Novel Dual Endothelin Inhibitors in the Management of Resistant Hypertension

Resistant hypertension (RH) is defined as the failure to achieve blood pressure control despite using triple combination therapy with a renin-angiotensin system inhibitor (RAS-i), a calcium antagonist, and a diuretic. The endothelin (ET) system is implicated in the regulation of vascular tone, primarily through vasoconstriction, intervenes in cardiac contractility with inotropic effects, and contributes to water and sodium renal reabsorption. ET inhibitors, currently approved for the treatment of pulmonary hypertension, seem to be also useful for essential hypertension and RH as well. Studies into the development of new dual ET inhibitors, which inhibit both type A and B ET (ETA and ETB) receptors, present initial results of managing RH. Aprocitentan (ACT-132577) is a novel, orally active and well tolerated dual ET receptor antagonist, which has been examined in several experimental studies and clinical trials with promising results for RH control. The recent publication of the large PRECISION study in The Lancet journal provides further reassurance regarding the efficacy and safety of aprocitentan for RH, with the aim of overcoming unmet needs in the management of this difficult group of patients.