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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

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An Erratum to this article was published on 29 April 2014

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.

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Acknowledgments

We would like to thank Colville Brown, MD, from AlphaBioCom for his technical assistance and formatting of this manuscript. Daiichi Sankyo provided funding for this technical assistance.

Disclosures

RPG is a member of the TIMI Study Group that receives research grant support from Daiichi Sankyo, Johnson & Johnson, and Sanofi. RPG has received honoraria for CME lectures and for consulting, and reimbursement for related travel from Bristol Myers Squibb, Daiichi Sankyo, Janssen, and Sanofi. CJGQ has no potential conflicts of interest that might be relevant to the contents of this review.

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  1. Department of Medicine, Brigham and Women’s Hospital, 75 Francis St., Phyllis Jen Center for Primary Care (Suite A), Boston, MA, 02115, USA

    Carlos J. Gonzalez-Quesada

  2. TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 350 Longwood Ave., 1st Floor Offices, Boston, MA, 02115, USA

    Robert P. Giugliano

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Correspondence to Robert P. Giugliano.

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Gonzalez-Quesada, C.J., Giugliano, R.P. 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. Am J Cardiovasc Drugs 14, 111–127 (2014). https://doi.org/10.1007/s40256-013-0062-z

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