We found that in patients with atrial fibrillation who require perioperative interruption of warfarin treatment for an elective procedure, a strategy of discontinuing warfarin treatment without the use of bridging anticoagulation was noninferior to the use of bridging anticoagulation for the prevention of arterial thromboembolism; in addition, bridging conferred a risk of major bleeding that was nearly triple the risk associated with no bridging. There was also less minor bleeding without bridging than there was with bridging, and there was no significant difference between the groups with regard to myocardial infarction, venous thromboembolism, or death. Taken together, these findings show that there is a net clinical benefit in favor of a strategy of forgoing bridging, as compared with perioperative bridging with low-molecular-weight heparin.

The findings in our trial are consistent with those from nonrandomized comparisons of these strategies. A meta-analysis of observational studies involving a total of 12,278 patients with atrial fibrillation or mechanical heart valves who received or did not receive bridging with low-molecular-weight heparin showed no significant difference in the rate of arterial thromboembolism (odds ratio with bridging, 0.80; 95% CI, 0.42 to 1.54) but a higher rate of major bleeding (odds ratio, 3.60; 95% CI, 1.52 to 8.50) in association with bridging. In a substudy of the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY), in which patients with atrial fibrillation were randomly assigned to receive warfarin or dabigatran in an open-label manner, bridging anticoagulation was associated with a rate of major bleeding that was higher than that associated with no bridging (6.8% vs. 1.6%, P<0.001) among 1424 warfarin-treated patients who had treatment interruption for an elective procedure, and there was no significant effect on arterial thromboembolism (0.5% vs. 0.2%, P=0.32).

Background:
It is uncertain whether 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. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding.

Methods:
We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding.

Results:
In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], −0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority).

Conclusions:
In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; BRIDGE ClinicalTrials.gov number, NCT00786474.)

Trial,Population,Interventions,Results
COMPARE,"Catheter ablation of AF N = 1,584",Uninterrupted warfarin vs interrupted warfarin with low-molecular weight bridging,"Significant reduction in stroke (0.25% vs 3.7%), TIA (0% vs 1.3%), and minor bleeding with uninterrupted warfarin"
VENTURE-AF,Catheter ablation of AF N = 248,Uninterrupted rivaroxaban vs uninterrupted VKA,No difference in overall low incidence of major bleeding (0.4%) or thromboembolic events (0.8%)
RE-CIRCUIT,Catheter ablation of AF N = 704,Uninterrupted dabigatran vs uninterrupted warfarin,Significant reduction in major bleeding events with dabigatran (1.6% vs 6.9%)
BRUISE-CONTROL,Pacemaker or defibrillator implantation N = 343,Uninterrupted warfarin vs interrupted warfarin with heparin bridging,Significant reduction in pocket hematoma (3.5% vs 16%)

Background: The safety of anticoagulation interruption in patients requiring surgical or invasive procedures remains unclear. We thus performed a systematic review and meta-analyses of randomized controlled trials (RCTs) and non-randomized studies (NRS).

Methods: MEDLINE, Embase and Central databases were searched to March 2017 without date or language restrictions. We considered RCTs and NRS comparing anticoagulation interruption with any anticoagulation (continuation or heparin bridging) in adult surgical patients taking oral anticoagulation. Data were independently extracted. The quality of the evidence was assessed following recommendations from the Cochrane collaboration (GRADE approach). Risk ratios were calculated for 30-day events: thromboembolic (TE) events, major bleeding and mortality. Additional analyses explored the effects of different anticoagulation strategies.

Results: Twelve reports were included: 4 RCTs (2190 participants) and 8 NRS (18993 participants). Trials included mostly participants with atrial fibrillation. Interrupting anticoagulation did not seem to increase TE events (RR 0.65, 95% CI [0.33, 1.30]-4 studies, 2190 participants) and resulted in less bleeding (RR 0.41, 95% CI [0.22, 0.78]-3 studies, 2126 participants) compared to anticoagulation continuation or heparin bridging. The GRADE assessment was moderate. Similar results were found in non-randomized studies, but the quality of the evidence was low. Possible strategy-specific effects were identified: forgoing heparin bridging seemed beneficial, but these effects were less clear with other strategies.

Conclusion: Interrupting anticoagulation in patients requiring invasive procedures did not seem to result in harm and protected against major bleeding. Uncertainty remains regarding the safety of this strategy in indications other than atrial fibrillation and in moderate- to high-risk surgery.

Study Registration: http://www.en.anaesthesie.usz.ch/research/Pages/Study-protocols.aspx.

A meta-analysis of > 19,000 patients who underwent a procedure in the randomized trials comparing DOACs vs warfarin in atrial fibrillation was reported as well. Taken together, these studies reported rates of perioperative ATE of 0.5% to 1.0% and rates of major bleeding of 2% to 5%, which are comparable to rates observed in patients who receive non-standardized VKA interruption and resumption.
Additional evidence relating to pre-operative DOAC management involves patients undergoing catheter ablation for atrial fibrillation. An observational study reported an increase in bleeding with periprocedural DOAC continuation while another reported no difference in bleeding outcomes. A 306-patient randomized trial that compared 1-day DOAC interruption vs no interruption found no significant difference in bleeding outcomes (11.3% vs 9.7%; risk difference = 1.7%; 95% CI –5.5 to 8.8). An observational study assessing pacemaker/ICD implantation and minimal DOAC interruption (ie, skipping or delaying the immediate pre-procedure dose) reported a low rate (1.6%) of major pocket hematomas. A 25-patient observational study assessing DOAC continuation in patients having cataract surgery identified no bleeding events. An observational study comparing perioperative DOAC interruption and continuation in patients undergoing low-bleed-risk procedures reported lower rates of overall bleeding (OR = 0.59; 95%

Ci: 0.39 to 0.91) and minor bleeding (OR = 0.59; 95%

Ci: 0.37 to 0.93) with DOAC interruption, a finding that persisted after adjustment for confounders (OR = 0.62; 95%

Ci: 0.41 to 0.95).