Atrial fibrillation progression in patients with device-detected subclinical atrial fibrillation: Insights from the ARTESiA trial

BACKGROUND: The Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Subclinical Atrial Fibrillation (ARTESiA) trial enrolled patients with subclinical atrial fibrillation (SCAF) lasting < 24 hours. OBJECTIVE AND METHODS: We assessed the association of SCAF progression to clinical atrial fibrillation or SCAF > 24 hours with adverse outcomes and predictors of SCAF progression. RESULTS: During follow-up (4.1 ± 1.7 years), SCAF progressed in 1250 of 4012 patients (31.2%) at a rate of 9.3% per patient-year. SCAF progression was associated with adverse outcomes, with the following hazard ratios (HRs) and 95% confidence intervals (CIs): all-cause death, 2.12 (1.83-2.45); heart failure death, 4.81 (3.19-7.27); and arrhythmic death, 2.62 (1.58-4.35). The rate of stroke/systemic embolism in patients who remained on blinded aspirin therapy after SCAF progression was 1.42% per patient-year. If one limits the definition of progression to SCAF lasting > 24 hours, the rate was 1.75% per patient-year. Baseline variables modestly predicted SCAF progression (C statistic 0.59; 95% CI 0.57-0.61), including age (HR 1.02 per year; 95% CI 1.01-1.03 per year), male sex (HR 1.30; ; 95% CI 1.14-1.47), heart failure (HR 1.28; 95% CI 1.13-1.46), diabetes mellitus (HR 1.18; 95% CI 1.04-1.34), left atrial diameter > 4.1 cm (HR 1.28; 95% CI 1.08-1.52), and longest baseline SCAF episode duration > 1 hour (HR 1.59; 95% CI 1.42-1.79). CONCLUSION: SCAF progression occurred in >9% of patients per year and was associated with a doubling of the risk of all-cause mortality, driven by increases in both heart failure-related and arrhythmic deaths. Patients who remained on aspirin after SCAF progression had an annual rate of stroke/systemic embolism of 1.42%, which is higher than the threshold currently proposed for oral anticoagulant prophylaxis.