NOAH-AFNET 6 Studie – TERMINATED following a recommendation from the data safety and monitoring board due to safety concerns and a tendency towards futility.
Study Overview
Brief Summary
NOAH is an investigator-initiated, prospective, parallel-group, double-blind, randomised, multi-centre trial. The objective of the trial is to demonstrate that oral anticoagulation using the NOAC edoxaban is superior to current therapy to pre-vent stroke, systemic embolism, or cardiovascular death in patients with AHRE and at least two stroke risk factors but without AF. The trial will be conducted in several European countries.
Detailed Description
Atrial fibrillation (AF) is a common cause of stroke, especially ischemic stroke. So far, all available data that demonstrate a beneficial effect of oral anticoagulation for stroke prevention have been collected in populations with AF documented by conventional ECG recordings. It is well established that a large proportion of AF episodes remain undiagnosed („silent AF“), and many of these patients present with a stroke as the first clinical sign of AF.
Earlier initiation of anticoagulation could prevent such events. Continuous monitoring of atrial rhythm by implanted devices could close this diagnostic gap. Pacemakers, defibrillators, and cardiac resynchronisation devices already provide automated algorithms alerting to the occurrence of highly organised atrial tachyarrhythmia episodes, also called „subclinical atrial fibrillation“ or, more commonly, „atrial high rate episodes“ (AHRE). Data from large prospectively followed patient cohorts demonstrated that stroke rate is increased in patients with AHRE. A sizeable portion of these patients develops clinically detected AF over time. In these patients, AHRE can be considered as an early manifestation of paroxysmal AF. A few AHRE patients do not develop clinically overt AF, and the absolute stroke rates are lower in patients with AHRE when compared to stroke rates in patients with clinically diagnosed AF.
In light of the bleeding complications associated with oral anticoagulant therapy, there is thus uncertainty about the optimal antithrombotic therapy in patients with AHREs.
The Non-vitamin K antagonist Oral anticoagulants (NOACs) provide similar or slightly better stroke prevention, and appear slightly safer compared to vitamin K antagonists (VKAs). In addition, no individual therapy adjustment of NOACs has to be performed. Edoxaban, a newly introduced NOAC, at a dose regime of 60 mg once daily (OD) has a favourable profile compared to dose-adjusted VKA therapy: In the ENGAGE-TIMI 48 trial, edoxaban prevented strokes at least as effectively as VKA therapy but caused less major bleeding events than VKA therapy
Fazit:
Die Studie wurde offensichtlich abgebrochen, weil die Verhinderung von Schlaganfällen bei AHRE nur sehr moderat war, dafür aber die Blutungskomplikationen deutlich erhöht waren.
Zufällig aufgezeichnetes AHRE (nur durch Schrittmacher erkennbar) scheint von der Antikoagulation nicht zu profitieren.