Aprocitentan: A novel endothelin receptor antagonist in the treatment of resistant hypertension
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Abstract
The previous mechanism of action of antihypertensive drugs works by blocking of salt and water reabsorption including renin-angiotensin system (RAS) blockers and diuretics, or directly vasodilating blood vessels including calcium channel blockers and beta-adrenoceptor blockers. The endothelin (ET) system has emerged as a new pathway resulting in a potent vasoconstriction which is related to the pathogenesis of hypertension. Aprocitentan, a novel endothelin receptor antagonist, lowering blood pressure by inhibition of ET-1 from binding to both ETA/ETB receptors to produce vasodilation. Its effects lead to reducing cell hypertrophy and hyperproliferation, inflammation, and fibrosis, and thereby slowing organ damages and any cardiovascular complications. It is now approved by the US Food and Drug Administration in March, 2024 for the indication of resistant hypertension in combination with other antihypertensive agents. The highlight keys of aprocitentan include less drug-drug interactions since its metabolism is independent of cytochrome 450 and no dose adjustment is required in patients with mild to moderate of liver or renal impairments. In addition, aprocitentan allows for once-daily dosing, due to its long acting, is thus convenient for administration and promotes medication adherence. The most common side effects are fluid retention and hemodilution, resulting in anemia. Furthermore, long-term adverse drug events monitoring should be performed.
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