Performing Cardioversion: Dabigatran Therapy vs. Warfarin
Abstract & Commentary
By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, CharlottesvilleDr. DiMarco does research for Medtronic, is a consultant for Medtronic, Novartis, and St. Jude, and is a speaker for Boston Scientific.
Source: Nagarakanti R, et.al. Dabigatran versus warfarin in patients with atrial fibrillation: An analysis of patients undergoing cardioversion. Circulation. 2011;123:131-136.
The randomized evaluation of long-term anticoagulation Therapy (RE-LY) trial was a study that compared two doses of a new direct-thrombin inhibitor, dabigatran, to warfarin for stroke prevention in patients with atrial fibrillation. In this paper, the investigators report the experience with dabigatran and warfarin in patients in RE-LY who underwent cardioversion. In RE-LY, patients were randomized to one of two doses of dabigatran (110 mg or 150 mg bid; D110 and D150 groups) or warfarin. Data on cardioversions were collected during the trial. In this study, it was recommended that the assigned study drug (either dabigatran or warfarin) be continued during cardioversion. A pre-cardioversion transesophageal echo (TEE) was encouraged if the cardioversion was planned within the first 60 days after randomization. Decisions concerning additional antithrombotic agents, or the need for a TEE, were the responsibility of the patient's primary cardiologist. When a cardioversion took place, data were collected concerning pre- and post-procedure antithrombotic therapy, details of the anticoagulants used, and the method of cardioversion. TEE data, if available, were also collected. Stroke and systemic embolism and major bleeding episodes within 30 days of the cardioversion were the major outcome measures.
RE-LY enrolled 18,113 patients. During the course of the trial, 1,983 cardioversions were performed in 1,270 patients. There were 647,672, and 664 cardioversions in the D110, D150, and warfarin groups, respectively. Approximately 80% of the cardioversions were performed when the protocol's assigned study drug had been taken for at least three weeks before the cardioversion. Eighty-five to 95% of patients were continued on protocol-assigned study drugs before and after the cardioversion.
Transesophageal echocardiograms were performed before cardioversion more often in patients assigned to dabigatran than in those who received warfarin (25% vs. 13%). Among those who underwent TEE, there was no difference in the incidence of left atrial spontaneous contrast (21%, 27%, 32%) in the D110, D150 and warfarin groups, respectively, or left atrial appendage thrombus (1.8%, 1.2%, and 1.1%, respectively). Slightly more than 80% of all cardioversions were electrical, with the remainder being classified as pharmacologic. Eighty-eight percent of all cardioversions were successful, with normal sinus rhythm being restored.
The stroke and systemic embolic event rates within 30 days after cardioversion were low in all three groups (0.77%, 0.30%, and 0.60% in the D110, D150 and warfarin groups, respectively). The stroke and systemic embolism rates were similar in patients with and without pre-procedure TEEs. Major bleeding was infrequent in all groups (1.7%, 0.6%, and 0.6% in the D110, D150 and the warfarin groups, respectively).
The authors conclude that the RE-LY trial shows that both dabigatran and warfarin, used according to the guidelines in the trial, are effective in reducing the expected incidence of stroke and systemic emboli after cardioversion in patients with atrial fibrillation.
Dabigatran is a new antithrombotic agent that has now been released in the United States. Dabigatran does not have many of the drug and food interactions that make treatment with warfarin so difficult. A single dose is used in patients with preserved renal function, and patients do not require INR monitoring. The RE-LY study enrolled over 18,000 patients and followed them for several years. As might be expected, during the course of the study, a significant number of cardioversions (over 1,900) were performed. This constitutes the largest cardioversion experience in a randomized trial that I am aware of. Although this was not a primary endpoint of the study, both doses of dabigatran seem to be as effective as warfarin in reducing the incidence of stroke and systemic embolism after cardioversion. The low incidence with all three agents suggests that there will never be a randomized trial comparing the effects of dabigatran and a standard warfarin regimen at the time of cardioversion. However, the results are such that physicians can proceed with cardioversions in patients receiving dabigatran as long as they are sure the patients have been compliant with therapy.