The European Committee for Medicinal Products for Human Use (CHMP) has recommended approval of a label update for the oral, once-daily direct factor Xa-inhibitor edoxaban (Lixiana), to provide guidance on its use in patients undergoing transoesophageal echocardiography (TEE)-guided and delayed cardioversion.
This label update makes edoxaban the only non-vitamin K oral anticoagulant (NOAC) with specific label guidance for early cardioversion within two hours after edoxaban intake in the TEE-guided approach.
Cardioversion is a procedure used to restore normal, regular heart rhythm in AF patients. Due to an associated risk of thrombotic events such as stroke, guidelines recommend anticoagulation before and after the procedure. The delayed onset of action and fluctuations in INR associated with VKA treatments such as warfarin, can result in costly and inconvenient delays to cardioversion in patients.
The CHMP decision is based on results from the ENSURE-AF study, the largest, prospective randomised clinical trial of an anticoagulant for cardioversion in patients with NVAF. The study enrolled 2,199 patients, and compared once-daily edoxaban with enoxaparin/warfarin with a median time in therapeutic range (INR 2-3) of 70.8%.
These data support the use of edoxaban as an effective and well tolerated alternative to the best possible conventional clinical optimal treatment with enoxaparin and warfarin. Edoxaban’s rapid onset of action allows for prompt cardioversion in the TEE-guided approach as early as two hours after edoxaban intake, helping to avoid delays or postponements of the procedure.
“ENSURE-AF provides important insight into the use of edoxaban in the setting of TEE-guided and delayed cardioversion in NVAF patients,” said Wolfgang Zierhut, MD, Executive Director, EU Cardiovascular Medical Affairs. “We are pleased that the CHMP has recognised the importance of the ENSURE-AF data for edoxaban in this common procedure, by recommending this label update. Daiichi Sankyo is committed to supporting patients and physicians by advancing understanding of the efficacy and safety of edoxaban in different clinical settings, through studies such as ENSURE-AF.”
The primary efficacy endpoint of the ENSURE AF study was a composite of stroke, systemic embolic events, myocardial infarction and cardiovascular mortality, which occurred in five patients in the edoxaban 60/30mg arm versus 11 in the enoxaparin-warfarin arm. The primary safety endpoint was major and clinically relevant non-major bleedings (CRNM), which occurred in 16 patients in the edoxaban arm versus 11 patients in the enoxaparin-warfarin arm. The difference between the treatment arms was statistically non-significant.
Event rates of thromboembolism and major and CRNM bleedings were low in the edoxaban and exceptionally well-controlled warfarin arms. There was no difference between the TEE-guided approach and the delayed cardioversion setting.