Revolutionizing resistant hypertension: Unlocking the potential of Aprocitentan.

Abstract

Madam,

 Hypertension is a prevalent disease worldwide; however, the therapies for the treatment of hypertension have been unable to meet the desired blood pressure levels in approximately 15% of patients resulting to resistant hypertension. According to the American Heart Association, resistant hypertension is a condition in which the blood pressure remains elevated despite the use of drugs from three different classes of anti-hypertensives. It has been linked with an increasing risk of organ damage and cardiovascular events including ischemic heart failure, stroke.¹

Many novel anti-hypertensive drugs have been have been studied in response to this concern. Aprocitentan, an active metabolite of macitentan is one of them. It acts as a dual ET_A and ET_B receptor antagonist blocking the bindingof ET-1 to the receptors.² ET-1 is an isoform of endothelin found in human cardiovascular system. It acts through ET_A and ET_B  receptors and plays a key role in the regulation of blood pressure. Overexpression of both ET-1 and its receptors has been implicated in the pathogenesis of hypertension.³ Aprocitentan antagonizes these receptors and mitigates ET-1 mediated vasoconstriction to lower blood pressure.

Previously, some endothelin receptor antagonists were developed but didn’t significantly lower blood pressure which limited their utility. However, a phase III clinical trial using Aprocitentan was conducted. It showed improvements in blood pressure control among patients using the drug.⁴ The most frequent adverse effects found with the use of this drug were oedema and low RBC count. FDA approved this drug in March 2024 as an add-on therapyadd on therapy recognizing its potential. Nevertheless, data on its prolonged safety profile are scarce and additional research is vital to comprehensively assess its delayed complications.¹

Aprocitentan, in combination with other anti-hypertensives holds promise forin effectively treating resistant hypertension. It is essential for clinicians to remain informedregarding this drug in order to provide optimal care to patients. Health regulatory authorities should ensure that this revolutionary drug is available to those in need of it.