Vnitr Lek 2026, 72(6):E16-E20 | DOI: 10.36290/vnl.2026.079
Aprocitentan - a dual endothelin receptor antagonist for the treatment of resistant arterial hypertension
- II. interní klinika LF a FN v Plzni
Aprocitentan is a dual endothelin receptor inhibitor and a new drug approved in both the U.S. and Europe for the treatment of resistant hypertension. It is distinctive in that it targets a pathophysiological mechanism that is not affected by any existing antihypertensive medications. Unlike first-generation endothelin receptor blockers, it is not metabolized by CYP450 or BcRP, which means a lower risk of drug interactions. Current evidence demonstrates a significant reduction in blood pressure, both clinical and 24-hour, including sustained reductions during the night. In the PRECISION study, the difference in blood pressure reduction in patients treated with aprocitentan at doses of 12.5 and 25 mg compared with placebo was -4.2 mm Hg (95% CI -6.2 to -2.1) and -5.9 mm Hg (-7.9 to 3.8) for 24-hour systolic blood pressure. However, long-term data on its safety are still lacking, and, above all, evidence of its effect on reducing cardiovascular complications is missing. The most common adverse effects are fluid retention, the development of edema, and the onset of mild anemia.
Keywords: aprocitentan, dual endothelin receptor inhibitor, arterial hypertension, resistant hypertension.
Accepted: September 16, 2026; Published: October 2, 2026 Show citation
References
- Widimský J, et al. Diagnostické a léčebné postupy u arteriální hypertenze - verze 2022. Doporučení České společnosti pro hypertenzi. Hypertenze Kardiovaskulární Prevence. 2022;2 (supplementum):1-25
- Nishiyama SK, et al. Vascular function and endothelin-1: tipping the balance between vasodilation and vasoconstriction. Journal of Applied Physiology. 2017;122(2):354-360.
Go to original source... - Vignon-Zellweger P, et al. Endothelin and endothelin receptors in the renal and cardiovascular systems. Life science. 2012;91:490-500.
Go to original source...
Go to PubMed... - Wei A, et al. Clinical Adverse Effects of Endothelin Receptor Antagonists: Insights From the Meta-Analysis of 4894 Patients From 24 Randomized Double-Blind Placebo-Controlled Clinical Trials. Journal of the American Heart Association. 2016;5(11):e003896.
Go to original source...
Go to PubMed... - Bakris GL, et al. Divergent Results Using Clinic and Ambulatory Blood Pressures. Report of a Darusentan-Resistant Hypertension Trial. Hypertension. 2010;56(5):824-830.
Go to original source...
Go to PubMed... - Sidharta PN, et al. Single- and multiple-dose tolerability, safety, pharmacokinetics, and pharmacodynamics of the dual endothelin receptor antagonist aprocitentan in healthy adult and elderly subjects. Drug Des Devel Ther. 2019;13:949-964.
Go to original source... - Angeli F, Verdecchia P, Reboldi G. Aprocitentan, A Dual Endothelin Receptor Antagonist Under Development for the Treatment of Resistant Hypertension. Cardiol Ther. 2021;10(2):397-406.
Go to original source... - Sidharta PN, Ulč I, Dingemanse J. Single-Dose Pharmacokinetics and Tolerability of Aprocitentan, a Dual Endothelin Receptor Antagonist, in Subjects with Severe Renal Function Impairment. Clinical Drug Investigation. 2019;39(11):1117-1123.
Go to original source...
Go to PubMed... - Schlaich MP, et al. Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial. The Lancet. 2022;400(10367):1927-1937.
Go to original source...
Go to PubMed... - Rahimi K, et al. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. The Lancet. 2021;397(10285):1625-1636.
Go to original source...
Go to PubMed... - Mancia G, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension Endorsed by the European Renal Association (ERA) and the International Society of Hypertension (ISH). J Hypertens. 2023;J Hypertens. 2023;41(12):1874-2071.
Go to original source...
Go to PubMed... - McEvoy JW, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024;45(38):3912-4018.
Go to original source...
Go to PubMed... - Williams B, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;386(10008):2059-68.
Go to original source...
Go to PubMed... - TRYVIO FDA. 2024.
- Danaietash P, et al. Identifying and treating resistant hypertension in PRECISION: A randomized long-term clinical trial with aprocitentan. J Clin Hypertens (Greenwich). 2022;24(7):804-813.
Go to original source...




