Endothelin Receptor Antagonists for the Treatment of Hypertension: Recent Data from Clinical Trials and Implementation Approach

Purpose of Review:
The endothelin system plays a key role in the pathophysiology of hypertension and remains inadequately addressed by current therapeutic strategies. This review explores the potential of dual endothelin receptor antagonists as a treatment for resistant hypertension.
Recent Findings:
The PRECISION trial recently demonstrated that the dual endothelin receptor antagonist aprocitentan significantly lowers blood pressure in patients with resistant hypertension. Notably, aprocitentan was particularly effective in older adults (≥75 years), African-American patients, and those with diabetes or advanced chronic kidney disease. In addition to blood pressure reduction, aprocitentan also decreased proteinuria. The drug was generally well tolerated, with fluid retention manageable through careful monitoring and diuretic dose adjustment. These findings position aprocitentan as a promising new option for managing resistant hypertension, especially in patient populations that are traditionally difficult to treat.