Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: Design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation–Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF–TIMI 48)

Background Vitamin K antagonists have been the standard oral antithrombotic used for more than a half century for prevention and treatment of thromboembolism. Their limitations include multiple food and drug interactions and need for frequent monitoring and dose adjustments. Edoxaban is a selective...

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Bibliographic Details
Published in:The American heart journal 2010-10, Vol.160 (4), p.635-641.e2
Main Authors: Ruff, Christian T., MD, Giugliano, Robert P., MD, SM, Antman, Elliott M., MD, Crugnale, Sharon E., MS, Bocanegra, Tomas, MD, Mercuri, Michele, MD, PhD, Hanyok, James, PharmD, Patel, Indravadan, MD, Shi, Minggao, PhD, Salazar, Dan, PhD, McCabe, Carolyn H., BS, Braunwald, Eugene, MD
Format: Article
Language:English
Subjects:
Administration, Oral
Aged
Anticoagulants
Anticoagulants - administration & dosage
Anticoagulants - therapeutic use
Atrial Fibrillation - complications
Atrial Fibrillation - drug therapy
Atrial Fibrillation - physiopathology
Biological and medical sciences
Cardiac arrhythmia
Cardiac dysrhythmias
Cardiology. Vascular system
Cardiovascular
Coronary heart disease
Dose-Response Relationship, Drug
Double-Blind Method
Drug dosages
Drug therapy
Electrocardiography
Factor Xa Inhibitors
Female
Follow-Up Studies
Heart
Hepatitis
Humans
Male
Medical sciences
Middle Aged
Myocardial Infarction - complications
Myocardial Infarction - drug therapy
Myocardial Infarction - physiopathology
Myocarditis. Cardiomyopathies
Nonsteroidal anti-inflammatory drugs
Pyridines - administration & dosage
Pyridines - therapeutic use
Retrospective Studies
Stroke - etiology
Stroke - prevention & control
Thiazoles - administration & dosage
Thiazoles - therapeutic use
Thrombolytic Therapy - methods
Treatment Outcome
Warfarin - administration & dosage
Warfarin - therapeutic use
Women
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Summary:Background Vitamin K antagonists have been the standard oral antithrombotic used for more than a half century for prevention and treatment of thromboembolism. Their limitations include multiple food and drug interactions and need for frequent monitoring and dose adjustments. Edoxaban is a selective and direct factor Xa inhibitor that may provide effective, safe, and more convenient anticoagulation. Study Design ENGAGE AF–TIMI 48 is a phase 3, randomized, double-blind, double-dummy, multinational, noninferiority design megatrial comparing 2 exposure strategies of edoxaban to warfarin. Approximately 20,500 subjects will be randomized to edoxaban high exposure (60 mg daily, adjusted for drug clearance), edoxaban low exposure (30 mg daily, adjusted for drug clearance), or warfarin titrated to an international normalized ratio of 2.0 to 3.0. The edoxaban strategies provide for dynamic dose reductions in subjects with anticipated increased drug exposure. Blinded treatment is maintained through the use of sham international normalized ratios in patients receiving edoxaban. Eligibility criteria include electrical documentation of atrial fibrillation ≤12 months and a CHADS2 score ≥2. Randomization is stratified by CHADS2 score and anticipated drug exposure. The primary objective is to determine whether edoxaban is noninferior to warfarin for the prevention of stroke and systemic embolism. The primary safety end point is modified International Society on Thrombosis and Haemostasis major bleeding. Recruitment began in November 2008. The expected median follow-up is 24 months. Conclusions ENGAGE AF–TIMI 48 is a phase 3 comparison of the novel oral factor Xa inhibitor edoxaban to warfarin for the prevention of thromboembolism in patients with atrial fibrillation.
ISSN:0002-8703
1097-6744
DOI:10.1016/j.ahj.2010.06.042