The Non-Vitamin K Antagonist Oral Anticoagulants in Heart Disease: Section V-Special Situations.

Non-vitamin K antagonist oral anticoagulants (NOACs) include dabigatran, which inhibits thrombin, and apixaban, betrixaban, edoxaban and rivaroxaban, which inhibit factor Xa. In large clinical trials comparing the NOACs with the vitamin K antagonist (VKA) warfarin, dabigatran, apixaban, rivaroxaban and edoxaban were at least as effective for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism, but were associated with less intracranial bleeding. In addition, the NOACs are more convenient to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. Consequently, the NOACs are now replacing VKAs for these indications, and their use is increasing. Although, as a class, the NOACs have a favourable benefit-risk profile compared with VKAs, choosing among them is complicated because they have not been compared in head-to-head trials. Therefore, selection depends on the results of the individual trials, renal function, the potential for drug-drug interactions and preference for once- or twice-daily dosing. In addition, several 'special situations' were not adequately studied in the dedicated clinical trials. For these situations, knowledge of the unique pharmacological features of the various NOACs and judicious cross-trial comparison can help inform prescription choices. The purpose of this position article is therefore to help clinicians choose the right anticoagulant for the right patient at the right dose by reviewing a variety of special situations not widely studied in clinical trials.
Competing Interests: The authors declare the following potential conflicts of interest: Raffaele De Caterina declares fees, honoraria and research funding from Sanofi-Aventis, Boehringer Ingelheim, Bayer, BMS/Pfizer, Daiichi-Sankyo, Novartis, MSD and Portola. Walter Ageno declares honoraria from Boehringer Ingelheim, Bayer, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Aspen, Stago, CSL Behring and Portola, and research funding from Bayer. Giancarlo Agnelli declares honoraria from Bayer, BMS/Pfizer, Daiichi Sankyo and Sanofi. Noel C. Chan declares honoraria from Bayer and Boehringer Ingelheim. Hans-Christoph Diener declares honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Abbott, Achelios, Allergan, AstraZeneca, Bayer Vital, BMS, Boehringer Ingelheim, CoAxia, Corimmun, Covidien, Daiichi-Sankyo, D-Pharm, Fresenius, GlaxoSmithKline, Janssen-Cilag, Johnson & Johnson, Knoll, Lilly, MSD, Medtronic, MindFrame, Neurobiological Technologies, Novartis, Novo-Nordisk, Paion, Parke-Davis, Pfizer, Portola, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Syngis, Talecris, Thrombogenics, WebMD Global, Wyeth and Yamanouchi. Financial support for research projects was provided by AstraZeneca, GSK, Boehringer Ingelheim, Lundbeck, Novartis, Janssen-Cilag, Sanofi-Aventis, Syngis and Talecris. The Department of Neurology at the University Duisburg-Essen received research grants from the German Research Council (DFG), German Ministry of Education and Research (BMBF), European Union, NIH, Bertelsmann Foundation and Heinz-Nixdorf Foundation. Hans-Christoph Diener has no ownership interest and does not own stocks of any pharmaceutical company. Within the past year he served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerznews, Stroke News, as co-editor of Cephalalgia, and is on the editorial board of Lancet Neurology, Stroke, European Neurology and Cerebrovascular Disorders. He chairs the Treatment Guidelines Committee of the German Society of Neurology and contributed to the EHRA and ESC guidelines for the treatment of AF. Elaine Hylek declares honoraria from Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, DOASENSE, Janssen, Medtronic and Portola, and research funding from Janssen. Gary E. Raskob declares consultant fees and/or honoraria from Bayer, BMS, Boehringer-Ingelheim, Daiichi-Sankyo, Eli-Lilly, Janssen, Johnson & Johnson, Novartis, Pfizer and Portola. Deborah M. Siegal declares honoraria for presentations from Bayer, Portola, BMS-Pfizer and Servier. Freek W.A. Verheugt declares having received educational and research grants from Bayer Healthcare, as well as honoraria for consultancies/presentations from Bayer Healthcare, BMS/Pfizer, Daiichi-Sankyo and Boehringer Ingelheim. Gregory Y. H. Lip is a consultant for Bayer/Janssen, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo; and speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim and Daiichi-Sankyo. No fees are directly received personally. Jeffrey I. Weitz declares consultancy fees and honoraria from Boehringer Ingelheim, Bayer, Janssen, BMS/Pfizer, Daiichi-Sankyo, Novartis, Portola, IONIS and Servier.
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