Dabigatran is a reasonable alternative to warfarin in patients with atrial fibrillation (AF) requiring cardioversion, according to a new subanalysis of the RE-LY trial published online on Jan. 3 in Circulation.
Cardioversion (both electric and pharmacological) in patients with AF is associated with an increased risk of thromboembolic events. AF patients are generally prescribed warfarin to reduce the risk of stroke.
Dabigatran (Pradaxa, Boehringer Ingelheim), recently approved the by the FDA, is a reversible direct thrombin inhibitor, with a rapid onset of action and a half-life of 12 to 17 hours, making it an attractive alternative to warfarin.
In the RE-LY trial, dabigatran at 110 mg dose (D110) was similar to warfarin for the prevention of thromboembolism and stroke, and dabigatran at 150 mg dose (D150) was superior to warfarin. However, the efficacy and safety of dabigatran in the setting of cardioversion had been uncertain.
In RE-LY, cardioversion on randomized treatment was permitted and precardioversion transesophageal echocardiography (TEE) was encouraged, particularly in dabigatran-assigned patients.
Rangadham Nagarakanti, MD, from Louisiana State University School of Medicine in New Orleans, and colleagues found that 1,983 cardioversions were performed in 1,270 patients: 647 in D110, 672 in D150 and 664 in the warfarin group.
TEE was performed prior to cardioversion in more patients in the dabigatran arms than in those receiving warfarin: 25.5 percent D110, 24.1 percent D150 and 13.3 percent warfarin, of which 1.8, 1.2, and 1.1 percent, respectively, were positive for left atrial thrombi.
Investigators said the difference in TEE use "might be attributable to study guidance or investigator preference for cardioverting with prior TEE on an experimental therapy, in this case, dabigatran [which was not FDA approved at the time of the trial]."
Continuous treatment with dabigatran for three weeks before cardioversion was lower in D110 (76.4 percent) and D150 (79.2 percent) compared with warfarin (85.5 percent).
Rates of stroke and systemic embolism within 30 days of cardioversion were low and did not differ significantly between treatment arms: 0.8, 0.3 and 0.6 percent, respectively, though the RE-LY trial and this subgroup analysis were not powered to demonstrate statistical significance.
Similarly, major bleeding within 30 days of cardioversion was infrequent and comparable between treatment groups: 1.7, 0.6 and 0.6, respectively, and there were no major differences between those who underwent TEE and those who did not.
Nagarakanti et al noted that the major drawbacks of warfarin in the setting of cardioversion are its "delayed onset of action and the need for heparin infusion or low-molecular-weight heparin as bridging therapy if the patient's international normalized ratio is not in the therapeutic range or the patient is new to vitamin K antagonists."
Subsequently, the advantage of dabigatran is that it "achieves therapeutic blood levels within two hours and steady-state concentration in two to three days after twice-daily administration. Therefore, "it has the advantage of being more suitable for outpatient management, and its use may prove economical by avoiding hospitalization.
"The RE-LY trial confirmed the efficacy and safety of warfarin in cardioversion in a large cohort of warfarin-treated patients," the researchers concluded. "It also allowed comparison with the new oral anticoagulant dabigatran. The results show that the two drugs are comparable in this setting."