Predictive thresholds of peak and trough anti-Xa levels for bleeding risk in rivaroxaban-treated nonvalvular atrial fibrillation

Abstract

Abstract Background While anti-Xa assays are increasingly used to monitor rivaroxaban therapy, evidence supporting specific thresholds for bleeding risk remains limited. Objective To determine predictive thresholds of peak and trough anti-Xa levels for bleeding complications in patients with nonvalvular atrial fibrillation (NVAF) receiving rivaroxaban. Methods In this prospective multicenter cohort study conducted at four tertiary care hospitals in Damascus, Syria, we enrolled 70 NVAF patients receiving rivaroxaban (20 mg/day; 15 mg/day if eGFR < 50 mL/min). Anti-Xa levels were measured at peak (1–3 h post-dose) and trough (pre-dose). Patients were followed for 6 months for bleeding events. Results Twenty-five patients (35.7%) experienced bleeding (8 major, 17 minor). Bleeding patients demonstrated significantly higher anti-Xa levels (peak: 399 ± 78 vs. 206 ± 67 ng/mL, p < 0.0001; trough: 41 ± 14 vs. 20 ± 10 ng/mL, p < 0.0001). ROC analysis identified optimal predictive thresholds of 298 ng/mL for peak levels (AUC = 0.985, sensitivity 89.5%, specificity 93.3%) and 27.5 ng/mL for trough levels (AUC = 0.887, sensitivity 86.4%, specificity 76.3%). Conclusion Anti-Xa levels strongly predict bleeding risk in rivaroxaban-treated NVAF patients. The identified thresholds may guide clinical decision-making regarding dose adjustment, particularly in high-risk patients. However, it is important to acknowledge limitations, including the modest sample size and the exclusion of patients on antiplatelet therapy, which may affect generalizability.

Keywords

• Anti-Xa assays
• Rivaroxaban therapy
• Bleeding
• Nonvalvular atrial fibrillation (NVAF)
• Peak anti-Xa levels
• Trough anti-Xa levels