3.2% (p = 0.005), respectively, for no-bridge versus bridge groups.


Among patients with atrial fibrillation on warfarin therapy, bridge therapy with low molecular weight heparin did not prevent perioperative arterial thromboembolic events; however, this strategy did increase major bleeding. This trial likely applies to most patients encountered in clinical practice.

Salient characteristics of enrollees include mean CHADS2 score of 2.3 and inclusion of patients with prior stroke/TIA, and valvular atrial fibrillation, including mitral stenosis. Patients with a markedly elevated CHADS2 score (5 or 6) were under-represented in this trial. Patients with a mechanical heart valve still require bridge therapy.


Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative Bridging Anticoagulation in Patients With Atrial Fibrillation. N Engl J Med 2015;Jun 22:[Epub ahead of print].

Keywords: Anticoagulants, Arrhythmias, Cardiac, Aspirin, Atrial Fibrillation, Dalteparin, Embolism, Heart Valves, Heparin, Low-Molecular-Weight, Ischemic Attack, Transient, Mitral Valve Stenosis, Primary Prevention, Stroke, Thrombocytopenia, Thromboembolism, Warfarin

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