Blood thinner rivaroxaban prevents clots in ACTH-dependent Cushing’s
Study: Treatment proves effective both before and after surgery
Written by |
The blood-thinning medication rivaroxaban was safe and effective at preventing the formation of blood clots in deep veins or the lungs, known as venous thromboembolism (VTE), in people with adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome, according to a recent study.
The study demonstrated that the treatment prevented both new and recurrent events, including those occurring before and after surgery.
These data provide support that the treatment “should be considered from the time of diagnosis and continued for an extended postoperative period of at least three months in patients with ACTH-dependent [Cushing’s syndrome],” researchers wrote.
The study, “Safety and Effectiveness of Rivaroxaban Thromboprophylaxis in ACTH-dependent Cushing Syndrome,” was published in The Journal of Clinical Endocrinology & Metabolism.
Cushing’s associated with blood clots in deep veins, lungs
Cushing’s syndrome refers to any condition caused by excessive cortisol production, or hypercortisolism. Cushing’s disease, its most common type, is caused by tumors in the brain’s pituitary gland that release abnormally high levels of adrenocorticotropic hormone (ACTH), triggering the adrenal glands, which sit atop the kidneys, to overproduce cortisol. In ectopic Cushing’s, ACTH is released by tumors outside the pituitary gland.
Besides metabolic, cardiovascular, and mental health issues, Cushing’s is also associated with VTE. This includes deep vein thrombosis (DVT), in which blood clots form in deep veins, usually in the legs, and pulmonary embolism, in which clots travel to the lungs.
In this study, researchers at Imperial College London, in the U.K., conducted a retrospective analysis to compare VTE incidence and outcomes before and after the introduction of preventive treatment with rivaroxaban (sold as Xarelto and generics) in patients with ACTH-dependent Cushing’s managed between 2012 and 2025. Rivaroxaban is an anticoagulant, or blood-thinning medication, that prevents the formation of harmful blood clots.
A total of 70 patients were included: 29 treated before 2019 who did not receive routine preventive therapy, and 39 treated after 2019 who received preventive therapy with 10 mg rivaroxaban at diagnosis and continued for three months following surgical removal of the disease-causing tumors.
The mean age of participants was 45.5 years. Most patients were women (approximately 80%) and had Cushing’s disease (83% to 90%), while the remaining patients had ectopic Cushing’s syndrome.
Patients with Cushing’s disease were usually treated surgically
Those with Cushing’s disease were usually treated with transsphenoidal surgery, which removes tumors in the pituitary tumor through a hollow space behind the nose, alone or together with adjuvant medical therapy. Hypercortisolism resolved in 62% of the patients treated with surgery plus medications.
Patients with ectopic Cushing’s were primarily managed surgically (approximately 60%), while about 30% received a combination of surgical and medical therapy. One patient was treated with medical therapy alone.
Before routine prophylaxis, four patients (13.8%) developed six VTE events, prior to and within a month after surgery. One 35-year-old patient had two DVT events in leg veins, before and after surgery, and a 75-year-old had a DVT in veins in both thighs three months after diagnosis and died before surgery.
Our findings align with prior studies demonstrating that proactive [prophylaxis] reduces VTE in [Cushing’s syndrome, and] support consideration of initiating thromboprophylaxis at the time of diagnosis for all patients with ACTH-dependent [Cushing’s].
After 2019, when routine prophylaxis with rivaroxaban was established, five patients had VTE events before Cushing’s diagnosis and treatment initiation. VTE events occurred even in patients with relatively mild hypercortisolism, suggesting “thrombotic events are not confined to those with the highest cortisol levels and that even modest biochemical hypercortisolism may confer clinically relevant risk.”
Among 39 patients who received preventive rivaroxaban, no VTE events or bleeding episodes occurred. All patients completed the prescribed course of rivaroxaban for a mean duration of 7.9 months. Looking at all participants, 13 VTE events occurred in nine patients not treated with rivaroxaban, “suggesting that prophylactic anticoagulation is effective in reducing thrombotic complications in this high-risk population,” the researchers wrote.
“Our findings align with prior studies demonstrating that proactive [prophylaxis] reduces VTE in [Cushing’s syndrome],” and “support consideration of initiating thromboprophylaxis at the time of diagnosis for all patients with ACTH-dependent [Cushing’s],” the researchers added.
