Phenotypes and outcomes in non-anticoagulated patients with atrial fibrillation: An unsupervised cluster analysis

Background: Patients with atrial fibrillation are characterized by great clinical heterogeneity and complexity. The usual classifications may not adequately characterize this population. Data-driven cluster analysis reveals different possible patient classifications. Aims: To identify different clusters of patients with atrial fibrillation who share similar clinical phenotypes, and to evaluate the association between identified clusters and clinical outcomes, using cluster analysis. Methods: An agglomerative hierarchical cluster analysis was performed in non-anticoagulated patients from the Loire Valley Atrial Fibrillation cohort. Associations between clusters and a composite outcome comprising stroke/systemic embolism/death and all-cause death, stroke and major bleeding were evaluated using Cox regression analyses. Results: The study included 3434 non-anticoagulated patients with atrial fibrillation (mean age 70.3 ± 17 years; 42.8% female). Three clusters were identified: Cluster 1 was composed of younger patients, with a low prevalence of co-morbidities; Cluster 2 included old patients with permanent atrial fibrillation, cardiac pathologies and a high burden of cardiovascular co-morbidities; Cluster 3 identified old female patients with a high burden of cardiovascular co-morbidities. Compared with Cluster 1, Clusters 2 and 3 were independently associated with an increased risk of the composite outcome (hazard ratio 2.85, 95% confidence interval 1.32–6.16 and hazard ratio 1.52, 95% confidence interval 1.09–2.11, respectively) and all-cause death (hazard ratio 3.54, 95% confidence interval 1.49–8.43 and hazard ratio 1.88, 95% confidence interval 1.26–2.79, respectively). Cluster 3 was independently associated with an increased risk of major bleeding (hazard ratio 1.72, 95% confidence interval 1.06–2.78). Conclusion: Cluster analysis identified three statistically driven groups of patients with atrial fibrillation, with distinct phenotype characteristics and associated with different risks for major clinical adverse events.