Aprocitentan, an endothelin receptor antagonist for resistant hypertension

ABSTRACT Resistant hypertension (RH) is defined as blood pressure (BP) that remains uncontrolled with use of three or more antihypertensive medications or BP that is controlled with use of four antihypertensive medications. Aprocitentan is a newly approved drug for RH, offering a mechanism unique from currently available antihypertensive drugs. It serves to block endothelin-A and endothelin-B to reduce vasoconstriction. The drug, which is taken once daily, has been shown to yield sustainable reductions in BP across various settings, and it may be especially beneficial for those with chronic kidney disease. Risks with use include fluid retention, anemia, mild hepatic enzyme elevations, and—though less common than with other endothelin antagonists—hepatotoxicity. Aprocitentan is contraindicated in pregnancy, as it includes a boxed warning for embryo-fetal toxicity. Although this new drug expands available options for RH, it requires careful patient selection and monitoring. Finally, cost and insurance coverage may limit access.