Peri-Procedural Bleeding and Thromboembolic Events With Dabigatran Compared to Warfarin: Results From the RE-LY Randomized Trial

Study Questions:

When patients anticoagulated for stroke prevention in atrial fibrillation undergo surgery or invasive procedures, what is the periprocedural risk of bleeding and thromboembolic events associated with dabigatran compared to warfarin?


The authors reported a re-analysis of the RE-LY study, a randomized, prospective study of dabigatran 110 mg twice daily, versus dabigatran 150 mg twice daily versus warfarin for stroke prevention in atrial fibrillation. For all subjects in that study who underwent invasive procedures or surgery, bleeding rates were evaluated 7 days prior until 30 days following the first such procedure for each subject. During the initial 3 years of the study, dabigatran was held 24 hours prior to any procedure or surgery in all patients. During the last 8 months of the study, dabigatran was discontinued 24 hours prior to surgery or procedures deemed to be low risk for bleeding, and 2-5 days prior to surgery or procedures deemed to be associated with high risk of bleeding, depending on renal function. Bleeding rates were compared among treatment groups for the current study.


During the course of this study, 4,591 subjects underwent at least one invasive procedure, in similar numbers among the three treatment groups (24.7% in the dabigatran-110 group; 25.4% in the dabigatran-150 group; and 25.9% in the warfarin group, p = 0.34). Subjects in the dabigatran groups received study drug 49 (35-85) hours preprocedure, compared to 114 (87-144) hours in the warfarin group (p < 0.001). There were no significant differences in periprocedural bleeding rates (3.8%, 5.1%, and 4.6%, for the dabigatran-110, dabigatran-150, and warfarin groups, respectively, relative risk [RR], 0.83; 95% confidence interval [CI], 0.59-1.17; p = 0.28 for dabigatran-110 vs. warfarin, and RR, 1.09; 95% CI, 0.80-1.49 p = 0.58 for dabigatran-150 vs. warfarin). Among patients undergoing urgent surgery, major bleeding rates again did not differ (17.8%, 17.7%, and 21.6%, for the dabigatran-110 dabigatran-150, and warfarin groups, respectively, RR, 0.82; 95% CI, 0.48-1.41; p = 0.47 for dabigatran-110 vs. warfarin; and RR, 0.82; 95% CI, 0.50-1.35; p = 0.44, for dabigatran-150 vs. warfarin).


The authors concluded that dabigatran and warfarin were associated with similar rates of periprocedural bleeding, including patients having urgent surgery. The authors further observed that dabigatran facilitated a shorter interruption of oral anticoagulation.


The original RE-LY study was very encouraging, suggesting that the higher dose of dabigatran versus warfarin in patients with atrial fibrillation was superior with lower stroke rate and no greater bleeding risk. (The bleeding risk was actually lower, although stroke risk was similar with the lower dose of dabigatran versus warfain). Given the differences in half-life between the agents, and the lack of a reversal agent for dabigatran, there has been great concern about the safety of interrupting anticoagulation for invasive procedures or surgery. The current report suggests that, in the context of this highly controlled clinical trial, there was no increase of periprocedural bleeding seen in patients with atrial fibrillation treated with dabigatran versus warfarin. The real-world experience has yet to be evaluated, especially in the setting of unanticipated urgent procedures or trauma. (It should be noted that the number of subjects undergoing urgent surgery in the current report was quite small). The lack of any clear reversal agent may make the urgent interruption of anticoagulation with dabigatran problematic. We await real-world observational data to further shed light on this topic.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Atrial Fibrillation/Supraventricular Arrhythmias, Novel Agents

Keywords: Stroke, Warfarin, Transcription Factors, beta-Alanine, Benzimidazoles, Half-Life, Cardiology, Embolism, Confidence Intervals, Hemorrhage, Atrial Flutter

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