Objective: This article reviews the published data including the pharmacology, efficacy, and safety of aprocitentan, a novel endothelin receptor antagonist developed to treat hypertension in conjunction with additional agents.

Data sources: A literature search was conducted from drug discovery until May 2024 through PubMed, MEDLINE, and National Institutes of Health Clinical Trials Registry utilizing the following search terms: Tryvio, aprocitentan, hypertension, resistant hypertension, endothelin receptor antagonist, and ACT-132577.

Study selection and data extraction: All relevant English-language studies, or studies that could be appropriately translated into English, containing the pharmacology, pharmacokinetics, safety, and efficacy of aprocitentan, were selected for review.

Data synthesis: In the setting of resistant hypertension, aprocitentan has shown significant reductions in blood pressure in both medical office and 24-hour ambulatory settings at 4 weeks with a sustained effect at 40 weeks. Studies evaluating cardiovascular risk reduction have not been conducted at this time. Fluid retention and edema were the most frequent adverse events reported in clinical studies with aprocitentan. As a class, endothelin receptor antagonists may cause fetal harm; aprocitentan should be used with caution to avoid embryo-fetal toxicity.

Relevance to patient care and clinical practice in comparison to existing drugs: Owing to the existent barriers for the treatment of resistant hypertension, aprocitentan presents itself as an effective option when added to traditional antihypertensives. This single-strength, once-daily regimen may serve as an appealing option to both patients and prescribers.

Conclusion: Aprocitentan is a safe and effective medication for the treatment of hypertension when added to other pharmacological therapies.