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

Q: What is the clinical evidence from this study?

Study design: Systematic Review. Population: Atrial fibrillation (AF). Intervention: Mortality risk factors and therapeutic interventions (e.g., DOACs, ablation) vs. Reference groups (e.g., warfarin, medical therapy, or absence of risk factor). Primary outcome: All-cause mortality and cardiovascular mortality.

Q: What does this research mean for the field?

In patients with atrial fibrillation, mortality risk is reduced by NOAC/DOAC therapy, surgical interventions, statins, SGLT2 inhibitors, and early rhythm control, but increased by non-paroxysmal AF, warfarin compared to NOACs, specific antiarrhythmics such as sotalol, and comorbidities. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Jin Luo; Yunpu Niu; Ming Ni; Jingyu Zhang; Zhifu Guo

doi:10.3389/fcvm.2026.1877770

October 13, 2026Frontiers in Cardiovascular MedicineOpen Access

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

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Key result

This umbrella review identified 86 significant mortality risk factors in AF, highlighting that NOACs, catheter ablation, and statins reduce mortality, while warfarin, certain antiarrhythmics, and comorbidities increase risk.

Why the study?

The quality, bias, and strength of evidence regarding mortality risk factors in patients with atrial fibrillation were not comprehensively synthesized.

Do specific demographic, clinical, and therapeutic factors affect mortality in patients with atrial fibrillation?

Key Points

To synthesize published systematic reviews and meta-analyses assessing the methodological quality, bias, and certainty of evidence regarding mortality-related risk factors in patients with atrial fibrillation.
Searched Web of Science, Embase, PubMed, and Cochrane database through May 2025 according to PRISMA guidelines (PROSPERO CRD42024533372).
Screened 5,736 articles and included 182 meta-analyses evaluating 216 distinct risk factors for mortality in atrial fibrillation.
Assessed study methodological quality using the AMSTAR tool and graded the certainty of evidence with the GRADE framework.
Identified 86 factors significantly associated with mortality (32 harmful, 54 protective), supported by 11 high-quality and 9 to 30 moderate-quality evidence factors.
Demonstrated high-quality evidence linking DOAC/NOAC use with lower all-cause mortality compared with warfarin, including in patients with BMI 25–30 kg/m² (HR: 0.84, 95% CI: 0.76–0.92) and TTR below 65% (RR: 0.85, 95% CI: 0.76–0.93), as well as NOACs vs. controls across 12 RCTs (OR: 0.89, 95% CI: 0.84–0.95).
Found increased mortality associated with sotalol (RR: 2.23, 95% CI: 1.03–4.81), digoxin, dronedarone, non-paroxysmal AF, low BMI, and comorbidities (e.g., cancer OR: 2.17; COPD OR: 2.22), whereas catheter ablation, SGLT2 inhibitors, statins, and higher BMI were associated with reduced risk.

Study Design

Type

Systematic Review

Structured PICO

Do specific demographic, clinical, and therapeutic factors affect mortality in patients with atrial fibrillation?

P

Population

An umbrella review of 182 meta-analyses evaluating 216 clinical, demographic, and therapeutic risk factors for mortality in patients with atrial fibrillation.

E

Exposure

Various therapeutic strategies and characteristics, including DOAC/NOAC use, catheter ablation, left atrial appendage closure/occlusion (LAAC/LAAO), SGLT2 inhibitors, statins, and early rhythm control.

C

Comparator

Respective comparators including warfarin/vitamin K antagonists, placebo, rate control, no therapy, and medical antiarrhythmic therapy.

O

Outcome

All-cause mortality.hard clinical

This umbrella review comprehensively maps mortality predictors in atrial fibrillation, reinforcing guideline recommendations that NOACs, ablation, and aggressive comorbidity management significantly improve patient survival.

Limitations

Many associations are based on low-to-very-low certainty evidence
Residual confounding likely in original observational data
Significant heterogeneity due to differences in study settings, populations, and designs
Evidence of publication bias detected in some risk factors
Significant heterogeneity observed in 40.3% of the analyzed risk factors.
Most risk factor associations were supported by low- or very-low-certainty evidence.
Evidence of publication bias detected for 11 risk factors, including ablation versus drug therapy.

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Favors NOACs, ablation, and statins to reduce AF mortality; confirms and extends prior meta-analyses with high-quality GRADE evidence.

Abstract

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

Discussion

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Cite This Study

Luo et al. (2026) conducted a systematic review in Atrial fibrillation (AF). Mortality risk factors and therapeutic interventions (e.g., DOACs, ablation) vs. Reference groups (e.g., warfarin, medical therapy, or absence of risk factor) was evaluated on All-cause mortality and cardiovascular mortality. This umbrella review identified 86 significant mortality risk factors in AF, highlighting that NOACs, catheter ablation, and statins reduce mortality, while warfarin, certain antiarrhythmics, and comorbidities increase risk.

synapsesocial.com/papers/6ad2187bfc66cec880534e0a https://doi.org/10.3389/fcvm.2026.1877770

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

Key Points

Study Design

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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

Key Points

Study Design

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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