Aprocitentan effective for BP lowering in patients with CKD and resistant hypertension

"The addition of APRO 12.5 and 25mg to ≥3 antihypertensive drugs resulted in a substantial reduction of both ambulatory and office BP and urinary albumin-to-creatinine ratio (UACR) in patients with CKD stage 3 or 4 and resistant hypertension," the researchers reported. The findings were presented at the Kidney Week 2023, organized by the American Society of Nephrology, by George Bakris, Professor and director of the Comprehensive Hypertension Center at the University of Chicago.

In patients with chronic kidney disease, hypertension is often difficult to control. In the phase 3 PRECISION trial, the dual endothelin receptor antagonist aprocitentan at 12.5 and 25mg once daily showed significant reductions in blood pressure versus placebo (PBO) in resistant hypertension patients. In the study, the researchers evaluated APRO in patients with CKD enrolled in PRECISION.

Participants had unattended automated office systolic BP (SBP) ≥140mmHg despite the use of ≥3 antihypertensive drugs. This subgroup analysis included patients with an eGFR of 15 to <60mL/min/1.73m2.

The researchers assessed reductions in ambulatory BP monitoring (ABPM), office SBP, and UACR following the double-blind treatment phase (Week 4), after 32-week single-blind APRO 25mg treatment (Week 36), and after 4 weeks of randomized withdrawal (Week 40).

Based on the study, the researchers reported the following findings:

• Both doses of APRO resulted in a more pronounced BP reduction from baseline to week 4 compared to PBO. This was confirmed by ABPM.
• At Week 4, edema or fluid retention occurred in 18% and 24% of patients receiving APRO 12.5mg and 25mg, respectively, vs 2% with PBO; this rate was 34% in subjects exposed to APRO 25 mg during the trial.
• 55% of them were treated with diuretics (90% loop); 2 discontinued treatment due to this event.
• Five patients receiving APRO 25mg and 1 receiving a placebo had heart failure leading to hospitalization; all but one had a history of heart disease.

The findings support the potential use of aprocitentan in patients with BP that remains elevated despite treatment with three established antihypertensive drug classes and with stage 3 CKD with an eGFR of 30-59 mL/min per 1.73 m2 if approved for U.S. marketing in 2024.

"This is a key group of patients because "CKD is the most common comorbidity in patients with resistant hypertension," the researchers concluded.

Reference:

ABSTRACT: FR-OR96 Effects of Aprocitentan for Blood Pressure Lowering and Proteinuria in Patients with CKD and Resistant Hypertension