Non-vitamin-K oral anticoagulants (NOACs) for the prevention of secondary stroke

ABSTRACT

Introduction: In patients with atrial fibrillation (AF), oral anticoagulation with vitamin K antagonists (VKA) (warfarin, phenprocoumon) is effective both for primary and secondary stroke prevention with a 60–70% relative reduction in stroke risk compared with placebo. Mortality is reduced by 26%. VKA have a number of well-documented shortcomings which were overcome by non-vitamin-K oral anticoagulants (NOACs).

Areas covered: Results of randomized trials for four NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) have been published (ARISTOTLE, RE-LY, ENGAGE, ROCKET-AF). In this review, the authors discuss the results in subgroups of patients with prior transient ischemic attacks or ischemic stroke. In aggregate, the NOACs are superior to warfarin for secondary prevention and result in a 50% reduction in intracerebral hemorrhage. Apixaban was superior to aspirin in the AVERROES trial and had a similar rate of major bleeding complications.

Expert opinion: NOACs add to the therapeutic options for secondary stroke prevention in patients with AF and offer advantages over warfarin including a favorable bleeding profile and convenience of use. Aspirin should no longer be used for secondary stroke prevention in patients with AF.

KEYWORDS:

• Atrial fibrillation
• TIA
• stroke
• secondary stroke prevention
• warfarin
• aspirin
• apixaban
• dabigatran
• edoxaban
• rivaroxaban

Article highlights

• Four new anticoagulants (NOACs) have been approved by the US FDA and the European Medicines Agency for indications including stroke prevention in AF.

• Meta-analysis comparing the efficacy of the four NOACs versus warfarin for prevention of secondary stroke demonstrated superiority of the NOACs.

• These four NOACS also caused fewer intracranial hemorrhages than warfarin.

• The NOACs are more convenient to use because they do not require anticoagulation monitoring, are not affected by food, and have fewer concomitant drug interactions.

• All guidelines recommend NOACs for secondary stroke prevention. No single NOAC is preferred over another.

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Declaration of interest

HC Diener received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Abbott, Achelios, Allergan, AstraZeneca, Bayer Vital, Bristol-Myers Squibb, Boehringer Ingelheim, CoAxia, Corimmun, Covidien, Daiichi-Sankyo, D-Pharm, Fresenius, GlaxoSmithKline, Janssen-Cilag, Johnson & Johnson, Knoll, Eli Lilly and Company, Merck Sharp and Dohme, Medtronic, MindFrame, Neurobiological Technologies, Novartis, Novo Nordisk, Paion, Parke-Davis, Pfizer, Portola, Sanofi, Schering-Plough, Servier, Solvay, St. Jude, Syngis, Talecris, Thrombogenics, WebMD Global, Wyeth and Yamanouchi. Financial support for research projects was provided by AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Lundbeck, Novartis, Janssen-Cilag, Sanofi, 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. HC Deiner also declares that he has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerznews, Stroke News, as co-editor of Cephalalgia and on the editorial board of Lancet Neurology, Stroke, European Neurology and Cerebrovascular Disorders. HC Deiner chairs the Treatment Guidelines Committee of the German Society of Neurology and contributed to the EHRA and ESC guidelines for the treatment of AF. G Ntaios received through his institution honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from Sanofi, Boehringer Ingelheim, Galenica, Elpen, Bristol-Myers Squibb/Pfizer, Amgen, and Bayer. H Ntaios also received research support from Bristol-Myers Squibb/Pfizer. M O’Donnell is a steering committee member of AVERROES trial, COMPASS trial and NAVIGATE-ESUS trial. Furthermore, D Easton received research grant support from AstraZeneca for the planning and conduct of the SOCRATES trial (NCT01994720) and from NIH/NINDS as Co-PI on the POINT trial (U01 NS062835–01A1); POINT received free study drug and placebo from Sanofi (NCT00991029). He is a consultant to Boehringer Ingelheim for the planning and conduct of the RE-SPECT ESUS trial (NCT02239120). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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