Phenotypic clustering and ABC pathway adherence in patients with atrial fibrillation at high risk of bleeding and stroke: Insights from three global registries.

Background

Patients with atrial fibrillation (AF) who are at increased risk of both thrombotic and haemorrhagic events represent a heterogeneous and broad clinical entity, characterized by the presence of several Janus-faced risk factors. We aimed to identify clinical phenotypes and assess the association of ABC pathway adherence with one-year outcomes in patients with AF at high risk of both stroke and bleeding.

Methods

AF patients who had HAS-BLED score ≥3 and CHA2DS2-VASc score ≥2 were included. Hierarchical clustering was applied to identify phenotypic subgroups. We assessed the impact on net adverse clinical event (NACE) of adherence to the integrated care based on the Atrial fibrillation Better Care (ABC) pathway.

Results

A total of 2,535 patients (mean age 75.4 ± 7.8 years; 58.3% male) were enrolled. Cluster I had the highest rates of prior thromboembolic and haemorrhagic events with the lowest comorbidity burden; Cluster II comprised the oldest patients with the highest prevalence of dyslipidaemia, heart failure, and peripheral artery disease; Cluster III was the youngest with the highest BMI and alcohol use. Cluster II (aOR 1.93, 95% CI 1.37-2.78), and Cluster III (aOR 1.65, 95% CI 1.10-2.50) were associated with a higher risk of all-cause death compared to Cluster I. Among patients with available ABC pathway data, adherence was associated with lower odds of 1-year MACE (OR 0.39, 95% CI 0.15-0.82).

Conclusion

Three distinct phenotypic clusters were identified, each with heterogeneous clinical characteristics and outcomes, underscoring the need for more individualised, phenotype-informed management strategies in this complex patient population.