Results of the X-VERT trial, presented at the European Society of Cardiology meeting (ESC; 30 August–3 September, Barcelona, Spain), showed that rivaroxaban (Bayer/Janssen Pharmaceuticals) appears to be an effective and safe alternative to vitamin K antagonist (VKA) therapy in patients with non-valvular atrial fibrillation who are undergoing elective cardioversion (electrical or pharmacological). Now, a new and larger study (ENSURE-AF), which is evaluating the efficacy and safety of edoxaban (Daiichi Sankyo) compared with enoxaparin/warfarin in patients with non-valvular atrial fibrillation undergoing electrical cardioversion is on its way. Andreas Goette (St Vincenz-Hospital Paderborn, Germany) principal investigator of ENSURE-AF speaks to Cardiac Rhythm News on the details of this trial.
ENSURE-AF (Edoxaban vs. warfarin in subjects undergoing cardioversion of atrial fibrillation) is a multinational, prospective, randomised, open-label, blinded endpoint evaluation parallel group study, which will evaluate the efficacy and safety of the investigational oral, once-daily direct factor Xa-inhibitor edoxaban compared to enoxaparin/warfarin for the prevention of stroke and other blood clot complications in patients with non-valvular atrial fibrillation undergoing electrical cardioversion.
Patients will be randomised to receive edoxaban 60mg (or a patient specific dose of edoxaban 30mg for patients with renal impairment or low body weight or p-glycoprotein inhibitor use) or enoxaparin/warfarin for 28-49 days. In the trial, patients will be stratified with regard to the use of transesophageal echocardiography.
What is the rationale to undertake a trial like ENSURE-AF?
Cardioversion of atrial fibrillation is performed all over the world as an initial attempt to restore sinus rhythm in a large proportion of atrial fibrillation patients. However, after this procedure most patients need oral anticoagulation for at least four weeks after successful cardioversion. Thus, novel oral anticoagulant therapy appears to be very convenient for patients, because they can be fully anticoagulated within two-four hours with not need to overlap heparin therapy with warfarin. The ENSURE-AF trial is the largest prospective cardioversion trial ever. The trial is powered to assess the safety for the use of 60mg edoxaban once daily in comparison to warfarin in the setting of electrical cardioversion. So far, no other trial was adequately powered to assess safety or efficacy in this clinical context. Therefore, the results of the trial will have the potential to have an impact on the existent atrial fibrillation guidelines.
Has ENSURE-AF started enrolling patients?
The trial started enrolling patients in May 2014. Recruitment is expected to be completed in 2015. More than 2,200 patients are expected to be enrolled in more than 300 clinical sites worldwide.
Could you please explain the differences of ENSURE-AF and X-VERT?
There are several differences between the two trials. The X-VERT trial assessed the use of rivaroxaban in the setting of electrical and pharmacological cardioversion. Furthermore, a TEE-guided and non-TEE-guided approach were allowed in the trial. Overall, the different subgroups were small, and therefore, the trial was not powered to assess the safety or efficacy of the different treatment strategies. In contrast, the ENSURE-AF trial allows electrical cardioversion only. Similar to the X-VERT trial, a TEE-guided and non-TEE-guided approach is also allowed in the ENSURE-AF trial. With more than 2,200 patients the trial is adequately powered to assess the safety of edoxaban therapy in comparison to warfarin in this clinical scenario.
Are there any other trials exploring new oral anticoagulants in this setting?
There are retrospective data for the use of dabigatran (Pradaxa, Boehringer Ingelheim) in patients undergoing cardioversion in the RE-LY trial. In addition, there are also retrospective data for the use of apixaban (Eliquis, Bristol Myers Squibb/Pfizer) in cardioversion performed in the ARISTOTLE trial. To the best of knowledge, a prospective randomised trial using apixaban in patients undergoing cardioversion is planned.