ESC Congress 2026 Abstract · Oct 26, 2026
Does the efficacy of DOACs in atrial fibrillation differ by heart failure phenotype? a real-world analysis of 315,000 patients
By Beveridge E, Lissard M, Thaker V et al.
Background: Heart failure (HF) and atrial fibrillation (AF) often coexist and are associated with increased risk of thromboembolism and mortality. While direct oral anticoagulants (DOACs) are standard of care for stroke prevention in AF, data comparing their real-world between comorbid heart failure phenotypes remains limited. Purpose: This study aims to evaluate the association of DOAC therapy with stroke and mortality in patients with AF and Heart Failure with Reduced Ejection Fraction (HFrEF) compared to patients with AF and Heart Failure with Preserved Ejection Fraction (HFpEF). Methods: Using the TriNetX research network,154,960 patients with AF and HFrEF receiving DOAC therapy were identified and propensity score matched 1:1 to patients with AF and HFrEF not receiving DOACs. A parallel analysis was conducted in a separate cohort of 161,677 patients with AF and HFpEF. Propensity matching was conducted with demographic information and AHA PREVENT risk factors. Primary outcomes were 5-year all-cause mortality and 5-year stroke/transient ischemic attack (TIA). Risk ratios (RR) with 95% confidence intervals were calculated following propensity matching. Results: Across both heart failure phenotypes, DOAC use was associated with significant reductions in stroke and mortality. In patients with HFrEF, DOAC therapy was associated with both a 8.5% reduction in all-cause mortality (RR 0.915, 95% CI: 0.903-0.927, p<0.001) and a 10.9% relative risk reduction for stroke (RR 0.891, 95% CI: 0.866-0.917, p<0.001). In patients with HFpEF, DOAC therapy was associated with a 7.6% relative risk reduction for stroke (RR 0.924, 95% CI: 0.899-0.949, p<0.001) and a 7.6% reduction in all-cause mortality risk (RR 0.924, 95% CI: 0.912-0.937, p<0.001). While the point estimate for stroke risk reduction was numerically greater in HFrEF than in HFpEF (RR 0.891 vs. 0.924), confidence intervals for relative risk estimates overlapped between cohort analyses. Conclusions: DOAC therapy is associated with significant reductions in stroke and mortality across both heart failure phenotypes. However, the trend toward greater stroke reduction in HFrEF (10.9% vs 7.6%) suggests that the benefit of anticoagulation may be augmented in patients with HFrEF, which may reflect differences in thromboembolic risk profiles between phenotypes. due to higher burden of stasis-related thromboembolism. These findings reinforce the benefit of anticoagulation across HF phenotypes but suggest potential phenotype-specific differences that warrant further study.