Probing oral anticoagulation in patients with atrial high rate episodes: Rationale and design of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH-AFNET 6) trial

Paulus Kirchhof, Benjamin F Blank, Melanie Calvert, A John Camm, Gregory Chlouverakis, Hans-Christoph Diener, Andreas Goette, Andrea Huening, Gregory Y H Lip, Emmanuel Simantirakis, Panos Vardas, Paulus Kirchhof, Benjamin F Blank, Melanie Calvert, A John Camm, Gregory Chlouverakis, Hans-Christoph Diener, Andreas Goette, Andrea Huening, Gregory Y H Lip, Emmanuel Simantirakis, Panos Vardas

Abstract

Oral anticoagulation prevents ischemic strokes in patients with atrial fibrillation (AF). Early detection of AF and subsequent initiation of oral anticoagulation help to prevent strokes in AF patients. Implanted cardiac pacemakers and defibrillators allow seamless detection of atrial high rate episodes (AHRE), but the best antithrombotic therapy in patients with AHRE is not known.

Rationale: Stroke risk is higher in pacemaker patients with AHRE than in those without, but the available data also show that stroke risk in patients with AHRE is lower than in patients with AF. Furthermore, only a minority of patients with AHRE will develop AF, many strokes occur without a temporal relation to AHRE, and AHRE can reflect other arrhythmias than AF or artifacts. An adequately powered controlled trial of oral anticoagulation in patients with AHRE is needed.

Design: The Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH-AFNET 6 ) trial tests whether oral anticoagulation with edoxaban is superior to prevent the primary efficacy outcome of stroke or cardiovascular death compared with aspirin or no antithrombotic therapy based on evidence-based indications. The primary safety outcome will be major bleeding. NOAH-AFNET 6 will randomize 3,400 patients with AHRE, but without documented AF, aged ≥65 years with at least 1 other stroke risk factor, to oral anticoagulation therapy (edoxaban) or no anticoagulation. All patients will be followed until the end of this investigator-driven, prospective, parallel-group, randomized, event-driven, double-blind, multicenter phase IIIb trial. Patients will be censored when they develop AF and offered open-label anticoagulation. The sponsor is the Atrial Fibrillation NETwork (AFNET). The trial is supported by the DZHK (German Centre for Cardiovascular Research), the BMBF (German Ministry of Education and Research), and Daiichi Sankyo Europe.

Conclusion: NOAH-AFNET 6 will provide robust information on the effect of oral anticoagulation in patients with atrial high rate episodes detected by implanted devices.

Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure
Figure
Flowchart of NOAH–AFNET 6. In the setting of NOAH–AFNET 6, edoxaban 60 mg od is the NOAC of choice. The dose will be reduced to 30 mg od (in accordance with the label for AF) in patients with one of the following characteristics: (1) impaired renal function (creatinine clearance 15-50 mL/min); (2) low body weight (≤60 kg); or (3) patients receiving the glycoprotein P inhibitors ketoconazole, cyclosporine, erythromycin, or dronedarone. In a double-blind design, established indications in the inclusion criteria for antiplatelet therapy will guide the use of blind aspirin or blind placebo for the patients not receiving anticoagulation. Patients randomized to NOAC will not receive aspirin in addition. All patients will be followed until the end of the trial for events. ECGs will be recorded at baseline and in 6-month intervals during follow-up.

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