Aprocitentan in Patients With Chronic Kidney Disease and Resistant Hypertension

Abstract

BACKGROUND: Hypertension is a cause and consequence of chronic kidney disease (CKD). Resistant hypertension is common and often difficult to control in patients with CKD. This post hoc analysis evaluated the efficacy and safety of aprocitentan (with standardized background antihypertensive therapy) in patients with CKD and resistant hypertension, a group with high morbidity and mortality risk and limited treatment options. METHODS: The PRECISION study (Parallel-Group, Phase 3 Study With Aprocitentan in Subjects With Resistant Hypertension) consisted of part 1: 4-week, double-blind (aprocitentan 12.5 and 25 mg versus placebo); part 2: 32-week, single-blind (aprocitentan 25 mg); and part 3: 12-week, double-blind withdrawal (aprocitentan 25 mg versus placebo). In participants with CKD, aprocitentan’s effect on blood pressure (BP), urine albumin-to-creatinine ratio, and safety was evaluated. RESULTS: Of 730 participants in PRECISION, 147 had CKD categorized as KDIGO high risk or very high risk. At week 4, aprocitentan 12.5 mg, aprocitentan 25 mg, and placebo reduced office systolic BP by −13.5, −16.6, and −4.4 mm Hg, respectively; this was maintained with aprocitentan 25 mg to week 36 (−16.4 mm Hg). At week 4, reductions in nighttime ambulatory systolic BP were −9.6, −13.8, and −2.5 mm Hg, respectively. Changes in urine albumin-to-creatinine ratio were −47.1%, −59.6%, and −2.4%, respectively, maintained with aprocitentan 25 mg to week 36 (−61.6%). Aprocitentan was generally well tolerated (no change in potassium or estimated glomerular filtration rate); early peripheral edema was the most common adverse event. CONCLUSIONS: Aprocitentan was well tolerated; efficiently lowered BP, particularly nighttime ambulatory BP; and markedly reduced urine albumin-to-creatinine ratio in participants with CKD and resistant hypertension. Aprocitentan may confer considerable cardiovascular and kidney-protective benefits in these difficult-to-treat patients. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03541174.

Affiliated Institutions

• Princess Grace Hospital Centre MC
• Southern Illinois University School of Medicine US
• Universitätsklinikum Erlangen DE
• SUNY Downstate Health Sciences University US
• Université de Lorraine FR
• Inserm FR
• Gdańsk Medical University PL
• Centre Hospitalier Régional et Universitaire de Nancy FR
• French Clinical Research Infrastructure Network FR
• Royal Perth Hospital AU
• Tris Pharma (United States) US
• Hospital Research Foundation AU
• The University of Western Australia AU
• State University of New York US
• Shanghai Institute of Hypertension CN
• Idorsia (Switzerland) CH

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