By Harold L. Karpman, MD, FACC, FACP
Clinical Professor of Medicine, UCLA School of Medicine
Dr. Karpman reports no financial relationships relevant to this field of study.
SYNOPSIS: In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was not inferior to perioperative bridging with low molecular weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding.
SOURCE: Douketis JD, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med 2015;373:823-833.
For patients with atrial fibrillation who are receiving warfarin and require an elective operation or other elective invasive procedure, the need for bridging anticoagulation during perioperative interruption of warfarin therapy has long been uncertain.1-3 Bridging anticoagulation is usually achieved using low-molecular-weight-heparin to minimize or eliminate the time that patients do not have an adequate level of anticoagulation with the intent of minimizing the risk of perioperative arterial thromboembolism.4 Douketis et al conducted a trial known as the Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery (BRIDGE) to determine whether heparin bridging was required during interruption of warfarin therapy before or after an elective operation or other invasive procedure.5
BRIDGE was a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients with atrial fibrillation were randomly assigned to receive either bridging anticoagulation therapy with low-molecular-weight-heparin or matching placebo administered subcutaneously twice daily from 3 days before the procedure until 24 hours before the procedure and then for 5-10 days after the procedure. The Duke Clinical Research Institute managed this study, which was conducted at 108 sites in the United States and Canada. The trial enrolled 1884 patients who had received warfarin therapy for ≥ 3 months and were undergoing an elective operation or other elective invasive procedure that required interruption of warfarin therapy. The results revealed that forgoing bridging anticoagulation was not inferior to perioperative bridging with low molecular weight heparin for the prevention of arterial thromboembolism and for decreasing the risk of major bleeding.
COMMENTARY
This important study determined that discontinuing warfarin treatment without the use of bridging anticoagulation was not inferior to the use of bridging anticoagulation for the prevention of arterial thromboembolism. Also, the risk of major bleeding nearly tripled in the bridging group compared to the no bridging group. There was less minor bleeding without bridging, and there were no significant differences between groups with regard to myocardial infarction, venous thromboembolism, or death. Analyzing all the data revealed there is a net clinical benefit in favor of the strategy of forgoing bridging as compared with perioperative bridging with low-molecular-weight-heparin. The findings were consistent with a published meta-analysis of observational studies comprised of 12,278 patients, which also revealed no significant difference in the rate of arterial thromboembolism but a higher rate of major bleeding associated with bridging.6
There are major potential limitations in this very complex trial. First, the mean CHADS2 score was 2.3, which is similar to the score among patients with atrial fibrillation who were assessed in the most recent trials in patient registries that included only a few higher-risk patients with high CHADS2 scores of 5 or 6. Also, patients undergoing major surgical procedures often associated with high rates of arterial thromboembolism and/or bleeding, such as carotid endarterectomy, major cardiac surgery, cardiac surgery, or neurosurgery, were not represented in the trial since the procedures performed were more representative of the most common interventions patients undergo during an interruption of therapeutic anticoagulation, the majority of which are low-risk procedures such as colonoscopy or surgical procedures performed in an ambulatory environment. Finally, the results of this trial may have diminished relevance because of the decreasing use of warfarin in the treatment of patients with atrial fibrillation giving the availability and the increasing use of the newer oral anticoagulant drugs, which are now so widely used.4
It certainly appears patients receiving warfarin therapy for atrial fibrillation can safely forgo bridging with heparin therapy if they are undergoing low-risk procedures such as colonoscopy or simple surgery performed in an ambulatory environment. However, since patients undergoing major surgical procedures associated with high rates of arterial thromboembolism and bleeding, such as carotid endarterectomy, major cancer surgery, cardiac surgery, or neurosurgery, were not represented in this trial, one cannot conclude that anticoagulant bridging is unnecessary when these procedures are scheduled to be performed.
REFERENCES
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Kearon C, et al. Management of anticoagulation before and after elective surgery. N Engl J Med1997;336:1506-1511.
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Piazza G, et al. Periprocedural management of the chronically anticoagulated patient: Critical pathways for bridging therapy. Crit Pathw Cardiel 2003;2:96-103.
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Gallego P, et al. Bridging evidence-based practice and practice-based evidence in peri-procedural anticoagulation. Circulation 2012;126:1573-1576.
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Baron TH, et al. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med 2013;368:2113-2124.
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Douketis JD, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med 2015;373:823-833.
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Siegel D, et al. Periprocedural heparin bridging in patients receiving vitamin K antagonist: Systematic review and meta-analysis of bleeding and thromboembolic rates. Circulation 2012;126:1630-1639.
