Edoxaban Shows Safety, Efficacy for A-fib Patients Undergoing Cardioversion: ENSURE-AF
ROME, Italy—ENSURE-AF, the largest randomized trial of anticoagulation for patients undergoing electrical cardioversion for nonvalvular A-fib, has shown that both edoxaban and traditional treatment with warfarin plus as-needed enoxaparin provide low and similar rates of ischemic and bleeding outcomes.
The net clinical outcome—a composite of stroke, systemic embolic events, MI, cardiovascular mortality, and major bleeding—tended to favor edoxaban (Savaysa; Daiichi Sankyo), although the difference was not significant (0.7% vs 1.4%; OR 0.50; 95% CI 0.19-1.25), Andreas Goette, MD (St. Vincenz-Hospital, Paderborn, Germany), reported at the European Society of Cardiology Congress 2016. The findings were published simultaneously online in the Lancet.
“Edoxaban appears to be an effective and safe alternative in this scenario . . . and it allows, actually, a very rapid onset of cardioversion after 2 hours of the first administration of [the drug]” when guidance with transesophageal echocardiography (TEE) is used, Goette said.
Speaking with TCTMD, Paulus Kirchhof, MD (University of Birmingham, England), who chaired the task force behind the recently updated European A-fib guidelines, said the trial “is an important confirmation of the safety of NOACs [non-vitamin K antagonist oral anticoagulants] in the setting of cardioversion.”
He said it also confirms advice found in both US and European guidelines, which recommend anticoagulation for at least 3 weeks before cardioversion and at least 4 weeks after the procedure with no preference given to either NOACs or vitamin K antagonists.
In clinical practice, NOACs can be easier to use because they do not require the regular blood tests that come with warfarin therapy, Kirchhof said. He added that there is evidence from the X-VERT study that the time to cardioversion is shorter when a NOAC is used because of the shorter onset time and higher stability of the treatment.
One important consideration for clinical practice, he said, is the need to confirm that NOAC-treated patients are actually taking their medication before performing cardioversion. Most centers, have already started employing pill counts, which—in a way—is a substitute for measuring INR levels in patients taking vitamin K antagonists, he said.
Low Event Rates All Around
ENSURE-AF included 2,199 patients enrolled at 239 sites in the United States and Europe. Patients were divided into two groups based on whether their treating physicians used a TEE-guided anticoagulation strategy and were then randomized to once-daily edoxaban 60 mg (or 30 mg if they had poor kidney function, low body weight, or used a P-glycoprotein inhibitor) or warfarin plus enoxaparin. Enoxaparin was only given if the INR was below 2.0.
At 28 days, the rate of the primary efficacy outcome (stroke, systemic embolic events, MI, or cardiovascular mortality) was very low in both the edoxaban and control groups (0.5% vs 1.0%; OR 0.46; 95% 0.12-1.43).
In terms of safety, there were no differences between groups for any of the bleeding outcomes. Any bleeding occurred in 3.0% of the edoxaban-treated patients and 3.2% of the controls (OR 0.93; 95% CI 0.55-1.55).
The findings were similar regardless of whether a TEE-guided strategy was employed.
Asked whether the findings could be applied to all NOACs, Kirchhof said, “What we have seen in the published meta-analyses on the NOACs in general stroke prevention is that they can probably be regarded as a class and that there are many more similarities between them than there are differences.”
Goette A, Merino JL, Ezekowitz MD, et al. Edoxaban versus enoxaparin-warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial. Lancet. 2016;Epub ahead of print.
- The study was supported by Daiichi Sankyo.
- Goette reports serving as a consultant for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer and as a speaker for AstraZeneca, Bayer, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Pfizer, and Sanofi-Aventis.
- Kirchhof reports multiple relationships with industry.