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Abstract

Resistant hypertension (RH) is defined as uncontrolled blood pressure (BP) despite the use of three or more antihypertensive agents of different pharmacological classes. The treatment of resistant hypertension remains a challenge, as it is associated with a heightened risk of cardiovascular events. Many preclinical studies have demonstrated the importance of the endothelin pathway in resistant hypertension; however, the therapeutic application of endothelin antagonists in clinical practice has been limited due to various factors. Recently, in March 2024, the FDA approved aprocitentan, an orally active endothelin-1 (ET-1) receptor antagonist that inhibits the binding of ET-1 to ETA and ETB receptors. This is the first medication with a novel mechanism for the treatment of resistant hypertension. This review aims to summarise the available evidence on the discovery, chemical nature, pharmacokinetics, pharmacodynamics, efficacy, and safety of the novel drug aprocitentan in the pharmacotherapy of resistant hypertension. The landmark PRECISION trial demonstrated a significant BP-lowering effect with the use of the dual endothelin receptor antagonist aprocitentan in the treatment of resistant hypertension. Aprocitentan was shown to be particularly effective in patients over 75 years of age, those with a higher cardiovascular-risk profile, patients with diabetes, and individuals with advanced chronic kidney disease (CKD). As a dual receptor antagonist, aprocitentan demonstrated a lower risk of fluid retention and vascular leakage, adverse effects previously observed with other endothelin receptor antagonists. Its mechanism of action, improved efficacy, and excellent tolerability make aprocitentan a promising therapeutic option for resistant hypertension. It may be particularly effective in the treatment of patients with comorbidities, such as diabetes and CKD.

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2026-01-02
2026-02-23

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/content/journals/chyr/10.2174/0115734021433257251128044458
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A New Drug for Resistant Hypertension: Aprocitentan
Bentham Science Publishers ; https://doi.org/10.2174/0115734021433257251128044458
/content/journals/chyr/10.2174/0115734021433257251128044458
/content/journals/chyr/10.2174/0115734021433257251128044458
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  • Article Type:     Review Article
Keywords: dual endothelin-1 receptor antagonist ; oral endothelin receptor antagonist ; Novel anti-hypertensive drug ; resistant hypertension ; aprocitentan ; antihypertensive agents ; precision trial

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