Aprocitentan in Patients With Chronic Kidney Disease and Resistant Hypertension.

Summary

In CKD patients at high to very high KDIGO risk with resistant hypertension, aprocitentan achieved substantial office and nocturnal BP reductions and large, sustained decreases in urine albumin-to-creatinine ratio through 36 weeks, with good tolerability aside from early peripheral edema. These results suggest dual cardiovascular and renal benefits in a hard-to-treat population.

Key Findings

• At week 4, office SBP decreased by −13.5 mmHg (12.5 mg) and −16.6 mmHg (25 mg) versus −4.4 mmHg with placebo; the −16.4 mmHg reduction was maintained to week 36 on 25 mg.
• Nighttime ambulatory SBP fell by −9.6 and −13.8 mmHg (12.5/25 mg) vs −2.5 mmHg with placebo at week 4.
• Urine albumin-to-creatinine ratio decreased by −47.1% and −59.6% at week 4 vs −2.4% with placebo, sustained to −61.6% at week 36 on 25 mg.
• Aprocitentan was generally well tolerated without potassium or eGFR changes; early peripheral edema was the most common adverse event.

Clinical Implications

Consider aprocitentan as an add-on for resistant hypertension in CKD, with monitoring for early peripheral edema. Benefits in nocturnal BP and albuminuria may translate to improved cardiorenal outcomes; careful follow-up is warranted.

Limitations

• Post hoc subgroup analysis in CKD (not primary endpoint population)
• Single program dataset; long-term clinical outcome benefits not assessed

Future Directions

Prospective CKD-focused trials powered for cardiorenal outcomes and edema management strategies; mechanistic studies on endothelin blockade effects on albuminuria and nocturnal BP.