The label update 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 LIXIANA with enoxaparin/warfarin with a median time in therapeutic range (INR 2-3) of 70.8 %.
These data support the use of LIXIANA as an effective and safe alternative to the best possible conventional treatment with enoxaparin and warfarin. LIXIANA's rapid onset of action allows for prompt cardioversion in the TEE-guided approach as early as two hours after LIXIANA intake, helping to avoid delays or postponements of the procedure.
"ENSURE-AF provides important insight into the use of LIXIANA 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 LIXIANA 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 LIXIANA in different clinical settings, through studies such as ENSURE-AF."
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.
Initial treatment with enoxaparin (followed by overlapping VKA treatment) until the VKA reaches the therapeutic range of INR 2-3, represents the best possible conventional treatment.
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 LIXIANA 60/30 mg 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 LIXIANA 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 LIXIANA and exceptionally well-controlled warfarin arms. There was no difference between the TEE-guided approach and the delayed cardioversion setting.
These data support the use of LIXIANA as an effective and safe alternative to the best possible conventional treatment with enoxaparin and warfarin, and allow for prompt cardioversion in the TEE-guided approach as early as two hours after LIXIANA intake.
This label update makes LIXIANA the only NOAC with specific label guidance for early cardioversion within two hours after LIXIANA intake in the TEE-guided approach.