Aprocitentan in Patients With Chronic Kidney Disease and Resistant Hypertension

Area of Science:

• Nephrology
• Cardiology
• Pharmacology

Background:

• Hypertension and chronic kidney disease (CKD) are closely linked, with resistant hypertension being common and difficult to manage in CKD patients.
• Patients with CKD and resistant hypertension face high risks of morbidity and mortality, necessitating effective treatment options.

Purpose of the Study:

• To evaluate the efficacy and safety of aprocitentan in patients with CKD and resistant hypertension.
• To assess aprocitentan's impact on blood pressure, urine albumin-to-creatinine ratio, and overall safety profile.

Main Methods:

• Post hoc analysis of the PRECISION study involving 147 participants with KDIGO high or very high-risk CKD.
• Evaluation of aprocitentan (12.5 mg and 25 mg) versus placebo over 4 weeks, followed by extended treatment and withdrawal phases.

Main Results:

• Aprocitentan significantly reduced office systolic blood pressure (up to -16.6 mm Hg) and nighttime ambulatory systolic blood pressure (up to -13.8 mm Hg).
• Significant reductions in urine albumin-to-creatinine ratio were observed (up to -59.6%), maintained with continued aprocitentan treatment.
• Aprocitentan was well-tolerated, with no significant changes in potassium or estimated glomerular filtration rate; peripheral edema was the most common adverse event.

Conclusions:

• Aprocitentan demonstrated efficient blood pressure lowering, particularly nighttime ambulatory BP, and a marked reduction in albuminuria in CKD patients with resistant hypertension.
• The drug was well-tolerated and may offer significant cardiovascular and kidney-protective benefits for this challenging patient population.