Hypercoagulopathy, induced by glucocorticoids, is a significant concern in Cushing's Syndrome (CS), increasing the risk of thromboembolic events and cardiovascular issues. A recent analysis has investigated the impact of relacorilant, a selective glucocorticoid receptor modulator (SGRM), and surgical intervention on coagulation markers in CS patients. The findings suggest both treatments can improve hemostatic parameters, potentially reducing the risk of venous thromboembolism (VTE).
The study, which combined data from a phase 2 clinical trial of relacorilant and a retrospective surgical cohort, assessed changes in coagulation markers such as factor VIII, von Willebrand factor, activated partial thromboplastin time (aPTT), and platelet count. The relacorilant study involved patients receiving either a low-dose (100-200 mg/day) or high-dose (250-400 mg/day) of the drug, while the surgical study included patients who underwent surgery for CS at the "Federico II" University of Naples between 2004 and 2021.
Impact on Coagulation Markers
Results indicated that both relacorilant treatment and surgery led to improvements in several coagulation markers. Specifically, factor VIII levels and aPTT showed significant improvement in both groups. These changes suggest a reduction in the hypercoagulable state associated with CS.
"In each study, improvement in several coagulation markers, including factor VIII, in patients with CS during relacorilant treatment and after surgery was observed," the researchers noted.
Relacorilant vs. Surgery
While both treatments showed positive effects, some differences were observed. The relacorilant study showed a reduction in factor VIII without a corresponding reduction in von Willebrand factor, suggesting a potential direct effect of relacorilant on factor VIII synthesis. Additionally, the percentage of patients with abnormal coagulation marker levels was lower in the relacorilant study compared to the surgical study.
Clinical Implications
The findings suggest that relacorilant could be a valuable treatment option for CS patients, especially those at high risk of VTE or who are not suitable candidates for surgery. The study also highlights the potential for relacorilant to mitigate the postoperative rise in coagulation factors that can occur following surgery.
Study Limitations
The authors acknowledge several limitations, including the independent design of the studies, the retrospective nature of the surgical study, the use of concomitant anticoagulants in some relacorilant patients, and the lack of a placebo control group in both studies. The small sample size and the focus on specific coagulation markers also limit the scope of the analysis.
Ongoing Research
Further research is underway to assess relacorilant's impact on coagulation factors in patients with hypercortisolism due to adrenal adenoma or hyperplasia (GRADIENT study, NCT04308590) and in an open-label extension study in patients with CS (NCT03604198). These studies will provide additional insights into the potential benefits of relacorilant in managing CS-related hypercoagulopathy.
