Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation NEJM Aug 27, 2015

1. Perioperative Bridging Anticoagulation in Patients with Atrial FibrillationNEJM Aug 27, 2015

2. Abstract • Background: In patients with Afib, is Heparin bridging necessary during interruption of warfarin therapy for elective invasive procedures. • Methods: Eval for incidents of arterial thromboembolism (ATE) or major bleeding 30 days after procedure. • Results: Bridging group: ATE 0.3%, Major bleeding 3.2% Non bridging group: ATE 0.4%, Major bleeding 1.3%. • Conclusions: No bridging noninferior for prevention of ATE and superior for decrease of major bleeding risk.

3. BRIDGE trial • Warfarin typically stopped 5 days prior to elective procedures and restarted after procedure. Requires 5-10 days to attain therapeutic levels. • LMWH is typically used to minimize risk of ATE during interruption of Coumadin. • Multiple trials have addressed timing and dosing of LMWH bridging but none have evaluated whether bridging is actually necessary.

4. BRIDGE trial • Rationale for bridging has been that bleeding risk was acceptable because of the reduction in risk of ATE.

5. Methods • Design • Randomized double blind placebo controlled trial • Primary efficacy outcome was prevention of ATE • Primary safety outcome was reduction of major bleeding risk • Patients • Paroxysmal or permanent valvular/non-valvular Afib or Aflutter

6. On Coumadin at least 3 months with INR of 2.0-3.0 • At least one CHADS2 risk factors. • Exclusion criteria • Mechanical heart valve • CVA, TIA or systemic embolism within 12 weeks • Major bleeding within 6 weeks • CrCl < 30ml/min • Platelets < 100x10 per cubic mm

7. Cardiac, cranial, or intraspinal surgery. • Procedures • Warfarin stopped 5 days prior • Administration of either Dalteparin 100U/kg SC BID or placebo started 3 days before procedure, stopped 24 hours prior to procedure • Warfarin restarted evening or day after procedure

8. SC LMWH or placebo started 12-24 hours after low bleeding risk surgery, 48-72 hours after major bleeding risk surgery. • Continued until INR >2 on one occasion • Follow up telephone interviews weekly until 30-37 days after procedure • Management of antiplatelet therapy at investigator’s discretion. • Protocol adherence before procedure 86.5%, after procedure 96.5%

10. Statistical Analysis • Contemporaneous cohort studies suggested rate of ATE in bridging group would be 1% • Assumed rate of ATE would be 1% • 95% confidence interval calculated with use of methods based on Barnard’s test. • Sample of 1882 would give 90% power for 2 end points.

13. Results • 30 days after procedure • ATE • 0.4% in non bridging group • 0.3% in bridging group • P value: 0.01 for noninferiority, 95% CI -0.6-0.8 • Major bleeding • 1.3% in non bridging group • 3.2% in bridging group • P value: 0.005, 95% CI 0.2-0.78, RR 0.41

15. Discussion • Findings support that strategy of no bridging for patients with Afib who require interruption of Warfarin for an elective procedure is noninferior to bridging in the prevention of ATE and superior in reduction of major bleeding risk. • Support a net clinical benefit to foregoing perioperative bridging.

16. Discussion • Rational for bridging. • ATE may be more related to procedure type and intraoperative BP management. Minimal survival bias • Mean CHADS2 score was 2.3. Underrepresentation of higher CHADS2 scores. • Major surgical procedures were not included.

17. Discussion • Reduction in sample size during study. • Power was maintained for primary hypothesis • Did not consider prevalence of direct oral anticoagulants. • Higher proportion of previous TIA, CVA in bridging group.