Comparative efficacy and safety of direct oral anticoagulants versus warfarin in non-valvular atrial fibrillation patients with adult congenital heart disease. Contemporary real-world propensity-matched retrospective cohort study

Q: What does this research mean for the field?

In patients with adult congenital heart disease and atrial fibrillation, direct oral anticoagulants are associated with lower hazards of adverse net clinical outcomes, bleeding events, and all-cause mortality compared with warfarin, without an increase in embolic risk. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Dennis Kumi; George Blankson; Irene Acheampong; Samuel Odoi; Sudhir Mungee; Timir Baman; Amit Mehrotra; Siddarth Shah

doi:10.1016/j.ijcchd.2026.100691

June 24, 2026International Journal of Cardiology Congenital Heart DiseaseOpen Access

Comparative efficacy and safety of direct oral anticoagulants versus warfarin in non-valvular atrial fibrillation patients with adult congenital heart disease. Contemporary real-world propensity-matched retrospective cohort study

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Why the study?

Adults with congenital heart disease have a rising prevalence of AF and elevated thrombotic and bleeding risks, but the comparative effectiveness of DOACs in this population is not well defined.

Do direct oral anticoagulants (DOACs) improve net clinical outcomes compared to warfarin in adults with congenital heart disease and atrial fibrillation?

Structured PICO

Do direct oral anticoagulants (DOACs) improve net clinical outcomes compared to warfarin in adults with congenital heart disease and atrial fibrillation?

P

Population

27,166 adults with congenital heart disease (ACHD) and atrial fibrillation/flutter (AF) receiving oral anticoagulation. Excluded: mechanical valves, LVAD, antiphospholipid syndrome, or rheumatic mitral stenosis.

I

Intervention

Direct oral anticoagulants (DOACs)

C

Comparator

Warfarin (1:1 propensity-matched)

O

Outcome

Composite embolic events, composite bleeding events, and net clinical outcome (embolism, bleeding, or all-cause mortality)composite

In adults with congenital heart disease and atrial fibrillation, DOACs are associated with improved net clinical outcomes, lower bleeding risk, and reduced mortality compared to warfarin, without increasing embolic risk.

Implication

Comparable thromboembolic and bleeding risks with DOACs versus VKAs in ACHD-AF; observational data leaves open need for RCTs before practice change.

Abstract

Background: Adults with congenital heart disease (ACHD) have a rising prevalence of atrial fibrillation/flutter (AF) and elevated thrombotic and bleeding risk. Although direct oral anticoagulants (DOACs) are established in non-ACHD AF, comparative effectiveness in ACHD is not well defined. Methods: with ACHD and AF receiving oral anticoagulation were identified, excluding those with mechanical valves, LVAD, antiphospholipid syndrome, or rheumatic mitral stenosis. Patients were matched 1:1 to DOAC or warfarin. The primary outcomes were composite embolic events, composite bleeding events, and net clinical outcome (embolism, bleeding, or all-cause mortality). Secondary outcomes included gastrointestinal bleeding, nontraumatic intracranial hemorrhage (ICH), cardioembolic stroke, systemic arterial embolization, cerebral infarction, and all-cause mortality. Associations were estimated using hazard ratios (HRs). Sensitivity analysis was performed to confirm the robustness of magnitude and direction of outcomes. Results: After matching, 27,166 patients were included (13,583 per group). DOAC use was associated with lower hazard of net clinical outcome (HR 0.87, 95% CI 0.81-0.93), driven by reduced composite bleeding (HR 0.82, 95% CI 0.75-0.90) and all-cause mortality (HR 0.68, 95% CI 0.64-0.72). Hazard of composite embolic events did not differ (HR 0.94, 95% CI 0.87-1.03). DOACs were associated with lower hazard of systemic arterial embolization (HR 0.62, 95% CI 0.52-0.73), nontraumatic ICH (HR 0.74, 95% CI 0.61-0.90), and gastrointestinal bleeding (HR 0.84, 95% CI 0.76-0.93). No significant differences were observed for cerebral infarction or cardioembolic stroke. Conclusions: In a large propensity-matched cohort of patients with ACHD and AF, DOAC therapy was associated with lower hazard of net clinical outcome, all bleeding events, and all-cause mortality compared with warfarin, without increased embolic risk.