Factors associated with mortality in patients with atrial fibrillation: an umbrella review of systematic reviews and meta-analyses.

BACKGROUND: This study synthesized published meta-analyses to assess the quality, bias, and strength of evidence regarding mortality risk factors in patients with atrial fibrillation (AF). METHODS: Web of Science, Embase, PubMed, and Cochrane database were used to search the literature up to May 2025. Eligible studies were systematic reviews or meta-analyses investigating AF-related mortality risk factors. AMSTAR tool was used to assess methodological quality and GRADE was used to evaluate evidence certainty. RESULTS: A total of 216 risk factors were identified. Among them, 86 showed significant associations with mortality, while 130 did not. Based on GRADE ratings, 11 were high-quality significant factors, and 9 were of moderate-quality. Factors linked to increased mortality included certain medications (digoxin, dronedarone, sotalol; warfarin/VKA vs. NOAC was associated with higher mortality), comorbidities (cancer, COPD, diabetes, anemia, frailty, LVH, peripheral artery disease), demographic characteristics (older age, smoking, BMI <18.5, Latin American ethnicity), and AF subtype (persistent or non-paroxysmal). In contrast, reduced mortality was associated with NOAC or DOAC use, higher BMI (25-30 or ≥30), surgical interventions (catheter ablation, LAAC/LAAO), other medications (SGLT2 inhibitors, statins), and early rhythm control. CONCLUSION: This review highlights key factors associated with mortality in AF. Increased risk was observed with warfarin/VKA use (vs. NOAC), certain antiarrhythmic drugs, comorbidities, low BMI, older age, smoking, and non-paroxysmal AF. In contrast, NOAC use, surgical interventions, high BMI, statin and SGLT2 inhibitor therapy, and early rhythm-control strategies were linked to reduced mortality risk.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024533372, PROSPERO CRD42024533372.