Patients stopped taking warfarin 5 days before their procedure, and began subcutaneous dalteparin, 100 IU/kg, or an identical placebo 3 days before the procedure. The dalteparin/placebo was stopped 24 hours before the procedure and restarted after the procedure, until the patient’s INR was in the therapeutic range. Warfarin was resumed on the evening of the procedure or the following day.
The primary efficacy outcome was ATE, including stroke, TIA, or systemic embolism. The primary safety endpoint was major bleeding (defined as bleeding at a critical anatomic site, symptomatic or clinically overt bleeding, or a decrease in hemoglobin >2 g/dL). Secondary efficacy and safety outcomes included minor bleeding, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, and death. Outcomes were assessed within 37 days of the procedure.
The incidence of ATE was 0.4% (4 events) in the no-bridging group vs 0.3% (3 events) in the bridging group (95% CI, -0.6 to 0.8; P=.01 for non-inferiority; P=.73 for superiority). Major bleeding occurred in 1.3% of the no-bridging group (12 events) and in 3.2% of the bridging group (29 events), indicating that no bridging was superior in terms of the major bleeding outcome (number needed to harm [NNH]=53; relative risk [RR]=0.41; 95% CI, 0.20-0.78; P=.005). The no-bridging group also had significantly fewer minor bleeds in comparison to the bridging group (NNH=11; 12% vs 20.9%; P<.001). There were no differences between groups in other secondary outcomes.
WHAT'S NEW: High-quality evidence suggests it’s OK to stop warfarin before surgery
This is the largest good-quality study to evaluate perioperative bridging in patients with atrial fibrillation who were at low or moderate risk for ATE (CHADS2 score 0-4). Previous studies suggested bridging increased bleeding and offered limited benefit for reducing the risk of ATE. However, this is the first study to include a large group of moderate-risk patients (CHADS2 score 3-4). This trial provides high-quality evidence to support the practice of simply stopping warfarin in the perioperative period, rather than bridging with LMWH.
CAVEATS: Findings might not apply to patients at highest risk
Most patients in this study had a CHADS2 score ≤3. About 3% had a CHADS2 score ≥5 or higher. It’s not clear whether these findings apply to patients with a CHADS2 score of 5 or 6.
This trial categorized ATE risk using the CHADS2 score, rather than the CHA2DS2-VASc, which includes additional risk factors and may more accurately predict stroke risk. Both patients who received bridging therapy and those who did not had a lower rate of stroke than predicted by CHADs2. This may reflect a limit of the predictive value of CHADS2, but should not have affected the rate of bleeding or ATE outcomes in this study.
CHALLENGES TO IMPLEMENTATION: Physicians may hesitate to disregard current guidelines
Strokes are devastating events for patients, families, and physicians, and they pose a greater risk of morbidity and mortality compared to bleeding. However, this study suggests patients who receive bridging have a higher risk of bleeding than stroke, which is in contrast to some physicians’ experience and current recommendations.
A physician caring for a patient who’s had a stroke may be inclined to recommend bridging despite the lack of efficacy and evidence of bleeding risk. Additionally, until guidelines reflect the most current research, physicians may be reluctant to provide care in contrast to these recommendations.
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.