Venous thromboembolism (VTE): New analysis shows maintained efficacy and safety of LIXIANA

Daiichi Sankyo Europe GmbH (hereafter Daiichi Sankyo) has announced data from a new analysis of the phase 3 Hokusai-VTE study, which showed that a reduced dose of LIXIANA® (edoxaban, once-daily 30 mg) was as effective and well-tolerated in preventing recurrent VTE episodes as the standard 60 mg edoxaban treatment regimen, and safer than warfarin in preventing bleeding events in patients meeting the criteria for dose reduction.^1,2

Hokusai-VTE, the largest single comparative trial of a NOAC in patients with VTE to date, was a randomised, double-blind trial of 8,292 patients with acute VTE.2 In the Hokusai-VTE trial, patients with a creatinine clearance of 30-50 ml/minute, body weight ≤ 60 kg or receiving certain P-glycoprotein inhibitors were given a reduced dose of 30 mg edoxaban once daily. Of those patients that qualified for dose reduction, 733 were randomised to receive the reduced 30 mg edoxaban dose and 719 received a matching dose of warfarin.¹ Patients receiving standard treatment regimens, 3,385 were treated with 60 mg edoxaban and 3,403 treated with warfarin, adjusted to maintain the international normalised ratio between 2.0 and 3.0.¹

This new analysis, published in the peer-reviewed journal Thrombosis and Haemostasis, found that the reduced edoxaban 30 mg dose resulted in lower blood levels of edoxaban, but preserved efficacy against recurrent VTE in dose reduced patients compared to patients that received the full 60 mg edoxaban dose (Hazard Ratio [HR]=0.96; 95 % Confidence Interval [CI]: 0.61-1.52).¹ Dose reduced patients also had fewer clinically relevant bleeds, a key adverse event, compared to similar patients taking warfarin (7.9% vs 12.8% HR=0.62; 95 % CI: 0.44-0.86; p < 0.01 for superiority).¹

"The Hokusai-VTE study identified higher bleeding rates in warfarin-treated patients who met the criteria for dose reduction compared to those that did not, indicating that there is a sub-set of patients who could benefit from a safer therapy," said Dr Peter Verhamme, Associate Professor of Cardiology at KU Leuven, Belgium and lead author of the new analysis. "It is therefore reassuring to see that a reduced dose of once-daily edoxaban offers an alternative to those patients treated with warfarin who meet the criteria for dose reduction, with an enhanced safety profile."

VTE is the formation of blood clots in the vein and is a potentially fatal condition.3 VTE is the collective term for pulmonary embolism (PE) and deep-vein thrombosis (DVT) and represents a major health problem in the EU, with over 1.5 million VTE events in Europe every year.⁴ Incidence is also seen to be rising with the ageing population.¹ Anticoagulant therapy, such as edoxaban, helps to prevent blood clots from forming and can help prevent thromboembolic events.¹

"We welcome this sub-analysis of the Hokusai-VTE study, which builds on the existing wealth of data on edoxaban and supports the understanding of different treatment strategies for patients with VTE," said Oliver Appelhans, Senior Vice President, Head of Cardiovascular Products, Business Development & NPP at Daiichi Sankyo Europe GmbH.

About the Hokusai-VTE Study

The Hokusai-VTE global phase 3 study was the largest single comparative trial of a NOAC in patients with VTE, which evaluated once-daily edoxaban versus warfarin in 8,292 patients with either acute symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE) or both. The Hokusai-VTE study was designed to reflect clinical practice using a flexible treatment duration of 3-12 months in a broad spectrum of VTE patients, including initial use of parenteral anticoagulant (heparin) for at least five days, the proven global standard of care. Edoxaban demonstrated non-inferiority to warfarin for the primary efficacy endpoint of recurrence of symptomatic VTE, and was found to be superior in the primary safety endpoint of clinically relevant bleeding compared to warfarin.²

Article: Dose reduction of edoxaban preserves efficacy and safety for the treatment of venous thromboembolism, P. Verhamme et al., Thrombosis and Haemostasis, doi: 10.1160/TH16-03-0244, published online 21 July 2016.