Safety and effectiveness of rivaroxaban thromboprophylaxis in adrenocorticotropic hormone–dependent Cushing syndrome

CONTEXT: Adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome (CS) is associated with a markedly increased risk of venous thromboembolism (VTE), yet thromboprophylaxis strategies remain inconsistent across clinical practice. In 2019, our center introduced routine oral rivaroxaban prophylaxis (10 mg once daily) for all patients with ACTH-dependent CS. OBJECTIVE: To evaluate the safety and effectiveness of routine rivaroxaban prophylaxis in ACTH-dependent CS. METHODS: We retrospectively reviewed 70 adults with ACTH-dependent CS managed between 2012 and 2025 (29 pre-2019 and 41 post-2019) to compare VTE incidence before and after the introduction of rivaroxaban. RESULTS: There were no differences in baseline characteristics between the 2 groups. Cushing disease (ie, secondary to a pituitary corticotroph adenoma) was the most common subtype (26/29 pre-2019 and 34/41 post-2019). Among patients without routine prophylaxis (pre-2019), 4 patients (13.8%) developed 6 VTE events, occurring both pre- and postoperatively. In the post-2019 cohort, 5 patients experienced 7 VTE events before endocrine assessment and before rivaroxaban could be initiated. Two had recurrent VTE and were already receiving long-term treatment-dose anticoagulation; therefore, 39 of the 41 proceeded with rivaroxaban prophylaxis. No major or minor bleeding complications were observed. Hematological parameters remained stable, and all patients completed the prescribed prophylaxis course (median duration: 7.9 months). CONCLUSION: In our cohort, VTE incidence was 13.8% without prophylaxis and did not occur after the introduction of routine rivaroxaban. Prophylactic oral rivaroxaban in ACTH-dependent CS was safe and effective in preventing new, recurrent, perioperative, and postoperative VTE events, supporting its early initiation at diagnosis and continuation through the peri- and postoperative period.