Aprocitentan in Patients With Chronic Kidney Disease and Resistant Hypertension.

backgroundHypertension 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.

methodsThe 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.

resultsOf 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.

conclusionsAprocitentan 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.