Thromboembolism and bleeding in patients with atrial fibrillation and stage 4 chronic kidney disease: impact of biomarkers

Background: Chronic kidney disease (CKD) is considered a risk factor for thromboembolic and bleeding events in patients with atrial fibrillation (AF). Aims: We sought to assess predictors of clinical outcomes among AF patients with advanced CKD. Methods: In a prospective cohort study, we enrolled 180 AF patients with stage 4 CKD, defined as estimated glomerular filtration rate of 15–29 ml/min/1.73 m2, on vitamin K antagonists (n = 90), and non-vitamin K antagonists oral anticoagulants (n = 90). We assessed biomarkers, including growth differentiation factor-15, cystatin C, and high-sensitivity cardiac troponin T, and prothrombotic state parameters, including plasma fibrin clot permeability (Ks). Results: The median age of the patients was 71.0 (64.0–75.0) years (men 65.0%). The median estimated glomerular filtration rate was 24.0 (21.0–25.0) ml/min/1.73 m2 while the median CHA2DS2-VASc score was 3.0 (2.0–4.0). Age (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.02–1.20) and decreased Ks (HR, 0.55; 95% CI, 0.34–0.90) were associated with thromboembolic events (n = 18; 4.7% per year). Previous bleeding (HR, 3.21; 95% CI, 1.22–8.45), growth differentiation factor-15 (HR, 1.48; 95% CI, 1.29–1.69), cystatin C (HR, 9.24; 95% CI, 2.15–39.67), and high-sensitivity cardiac troponin T (HR, 1.30; 95% CI, 1.14–1.48) were independent predictors of major or clinically relevant non-major bleeding (n = 27; 7.1% per year). After adjustment for age and comorbidities, only cystatin C (HR, 3.95; 95% CI, 1.08–14.37) predicted mortality (n = 25; 6.5% per year). Conclusions: Novel biomarkers might be useful in risk stratification of thromboembolic and bleeding events in AF patients with stage 4 CKD receiving oral anticoagulants.