Aprocitentan and the endothelin system in resistant hypertension

Area of Science:

• Cardiovascular Pharmacology
• Hypertension Research
• Drug Discovery

Background:

• Endothelin is a potent vasoconstrictor and mediator in hypertension and end-organ damage.
• A significant portion of the hypertensive population exhibits resistance to multiple antihypertensive drugs.
• Endothelin system activation is observed in salt-sensitive hypertension and in populations at risk for resistant hypertension.

Purpose of the Study:

• To discuss the research leading to the discovery of aprocitentan, a dual endothelin receptor antagonist (ERA).
• To explore the rationale for investigating aprocitentan in difficult-to-treat hypertension.
• To highlight the potential of targeting the endothelin system for resistant hypertension.

Main Methods:

• Review of preclinical research on the endothelin system's role in hypertension.
• Discussion of the development pathway for aprocitentan as a dual ERA.
• Analysis of clinical trial data (Phase 3) for aprocitentan in resistant hypertension.

Main Results:

• Endothelin's multifaceted role in hypertension pathophysiology is established.
• Aprocitentan demonstrates potent dual endothelin receptor antagonism.
• Phase 3 development targets difficult-to-treat and resistant hypertension cases.

Conclusions:

• The endothelin system is a promising therapeutic target for resistant hypertension.
• Aprocitentan represents a novel therapeutic strategy for patients unresponsive to current treatments.
• Targeting endothelin receptors may overcome resistance mechanisms in severe hypertension.