Mechanism and pharmacological analysis of aprocitentan in the treatment of pulmonary arterial hypertension

Aprocitentan (aprocitentan) is a new type of endothelin receptor antagonist, mainly used to treat pulmonary arterial hypertension (PAH). Pulmonary hypertension is a serious cardiovascular disease characterized by elevated pulmonary artery pressure, often accompanied by increased right heart load and decreased heart function. If not effectively controlled, it may develop into right heart failure. The core mechanism of aprecitentan is to inhibit the activity of endothelin -1 (ET-1) receptor, thereby regulating vascular tone and improving hemodynamic indicators, providing new treatment options for PAH patients.

From a pharmacological perspective, aprecitentan is an orally effective, non-selective ET receptor antagonist that can act on both ETA and ETB receptors. ETA receptors are mainly distributed on vascular smooth muscle cells, and their activation will lead to vasoconstriction and cell proliferation, while ETB receptors are expressed in vascular endothelial cells and achieve vasodilation by promoting the release of nitric oxide and prostacyclin. Aprecitentan antagonizes the contractile effect of ETA receptors and partially blocks ETB receptors, reducing vascular smooth muscle proliferation and improving vascular remodeling of pulmonary arteries, thereby reducing pulmonary artery pressure and improving right heart load.

Clinical studies have shown that aprecitentan has significant efficacy in improving exercise tolerance, hemodynamics and clinical symptoms in patients with pulmonary hypertension. During short-term treatment, patients receiving aprecitentan experienced significant decreases in systolic pulmonary artery pressure and mean pulmonary artery pressure, while cardiac output increased and cardiac index improved. This improvement in hemodynamics can reduce the load on the right heart, delay disease progression, and improve patients' quality of life. In addition, aprecitentan also showed positive effects in improving heart function indicators such as 6 minute walking distance, NYHA classification, and NT-proBNP, proving that it can substantially improve clinical symptoms.

The pharmacological properties of aprecitentan are also reflected in its high oral bioavailability and long half-life, which allows it to maintain stable blood concentration with once-daily administration. This method of administration facilitates long-term treatment and patient compliance management. At the same time, drug metabolism mainly relies on liver enzymes. Patients with impaired renal function need to adjust the dosage according to the guidance of a doctor. Adverse drug reactions are relatively controllable. The most common ones are mild to moderate edema, headache or nasal congestion, and most of them are reversible and can be alleviated by adjusting the dosage or combining with symptomatic treatment. and otherETCompared with receptor antagonists, aprecitentan is well tolerated and has less impact on blood pressure. It shows safety advantages when used as a monotherapy or in combination with other targeted drugs.

Taken together, aprecitentan reduces vasoconstriction and inhibits vascular smooth muscle proliferation through dual ET receptor antagonism mechanisms, fundamentally improving the hemodynamic status of pulmonary hypertension. Its clinical application can not only improve patients' exercise tolerance and quality of life, but may also delay the deterioration of right ventricular function and disease progression. In the future, with the accumulation of more long-term follow-up and multi-center research data, the role of aprecitentan in the treatment of pulmonary arterial hypertension is expected to be further clarified, and a safer and more efficient long-term management solution will be provided for patients. At the same time, its convenience of oral administration and good tolerability make it highly valuable for clinical promotion in individualized treatment of PAH.

Reference materials:https://en.wikipedia.org/wiki/Aprocitentan