Aprocitentan, a dual endothelin-1 (ET-1) antagonist for treating resistant hypertension: Mechanism of action and therapeutic potential

Hypertension is reaching epidemic proportions worldwide and is a significant public health concern. However, ∼15% of patients with hypertension continue to experience elevated blood pressure, even after taking antihypertensive medications [such as angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), dihydropyridine calcium channel blockers (CCBs) and thiazide diuretics], a condition referred to as resistant hypertension (RH). Within the complex realm of blood pressure regulation and vascular function, endothelin-1 (ET-1), a potent vasoconstrictor, plays a pivotal role. Recent research, particularly a Phase III clinical trial (NCT03541174), has shed light on the potential of aprocitentan, a dual ET-1 receptor antagonist, in significantly lowering blood pressure in individuals with RH. In this review, we summarize the mechanism of action and therapeutic potential of aprocitentan as an innovative approach for treating RH.