Aprocitentan for Blood Pressure Reduction in Black Patients

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 82; no. 4; pp. 601 - 610
• Main Authors: Flack, John M., Schlaich, Markus P., Weber, Michael A., Sassi-Sayadi, Mouna, Narkiewicz, Krzysztof, Clozel, Martine, Dreier, Roland F., Andrawis, Nabil S., Danaietash, Parisa, Gabra, Nashwa, Scott, David, Wang, Ji-Guang, Ferdinand, Keith C.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.04.2025
• Subjects: Adult; Aged; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - adverse effects; Antihypertensive Agents - therapeutic use; Black or African American; Black People; Blood Pressure - drug effects; Blood Pressure - physiology; Blood Pressure Monitoring, Ambulatory; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypertension - drug therapy; Hypertension - ethnology; Hypertension - physiopathology; Male; Middle Aged; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Sulfonamides - administration & dosage; Sulfonamides - therapeutic use; Treatment Outcome; White; aprocitentan; endothelin receptor antagonists; blood pressure; edema; hypertension
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.124.24142

BACKGROUND: Black individuals frequently present with resistant hypertension and disproportionately increased cardiovascular risk. We investigated the blood pressure (BP)-lowering effect of the dual endothelin receptor antagonist aprocitentan in Black individuals enrolled in the PRECISION study (Parallel-Group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension). METHODS: Patients with confirmed resistant hypertension were randomized to aprocitentan 12.5 mg, 25 mg, or placebo for 4 weeks (part 1). They subsequently received aprocitentan 25 mg for 32 weeks (part 2) before re-randomization to aprocitentan 25 mg or placebo (part 3). RESULTS: Eighty-two patients randomized in the PRECISION study were Black individuals. At week 4, aprocitentan 12.5 and 25 mg reduced office trough systolic BP (−11.3 and −11.9 mm Hg) to a similar degree as placebo (−12.0 mm Hg). Using 24-hour ambulatory BP monitoring, the placebo effect was minimal (−0.7 mm Hg), and aprocitentan reduced systolic BP by 4.0 and 8.6 mm Hg. During part 2, office BP continued to decrease (−16.4 mm Hg at week 36). In part 3, office and ambulatory systolic BP increased on placebo (+9.9 and +8.1 mm Hg, respectively), whereas the BP-lowering effect was maintained with aprocitentan. Aprocitentan markedly reduced albuminuria during the study. The most frequent adverse event was peripheral edema, occurring in 3 patients (10%) receiving aprocitentan 25 mg versus none receiving aprocitentan 12.5 mg or placebo. CONCLUSIONS: Aprocitentan reduced BP and albuminuria in Black individuals with resistant hypertension. The BP-lowering efficacy was similar to that of the overall PRECISION population. Aprocitentan may represent an important addition to the often difficult-to-control hypertension in Black individuals. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03541174.