Aprocitentan in the treatment of resistant arterial hypertension: promising possibilities of endothelin-oriented therapy. Review

Abstract

Resistant arterial hypertension (RAH) remains one of the most challenging clinical problems in modern cardiology, especially among patients with concomitant type 2 diabetes mellitus, obesity, and chronic kidney disease (CKD). Despite the use of standard combination treatment regimens, a significant proportion of patients fail to achieve target blood pressure (BP) levels, thereby elevating cardiovascular and nephrological risk. Excessive activation of the endothelin system, particularly endothelin-1, plays a crucial role in the pathogenesis of RAH by promoting vasoconstriction, sodium retention, vascular remodelling, and progression of target organ damage. Aprocitentan, the first dual endothelin receptor (ETA and ETB ) antagonist approved for the treatment of RAH, introduces new opportunities for targeted pathogenetic therapy. This article summarises current data on the mechanisms of action, pharmacological properties, clinical efficacy, and safety of aprocitentan based on findings from the multicenter PRECISION trial. Aprocitentan has been shown to provide a sustained and clinically significant reduction in BP, including in elderly patients and those with CKD, with an acceptable safety profile. Thus, aprocitentan is considered a promising alternative or adjunct to standard treatment strategies for RAH, with potential cardio- and nephroprotective properties, paving the way for personalised antihypertensive therapy. Further long-term real-world studies are warranted to confirm its impact on cardiovascular risk and renal disease progression. Incorporation of endothelin receptor antagonism into contemporary treatment algorithms may significantly enhance risk stratification and optimisation of therapy in patients with true resistant hypertension, particularly in high-risk multimorbid populations.