From Pages to Practice

By Rachel Wolfson, M.D., Ph.D.

Published April 26, 2017

We hear it every morning on rounds: “Mr. Jones is a 56-year-old gentleman with atrial fibrillation, on anticoagulation with warfarin, recent INR of 2.6...” The use of warfarin, a blood thinner that acts as an antagonist of vitamin K, has been the standard of care for decades in patients with atrial fibrillation. Although warfarin has prevented countless strokes and other thromboembolic complications, it is also associated with very serious bleeding complications. The process of anticoagulation is, of course, a delicate balance, and one of the advantages of warfarin is that it can be rapidly reversed with vitamin K and fresh frozen plasma in the event of a severe bleed.

About 10 years ago, non-vitamin K antagonist oral anticoagulants emerged as a treatment option. Dabigatran, for example, acts as a direct thrombin inhibitor. At first, the non-vitamin K antagonist oral anticoagulants were at a disadvantage, when compared to warfarin, because they were irreversible. However, more recently, drugs such as idarucizumab, a monoclonal antibody that binds dabigatran and a potent reversal agent for dabigatran, are available for patients with severe bleeds on dabigatran. With two classes of anticoagulants with effective antidotes, the question emerges: Which one should we use when?

In this week’s issue of NEJM, the RE-CIRCUIT trial addressed one aspect of this question in a randomized-controlled, open-label trial in 704 patients with nonvalvular atrial fibrillation who were undergoing ablation of atrial fibrillation. Patients were randomized to receive uninterrupted anticoagulation with either warfarin or dabigatran beginning 4 to 8 weeks before ablation and continued for 8 weeks after the procedure.

The incidence of major bleeding events, the primary outcome, was lower with dabigatran than with warfarin treatment (5 vs. 22 patients; 1.6% vs. 6.9%; P<0.001). Rates of minor bleeding events were similar in the two groups. Only one patient in the warfarin group had a thromboembolic event.

These results indicate that anticoagulation with dabigatran is associated with fewer major bleeding events than warfarin in patients receiving ablation for atrial fibrillation. Although the major endpoints in the trial were adjudicated blindly, the results are limited by the open-label design and possible confounding. Further, power calculations indicated a prohibitive sample size for a formal test of noninferiority.

More studies are needed to understand the benefits and risks of different classes of anticoagulation in various clinical contexts. For now, if Mr. Jones is undergoing atrial fibrillation ablation, management with dabigatran instead of warfarin might lower his risk of severe bleeding episodes.

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Rachel is a fifth-year MD/PhD student at Harvard Medical School. She is originally from Okemos, MI, and graduated from Stanford University in 2011. For her PhD research, she is studying the regulation of cell growth in response to nutrients.