Jan Kalinowski, Wojciech Świgut, Miłosz Miedziaszczyk, Ilona Idasiak-Piechocka
Aprocitentan for the treatment of resistant hypertension
2026-06-19
Subject of study. Hypertension is one of the most common chronic diseases and one of the most important factors responsible for the development and progression of chronic kidney disease (CKD). In patients with impaired renal function, a particular clinical problem remains resistant arterial hypertension (RHT), defined as failure to achieve target blood pressure despite appropriate antihypertensive therapy involving at least three medications, including a diuretic. It is estimated that RHT occurs in over 20% of patients with CKD. Inadequate blood pressure control is associated with an increased risk of cardiovascular complications, accelerated renal function loss, and worsening albuminuria. The pathogenesis of RHT in patients with CKD is complex and includes, among other factors, sodium and water retention, excessive activation of the renin-angiotensin-aldosterone system (RAAS), increased sympathetic nervous system activity, and increased expression of endothelin-1, which plays a significant role in vasoconstriction, inflammation, and vascular remodeling.
Research objective. The aim of this study was to analyze current data regarding the role of aprocitentan – a new dual antagonist of the endothelin receptors ETA and ETB – in the treatment of resistant hypertension in patients with chronic kidney disease. Particular attention was paid to the drug’s mechanism of action, its antihypertensive efficacy, safety, and the potential clinical benefits of endothelin pathway-targeted therapy in the CKD population.
Material and methods. Analysis of available literature data, including preclinical and clinical studies on the use of aprocitentan in patients with resistant hypertension, with particular emphasis on patients with chronic kidney disease, was conducted. The results of studies evaluating the drug’s antihypertensive efficacy, effects on renal parameters, pharmacokinetic profile, safety, and the possibility of using aprocitentan in combination with standard treatment based on RAAS inhibitors, calcium channel blockers, and diuretics were assessed.
Results. Analysis of the available data indicates that aprocitentan is a promising therapeutic option for the treatment of resistant hypertension. Preclinical studies have demonstrated its high efficacy in low-renin hypertension models characteristic of advanced chronic kidney disease (CKD) and a more favorable renal profile compared to spironolactone used in combination with RAAS inhibitors. Results from the PRECISION clinical trial confirmed significant reductions in blood pressure in patients with RHT, with the greatest benefits observed in patients with CKD stages 3-4 and concomitant macroalbuminuria. The antihypertensive effect was maintained during long-term follow-up. Aprocitentan also exhibits stable pharmacokinetics regardless of the degree of renal impairment, a low potential for drug interactions, and the potential for once-daily dosing, which promotes patient compliance.
Conclusions. Aprocitentan is a new and promising treatment option for resistant hypertension in patients with CKD. Its mechanism of action, based on blocking endothelin receptors, allows it to be an effective adjunct to standard antihypertensive therapy, particularly in patients whose blood pressure is not adequately controlled despite treatment according to current guidelines. Current study results indicate a favorable efficacy and safety profile for the drug, particularly in patients with advanced CKD. However, further studies are needed to assess the effect of aprocitentan on the rate of renal disease progression, reduction of albuminuria, and long-term cardiovascular outcomes.
Keywords: Antihypertensive Agents, Resistant hypertension, Endothelin Receptor Antagonists.
© Farm Pol, 2025, 81(12): 711–720