Edoxaban ENSUREs effective cardioversion in non-valvular atrial fibrillation
medwireNews: Edoxaban appears to be an effective alternative to warfarin and enoxaparin bridging for cardioversion of patients with non-valvular atrial fibrillation, findings from a phase IIIb trial show.
“The occurrence of major and CRNM [clinically relevant non-major] bleeding and thromboembolism was low in the two treatment groups, irrespective of a TEE [transoesophageal echocardiography]-guided strategy or whether patients were warfarin naïve”, the team reports in The Lancet.
They add that the low rates were achieved against “exceptionally well controlled warfarin”, with the time in the therapeutic range on warfarin being more than 70% and adherence to edoxaban was “excellent” with more than 99% compliance.
In a related editorial, Alexandros Briasoulis (Mayo Clinic, Rochester, Minnesota, USA) and Luis Afonso (Wayne State University, Detroit, Michigan, USA) point out that the main practical advantage of non-vitamin K antagonist oral anticoagulants (NOACs) such as edoxaban, compared with warfarin, are “their rapid onset of action and reliable anticoagulation properties, allowing for treatment initiation just hours before cardioversion when a TEE-guided approach is selected without the need to switch anticoagulants.”
The ENSURE-AF (Edoxaban versus enoxaparin–warfarin in patients undergoing cardioversion of atrial fibrillation) trial, carried out across multiple centres in 19 countries compared edoxaban 60 mg/day with standard enoxaparin–warfarin treatment in a moderately high-risk group of 2199 patients aged an average of 64 years.
Due to warfarin being well controlled, the median time from randomisation to cardioversion was the same in both treatment groups, at 2 hours for patients assigned to a TEE-guided strategy and 23 days for those assigned to a non-TEE-guided strategy.
At the end of 8 weeks, the composite primary efficacy endpoint of stroke, systemic embolic event, myocardial infarction or cardiovascular mortality had occurred in five (<1.0%) of the 1095 edoxaban-treated patients in the intention-to-treat analysis and 11 (1%) of the 1104 patients in the enoxaparin–warfarin group.
The main difference between the two groups was for cardiovascular mortality, which occurred in 0.1% of patients in the edoxaban group versus 0.5% of those in the enoxaparin–warfarin group.
Cardioversion success rates were also similar, at 78% in the edoxaban group and 80% in the enoxaparin–warfarin group.
In terms of safety, the endpoint was combined major and CRNM bleeding events from treatment initiation up to 30 days, which occurred in 16 (1%) of 1067 patients in the edoxaban group and 11 (1%) of 1082 in the enoxaparin–warfarin group.
The researchers, led by Andreas Goette (St Vincenz-Hospital, Paderborn, Germany), report that both efficacy and safety event rates were similar regardless of TEE strategy and prior anticoagulation status. And outcomes were comparable across a variety of patient groups, including patients with high creatine clearance (≥80 mL/min) and those who received a reduced edoxaban dose of 30 mg/day due to having a creatinine clearance of 15–50 mL/min, a low bodyweight of up to 60 kg or taking concomitant P-glycoprotein inhibitors.
However, Briasoulis and Afonso caution that although the trial was large, low event rates in both treatment groups meant it was not statistically powered to show differences in safety and efficacy endpoints across subgroups.
Further trial information is needed and will be provided by the ongoing EMANATE trial, they say. “In the meantime, NOACs can be safely used in clinical practice to prevent thromboembolic events in patients with atrial fibrillation undergoing elective cardioversion”, they conclude.
By Lucy Piper
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