Aprocitentan: The First Endothelin Receptor Antagonist for Resistant Hypertension

Area of Science:

• Pharmacology
• Cardiovascular Medicine
• Clinical Trials

Background:

• Resistant hypertension affects individuals whose blood pressure remains uncontrolled despite optimal treatment with at least three different antihypertensive medications.
• Aprocitentan, a novel dual endothelin receptor antagonist (ETa and ETb), was approved in early 2024 for treating hypertension inadequately controlled by existing therapies.

Purpose of the Study:

• To evaluate the efficacy and safety of aprocitentan in adult patients with resistant hypertension.
• To assess the blood pressure-lowering effects of aprocitentan compared to placebo in a large, multicenter study.

Main Methods:

• A phase 3, multicenter study randomized 730 adult patients with systolic blood pressure ≥140 mm Hg to receive either placebo or aprocitentan (12.5 mg or 25 mg) alongside their existing antihypertensive medications.
• Patients underwent a run-in period with placebo and continued standard background therapy throughout the study.

Main Results:

• Aprocitentan 12.5 mg demonstrated superiority over placebo in reducing sitting systolic blood pressure at week 4.
• The blood pressure-lowering effect of aprocitentan was sustained, with statistically significant results observed at week 40 when patients on 25 mg were rerandomized to placebo.

Conclusions:

• Aprocitentan is a novel endothelin receptor antagonist offering a new therapeutic option for patients with resistant hypertension.
• The drug shows sustained efficacy in lowering blood pressure, addressing a critical unmet need in managing difficult-to-control hypertension.