Resistant hypertension is a pervasive problem among individuals with chronic kidney disease (CKD), resulting in a population of patients with a high risk for morbidity and mortality and limited treatment options. A post hoc analysis of the PRECISION (Parallel-Group, Phase 3 Study With Aprocitentan in Subjects With Resistant Hypertension) study by Patrick Rossignol, MD, PhD, and colleagues examined the efficacy and safety of aprocitentan with standardized background antihypertensive therapy as a treatment for these patients.

PRECISION comprised three parts: 4 weeks, double-blind (aprocitentan 12.5 and 25 mg versus placebo); 32 weeks, single-blind (aprocitentan 25 mg); and 12-weeks, double-blind withdrawal (aprocitentan 25 mg vs placebo).

The researchers assessed the safety of aprocitentan and its effects on BP and urinary albumin-creatinine ratio (UACR) among participants with CKD. Of the 730 total PRECISION participants, 147 had high-risk or very high-risk CKD as defined by KDIGO.

At week 4, office systolic BP declined by 13.5 mm Hg with aprocitentan 12.5 mg and by 16.6 mm Hg with aprocitentan 25 mg, compared with a reduction of 4.4 mm Hg with placebo. The reduction with aprocitentan 25 mg was sustained through week 36 (–16.4 mm Hg). At week 4, nighttime ambulatory sys­tolic BP fell by 9.6 mm Hg with aprocitentan 12.5 mg, by 13.8 mm Hg with aprocitentan 25 mg, and by 2.5 mm Hg with placebo.

At week 4, UACR decreased by 47.1% with aprocitentan 12.5 mg and by 59.6% with aprocitentan 25 mg, compared with a 2.4% reduction with placebo. The effect with aprocitentan 25 mg was maintained through week 36 (–61.6%). Aprocitentan was generally well tolerated, with no meaningful changes in potassium levels or eGFR. Early peripheral edema was the most common adverse event.

In summary, among patients with CKD and resistant hypertension, aprocitentan was well tolerated, reduced UACR, and lowered BP—with particular benefit for nighttime ambulatory BP. This suggests that the agent may offer substantial cardiovascular and renal-protective benefits to this patient population.