Daiichi Sankyo Reports Non-Inferiority in Lixiana Clinical Trial for Atrial Fibrillation
Daiichi Sankyo announced results from ENTRUST-AF PCI, a trial of its Lixiana (edoxaban) plus a P2Y12 inhibitor compared to vitamin K agonist (VKA) plus P2Y12 inhibitor and acetyl salicylic acid (ASA), or aspirin. The trial was conducted in atrial fibrillation (AF) patients after successful percutaneous coronary intervention (PCI).
The composite endpoint was major or clinically-relevant non-major bleeding over 12 months. AF is an irregular and rapid heartbeat. When this occurs, blood pools and thickens in the chambers of the heart. This causes a greater risk of blood clots, which can break off and travel to the brain and potentially trigger a stroke. It is the most common type of heart rhythm disorder.
ENTRUST-AF PCI enrolled 1,506 patients with AF after a successful stent replacement for ACS or stable CAD. They were randomized to receive either once-a-day Lixiana plus a P2Y12 inhibitor for a year or a VKA in combination with a P2Y12 inhibitor and 100 mg of aspirin.
Major or clinically relevant non-major bleeding occurred in 128 patients in the Lixiana group and 152 in the VKA group. Basically, this showed non-inferiority for the Lixiana combination therapy for this patient population. The company indicates there was “a trend toward less bleeding with edoxaban, though, results did not show statistical superiority.”
“For patients with atrial fibrillation receiving PCI, an antithrombotic treatment strategy that prevents both bleeding and potential coronary events is critical,” said Andreas Goette, Chief Physician, St. Vincez-Hospital Paderborn, Germany, Department of Cardiology and Intensive Care Medicine and the study’s principal investigator.
Goette added, “These results from the ENTRUST-AF PCI study support the use of a dual antithrombotic therapy with edoxaban plus a P2Y12 inhibitor as an alternative option with an equivalent safety profile compared to VKA-based triple therapy, including a P2Y12 inhibitor, plus risk adapted ASA for a duration of one to 12 months.”
Brand name P2Y12 inhibitors include Bristol-Myers Squibb’s Plavix (clopidogrel), Daiichi-Sanyko and Eli Lilly’s Effient (prasugrel), AstraZeneca’s Brilinta (ticagrelor) and Chiesi Farmaceutici’s Kengreal (cangrelor).
All bleeding events observed in the study were consistent across all common bleeding definitions. There were four cases of intracranial hemorrhage in patients receiving Lixiana and nine in the VKA-treated cohort. One patient died from bleeding in the Lixiana group and seven died in the VKA cohort.
ENTRUST-AF PCI is one of more than 10 clinical trials that are part of the Edoxaban Clinical Research Programme. All told, more than 100,000 patients globally are expected to participate in these programs.
“These results reinforce the value of the approved regimen of edoxaban for AF treatment in post-PCI patients, providing the potential for less bleeding compared to current standard-of-care VKA-based triple therapies without significant differences in ischemic events,” stated Hans Lanz, vice president, Global Medical Affairs Specialty & Value Products for Daiichi Sankyo. “ENTRUST-AF PCI is part of the Edoxaban Clinical Research Programme, which is designed to address a broad range of cardiovascular conditions and patient types including the elderly. We are encouraged by these results which represent an important advancement in our understanding of how to best manage AF patients post-PCI.”