title: Comparison of the phase III clinical trial designs of novel oral anticoagulants versus warfarin for the treatment of nonvalvular atrial fibrillation: implications for clinical practice.
abstract: Although vitamin K antagonists (VKAs) have been the backbone of thromboprophylaxis in nonvalvular atrial fibrillation, their limitations have encouraged the development of a new generation of oral anticoagulants. This review compares the different designs and procedures used to conduct four phase III trials that tested dabigatran, rivaroxaban, apixaban, and edoxaban versus VKAs. Although pharmacologic characteristics and results of the main trials are briefly discussed, this review mainly focuses on study designs, enrollment criteria, populations studied, quality metrics, and transition strategies between oral anticoagulants. While each of the trials was of high quality, performed independently, and led by independent academic groups, substantial differences exist in terms of drug pharmacology and trial characteristics. Caution is advised when comparing results across trials as practicing clinicians strive to personalize anticoagulation treatments for their individual patients. We believe that the differences in the pharmacokinetic and pharmacodynamic profiles of the available novel oral anticoagulants (NOACs), coupled with substantial heterogeneity in the trial populations and designs and procedures used to conduct the trials, support an important role for each of the NOACs dependent upon the specific clinical scenario faced by the practicing clinician.
authors: Department of Medicine, Brigham and Women's Hospital, 75 Francis St., Phyllis Jen Center for Primary Care (Suite A), Boston, MA, 02115, USA.
authors: Carlos J
authors: CJ
authors: Gonzalez-Quesada
authors: Robert P
authors: RP
authors: Giugliano
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001562:Benzimidazoles / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D000069604:Dabigatran; D006801:Humans; D009025:Morpholines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D012107:Research Design; D000069552:Rivaroxaban; D013844:Thiazoles / Q000627:therapeutic use; D013876:Thiophenes / Q000627:therapeutic use; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D009025:Morpholines; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; D013876:Thiophenes; D015091:beta-Alanine; D014812:Vitamin K; C522181:apixaban; D014859:Warfarin; D000069552:Rivaroxaban; D000069604:Dabigatran; C552171:edoxaban