Endothelin receptor antagonism for resistant hypertension in chronic kidney disease: where does aprocitentan fit?
Key result
Aprocitentan 25 mg reduced office systolic blood pressure by 16.6 mmHg and urinary albumin/creatinine ratio by nearly 60% at 4 weeks in patients with resistant hypertension and kidney impairment.
Why the study?
Does aprocitentan reduce blood pressure and albuminuria in patients with resistant hypertension and chronic kidney disease?
Key Points
- To assess the efficacy and safety of aprocitentan, a dual endothelin receptor antagonist, in patients with resistant hypertension and chronic kidney impairment.
- Conducted a post hoc analysis of 147 participants with kidney impairment (baseline eGFR <60 ml/min/1.73 m², UACR ≥30 mg/g, or both) enrolled in the 48-week phase 3 PRECISION trial.
- Participants receiving standardized triple-combination background therapy were randomized to aprocitentan 12.5 mg, 25 mg, or placebo once daily during a 4-week double-blind phase (Part 1).
- At week 4, office systolic blood pressure fell by −13.5 (2.3) mmHg with 12.5 mg and −16.6 (1.9) mmHg with 25 mg compared to −4.4 (2.9) mmHg with placebo.
- UACR changed by −47.1% (95% CI −56.1 to −36.4) on 12.5 mg and −59.6% (−69.1 to −47.1) on 25 mg versus −2.4% (−24.4 to 26.1) on placebo.
- Peripheral edema developed in 37.9% (55/145) of patients, leading to treatment discontinuation in 2.1% (3/145), and 11 heart failure events were observed with none considered treatment-related.
Structured PICO
Does aprocitentan reduce blood pressure and albuminuria in patients with resistant hypertension and chronic kidney disease?
P
Population
147 participants (mean age 66.1 years, 29.3% female) with resistant hypertension and kidney impairment on fixed-dose triple-combination therapy, evaluated in a 48-week post hoc analysis.
I
Intervention
Aprocitentan 12.5 mg or 25 mg added to fixed-dose triple-combination background therapy (amlodipine 5 or 10 mg/valsartan 160 mg/hydrochlorothiazide 25 mg)
C
Comparator
Placebo added to fixed-dose triple-combination background therapy
O
Outcome
Changes in office systolic blood pressure (SBP), ambulatory blood pressure monitoring (ABPM) SBP, urinary albumin/creatinine ratio (UACR), eGFR, and hemoglobinsurrogate
Main Result
Absolute Event Rate: -16.6% vs -4.4%
Limitations
- Post hoc, non-prespecified analysis
- Not prospectively powered to assess CKD-specific efficacy or safety
- No data demonstrating improvement in hard cardiovascular or kidney outcomes
- Risk of fluid retention, edema, and anemia
- post hoc, non-prespecified analysis
- not prospectively powered to assess CKD-specific efficacy or safety
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“When you have resistant hypertension, you're more likely to have CKD, and when you have CKD, you're more likely to have resistant hypertension. This is a very difficult group to treat. Trying to get their blood pressure controlled is an important part of reducing their cardiovascular risk.”
Implication
Aprocitentan is a promising blood pressure-lowering agent for resistant hypertension in CKD, particularly when spironolactone is contraindicated, though careful volume management is essential due to edema risk.
Abstract
Emelina Stambolliu, Carmine Zoccali; Endothelin receptor antagonism for resistant hypertension in chronic kidney disease: where does aprocitentan fit?, Cli
Discussion
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Cite This Study
Stambolliu et al. (2026) conducted a review in Resistant hypertension in chronic kidney disease (n=147). Aprocitentan vs. Placebo was evaluated on Change in office systolic blood pressure from baseline to week 4. Aprocitentan 25 mg reduced office systolic blood pressure by 16.6 mmHg and urinary albumin/creatinine ratio by nearly 60% at 4 weeks in patients with resistant hypertension and kidney impairment.