LB-469807-05 OUTCOMES WITH AND WITHOUT ORAL ANTICOAGULATION IN PATIENTS WITH PRIOR STROKE AND DEVICE-DETECTED ATRIAL FIBRILLATION: THE NOAH-AFNET 6 TRIAL

Introduction: Patients with a prior stroke are at high risk of recurrent strokes. In patients with ECG-documented atrial fibrillation (AF), anticoagulation reduces subsequent strokes. Detection of short and rare episodes of atrial fibrillation using implanted devices (device-detected AF, DDAF) is common in patients with a prior stroke and these patients are often treated
with an anticoagulant when DDAF is detected. Data on the effectiveness and safety of oral anticoagulation in patients a prior stroke and DDAF but no ECG-documented AF are lacking.

Methods: This prespecified secondary analysis of NOAH-AFNET 6 with post-hoc elements assessed the effects of oral anticoagulation on stroke, systemic embolism and
cardiovascular death (primary outcome) and major ISTH bleeding and death (safety outcome) in patients with DDAF and a prior stroke in the randomized, double-blind, double-dummy
NOAH-AFNET 6 trial.

Results: The analysis population consisted of 253/2534 patients with DDAF and a prior stroke or transient ischemic attack at baseline (mean age 78 years, 36.4% women). These patients
were randomized to anticoagulation with edoxaban or no anticoagulation containing aspirin in patients with a prior stroke or TIA. Interaction analysis did not detect a treatment interaction
with prior stroke for any of the primary and secondary time-to- event outcomes. Anticoagulation did not reduce primary outcome events within this subgroup (no anticoagulation: 16/131 patients
with an event (6.3%/patient-year); anticoagulation: 14/122 patients (5.7%/patient-year), and the rate of recurrent stroke was not significantly different between treatment groups
(anticoagulation: 4/122 (1.6%/patient-year); no anticoagulation: 6/131 (2.3%/patient-year)). Anticoagulation markedly increased major ISTH bleeding in patients with prior stroke compared to
aspirin (adjusted hazard ratio 4.2 [0.9-19.9]; patients without prior stroke: adjusted hazard ratio 1.9 [1.2-3.2]; interaction p-value50.068).

Application: In patients with a prior stroke and device-detected AF without ECG-documented AF, therapeutic decisions need to consider the effects of anticoagulation on stroke, bleeding and
death. Based on this subgroup analysis in 253 patients in NOAH-AFNET 6, that decision will not be easy. We need better methods to estimate stroke risk in patients with device-detected AF.

Next Steps/Future: The findings will help clinicians and call for validation in other data sets, including in the ARTESiA trial and in a patient-level meta analysis of both trials.