Despite concerns of bleeding with dabigatran, a substudy published online June 14 in Circulation of the RE-LY trial found the drug had comparable rates of peri-operative bleeding and thrombotic complications when compared with warfarin. Additionally, researchers found that the subset of patients receiving dabigatran were four times more likely to have the procedure done within 48 hours of stopping anticoagulation.
“The RE-LY trial demonstrated that dabigatran is well-tolerated and that compared to warfarin, dabigatran 150 BID is more effective at preventing stroke and systemic embolism with a similar risk of major bleeding, while dabigatran 110 BID is associated with a lower risk of major bleeding and a similar rate of stroke and systemic embolism,” Jeff S. Healey, MD, MSc, of McMaster University in Hamilton in Canada, and colleagues wrote.
“However, as the anticoagulant effect of dabigatran is currently difficult to precisely measure and the drug does not yet have a specific antidote, there is concern that dabigatran may increase the risk of bleeding in patients undergoing invasive procedures, particularly if performed on an emergency basis.”
To study the bleeding risks associated with dabigatran (Pradaxa, Boehringer Ingelheim) during invasive procedures, Healey et al used RE-LY trial data to assess the peri-procedural bleeding risks in 4,591 patients undergoing at least one invasive procedure.
Of these 4,591 patients, 24.7 percent received 110 mg of dabigatran, 25.4 percent received a 150 mg dose of dabigatran and 25.9 percent received warfarin. The procedures included: pacemaker/defibrillator implantation (10.3 percent), dental procedures (10 percent), diagnostic procedures (10 percent), cataract removal (9.3 percent), colonoscopy (8.6 percent) and joint replacement (6.2 percent).
Patients who received dabigatran had the last dose given 49 hours prior to procedure; warfarin patients received the last dose 114 hours prior to procedure.
The researchers found no significant differences in the peri-procedural bleeding rates between those receiving 110 mg of dabigatran, 150 mg of dabigatran or warfarin, 3.8 percent, 5.1 percent and 4.6 percent, respectively.
Bleeding complications occurred in 17.8 percent of patients who underwent urgent treatment and were administered 110 mg of dabigatran compared with 17.7 percent who received 150 mg of dabigatran and 21.6 percent who received warfarin.
Of the patients on wafarin, 7.1 percent of surgeries were classified as urgent compared with 4.2 percent of patients assigned to the 110 mg of dabigatran and 9.1 percent of patients administered the 150 mg dose of the drug.
“Compared to those having elective surgery, the incidence of major bleeding for patients in each treatment arm who had urgent surgery were five to six-fold higher,” the researchers wrote. The risk of ischemic stroke or embolism was also four times greater among patients who underwent urgent surgery.
The researchers said that the findings are “reassuring, given the lack of a widely available test to precisely measure the anticoagulant effect of dabigatran and the lack of a direct reversing agent and the concern that dabigatran may increase the risk of bleeding complications related to surgery or procedures, especially those that are urgent.”
Additionally, the authors called the fact that dabigatran has a short half-life a key advantage in terms of being able to discontinue the therapy 24 to 48 hours prior to a procedure, which in turn can reduce the risk of thromboembolic complications. They also said that this cuts down the costs and complications often associated with heparin bridging strategies.
“In RE-LY, nearly half of all patients treated with dabigatran had surgery within 48 hours of stopping oral anticoagulation; a rate more than four times higher than among patients receiving warfarin,” the authors summed.
“When surgery or a procedure was performed during these short periods, dabigatran-treated patients had a substantially lower rate of major bleeding compared to those receiving warfarin, although this is likely explained by the higher proportion of non-urgent surgery that was completed in dabigatran-treated patients.”