The need for an elective surgery or invasive procedure is common among patients receiving warfarin for atrial fibrillation. In approximately one quarter of such procedures, bridging anticoagulation during perioperative interruption of warfarin is prescribed with the goal of reducing arterial embolism.1 Mounting evidence from nonrandomized comparisons suggests that this strategy may not achieve its stated goal and may increase major bleeding compared with interruption of warfarin alone.1-3 However, until recently, high-quality randomized controlled trial data were lacking.
Enter the BRIDGE (Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery) trial. BRIDGE was a randomized, double-blind, placebo-controlled study of 1,884 adults on warfarin for chronic atrial fibrillation or atrial flutter who were scheduled for an elective procedure requiring interruption of oral anticoagulation. The study excluded subjects with a mechanical heart valve, recent embolic event, or major bleeding; renal dysfunction (creatinine clearance < 30 mL/min); or planned cardiac, intracranial, or intraspinal surgery. All subjects discontinued warfarin five days before surgery and resumed warfarin within a day afterward. Subjects were randomized in 1:1 fashion to receive subcutaneous dalteparin 100 IU/kg twice daily or matching placebo from three days to 24 hours before the procedure and for five to 10 days after the procedure. The study drug was resumed 12 to 24 hours after a minor procedure and 48 to 72 hours after a major procedure. The primary efficacy outcome was arterial thromboembolism (stroke, transient ischemic attack, or systemic embolism) at 30 days after the procedure. The principal safety outcome was major bleeding. All outcomes were confirmed by independent adjudicators who were blinded to treatment assignment.
Study subjects were predominantly elderly (mean age, 71.7 years) and male (73.4%). Mean CHADS2 score was 2.3. The most common procedures were gastrointestinal, cardiothoracic, and orthopedic. There was no difference in the incidence of arterial thromboembolism between the bridging group and the placebo group (0.3% vs. 0.4%; p=0.73). Major bleeding was significantly greater in the bridging group (3.2% vs. 1.3%; p=0.005), as was minor bleeding (20.9% vs. 12.0%; p<0.001). There were no fatal hemorrhages.
In Brief
Dr. Douketis and colleagues have shown that, in patients with atrial fibrillation who require perioperative interruption of warfarin for an elective procedure, use of bridging anticoagulation increases bleeding without reducing thromboembolism. A recently published retrospective cohort study in patients receiving warfarin for a history of venous thromboembolism yielded similar results.4 Collectively, these data suggest that the common practice of perioperative bridging in patients on warfarin is overutilized and that curtailing of this practice in appropriately selected patients will result in improved outcomes.
However, unlike the historic London Bridge memorialized in the famous nursery rhyme, perioperative bridging has not fallen down completely. There may be high-risk patients or surgeries for which bridging is appropriate. For example, patients with mechanical valves, an arterial embolic event within the previous 12 weeks, and those undergoing certain high-risk surgeries (e.g., carotid endarterectomy, major cancer surgery, cardiac surgery, neurosurgery) were not included in BRIDGE, and patients with very high CHADS2 scores (5 to 6) comprised only 3 percent of the study population. More data are needed to determine whether bridging is indicated in these settings. Some answers may emerge from the ongoing, randomized, double-blind PERIOP 2 trial (clinicaltrials.gov Identifier NCT00432796), which is similar to BRIDGE in design but includes some high-risk groups (e.g., patients with mechanical valves) that were excluded from participation in BRIDGE.
For more on this topic, see the Literature Scan article published in the July 2015 issue of ASH Clinical News.
References
Competing Interests
Dr. Cuker indicated no relevant conflicts of interest.
