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

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.