EMANATE: Another NOAC Shown to Be Safe, Effective in the Setting of Cardioversion for A-fib

BARCELONA, Spain—Apixaban appears to be an effective and safe alternative to heparin plus a vitamin K antagonist (VKA) for patients with A-fib who are undergoing rapid cardioversion and require anticoagulation, the 1,500-patient EMANATE trial shows.

There were no strokes in apixaban-treated patients versus six in those receiving the heparin/VKA combination (P = 0.0164), with no systemic embolic events in either group, Michael Ezekowitz, MD (Lankenau Medical Center, Wynnewood, PA), reported last week at the European Society of Cardiology Congress 2017.

Apixaban resulted in fewer major bleeds (three vs six) and clinically relevant nonmajor bleeds (11 vs 13). Two patients died in the apixaban arm, and one died in the heparin/VKA group.

“We believe that the findings observed in EMANATE support the use of apixaban in patients with atrial fibrillation undergoing cardioversion,” Ezekowitz said during his presentation.

The low event rates and comparable safety and efficacy seen in the trial are consistent with prior analyses of pivotal trials of non-VKA oral anticoagulants (NOACs), as well as results from the X-VeRT and ENSURE-AF trials, dedicated studies looking at use of rivaroxaban (Xarelto; Janssen/Bayer) and edoxaban (Savaysa; Daiichi-Sankyo), respectively, in the setting of cardioversion.

“I think practitioners have been looking for answers that would help them with patients, especially those that go on to rapid cardioversion within 48 hours,” commented C. Michael Valentine, MD (Centra Health, Lynchburg, VA), who was not involved in the study.

Taking EMANATE and the prior studies into consideration, Valentine, vice president of the American College of Cardiology, added that he would feel comfortable using a NOAC in this setting. The advantages of using one of those agents instead of heparin/VKA, especially when a patient can be sent to cardioversion within just a few hours of administering a loading dose in the office, would be “ease of use, expense, and safety,” he told TCTMD.

Lessons in Thrombus Resolution

EMANATE included 1,500 patients with A-fib who had been treated with less than 48 hours of anticoagulation (61% had not received any anticoagulation before randomization). They were randomized to apixaban 5.0 mg twice daily or heparin/VKA.

At their discretion, treating physicians were allowed to administer a 10-mg loading dose of apixaban (or 5 mg if certain high-risk features were present); cardioversion could be performed 2 hours later in those cases. Efficacy and safety appeared to be similar in the overall apixaban arm and in those who received a loading dose.

The trial investigators also wanted to evaluate how imaging might guide cardioversion decision-making. Of 840 patients imaged, 61 had thrombus in the left atrial appendage, which precluded immediate cardioversion. These patients continued on their assigned anticoagulation regimen and underwent repeat imaging an average of 37 days later. At that time, the thrombus was resolved in 52% of patients receiving apixaban and 56% receiving heparin/VKA.

Valentine said he was surprised at such a low rate of resolution, noting that some physicians would not bother with repeat imaging to confirm resolution of the thrombus before cardioverting. “I think it’s a warning sign to practitioners that if imaging does show evidence of thrombus then you’ve got to look again,” he said.

No Firm Conclusions

Serving as a discussant following Ezekowitz’s presentation, Jens Cosedis Nielsen, MD, DMSc (Aarhus University Hospital, Denmark), said, “I think that the randomized trials—here EMANATE—comparing NOACs to VKA provide us with very important data on the outcomes around cardioversion for both these treatments.”

But he raised several issues to consider when interpreting the EMANATE results. He pointed out that there was no prespecified primary endpoint, the trial was underpowered, and—when considering death—there was no difference in clinical outcomes between arms. The low event rates and comparable safety and efficacy are consistent with a recent meta-analysis looking at the use of NOACs in cardioversion, Nielsen pointed out.

The infrequent occurrence of events, however, “means that any statistical comparisons should be interpreted very cautiously,” he said, adding that the issues he discussed regarding EMANATE “preclude us from taking any hard conclusion from this trial.”

Nonetheless, Nielsen concluded, “I think that EMANATE adds to the growing evidence suggesting that NOACs are a viable alternative to heparin therapy in patients undergoing cardioversion for AF.”