Patterns of comorbidities in atrial fibrillation patients with high thromboembolic risks: a latent class analysis of two prospective registries from the Asia-Pacific and Europe

Abstract Background Oral anticoagulation (OAC) is the cornerstone of management for reducing thromboembolic risk in patients with atrial fibrillation (AF). Whether the OAC treatment was affected by patient’s profile of comorbidities remains unclear. Purposes We aimed to explore potential phenotypes of AF patients with high thromboembolic risks according to comorbidities. Methods We performed an exploratory latent class analysis based on two prospective registries enrolling AF patients from the Asian-Pacific Heart Rhythm Society (APHRS) and EURObservational Research Programme (EORP) using the poLCA package in R. Logistic regression was used to explore the association between latent classes and OAC prescription. Cox models were constructed to examine the effects of OAC across different latent classes on composite outcomes composed of all-cause death and major adverse cardiovascular events. Age and sex were adjusted for all models. Results A total of 9163 AF patients (median age 73.0, Interquartile ranges IQR67.0-79.0 years, 44.9% females) with CHA2DS2-VASc score ≥2 were included. Based on 12 baseline comorbidities, we identified 4 phenotypes (Figure 1): 1) High complexity (11.4% of patients), the oldest (median age 75.0, IQR 67.0-80.0 years), predominantly males (63.4%) with higher prevalence of multiple cardiovascular and non-cardiovascular comorbidities, including hypertension (HTN), coronary artery disease (CAD), heart failure(HF), diabetes, dyslipidaemia, chronic kidney disease (CKD), chronic obstructive pulmonary diseases (COPD); 2) HF group (10.8%), characterised by the highest prevalence of HF; 3) Cardiometabolic (34.0%), composed of younger patients (median age 72.0, IQR 66.0-78.0 years) with highest prevalence of dyslipidaemia and high prevalence of diabetes and cardiovascular disease including HTN and CAD; 4) unspecified type (43.8%), with a relatively low prevalence of comorbidities except HTN. OAC prescription was less common in the high complexity phenotype (odds ratio 0.52, 95% confidence intervalCI 0.43-0.63), compared to the unspecified phenotype (Figure 2A). During a median follow-up of 704 days, OAC treatment was associated with reduced risks of composite outcomes in the overall population (hazard ratio HR 0.51, 95%CI 0.44-0.60), while the benefit was more prominent in the high complexity group (HR 0.44, 95%CI 0.34-0.58, p for interaction0.001) (Figure 2B). Conclusion AF patients with high thromboembolic risks exhibit heterogeneity in burden of comorbidities. Those with complex clinical profile are less likely to receive OAC treatment despite its proven benefits on clinical prognosis. Personalized management strategies are required in the high-risk population.