Aprocitentan (Tryvio; Idorsia Pharmaceuticals), an endothelin receptor antagonist, can safely reduce blood pressure in patients with chronic kidney disease (CKD) and resistant hypertension, according to a post hoc analysis of the PRECISION trial.
When added to standard antihypertensive therapy, aprocitentan lowered both office and ambulatory blood pressure, with stronger effects at night. The drug also reduced urine albumin-to-creatinine ratio (UACR).
The findings, led by Patrick Rossignol, MD, PhD (Princess Grace Hospital, Monaco), were published online in Hypertension.
Aprocitentan was well-tolerated in this high-risk subgroup, with a safety profile similar to the overall trial population. No major changes in potassium, sodium, or estimated glomerular filtration rate (eGFR) were observed. Edema occurred in some patients, mainly within the first month of treatment, but was manageable.
“When you have resistant hypertension, you’re more likely to have CKD, and vice versa. This group is very difficult to treat,” said study co-author John Flack, MD (Southern Illinois University School of Medicine, Springfield). He emphasized that controlling blood pressure is crucial to reducing cardiovascular risk.
Flack noted that edema is manageable with careful patient selection and appropriate diuretic therapy. “I don’t view edema as a major problem,” he said.
PRECISION Trial Insights
Aprocitentan received FDA approval in March 2024 for patients whose hypertension is not adequately controlled by other medications. The drug reduced office and ambulatory blood pressure compared with placebo in patients on a fixed-dose combination of amlodipine, valsartan, and hydrochlorothiazide.
The post hoc analysis focused on 147 high- or very high-risk participants, representing 20% of the trial population, based on Kidney Disease Improving Global Outcomes (KDIGO) criteria. These patients were older (average age 66.1 vs. 60.6), more often male (70.7% vs. 56.6%) and Black (17.0% vs. 9.8%), and more likely to be on at least four antihypertensive medications (71.4% vs. 60.9%). They also had higher rates of diabetes and sleep apnea, but lower rates of heart failure.
Within this high-risk group, office systolic blood pressure dropped by 13.5 mm Hg with 12.5 mg and 16.6 mm Hg with 25 mg of aprocitentan over the first four weeks, compared with 4.4 mm Hg with placebo. The reduction with the 25 mg dose persisted over a 32-week single-blind period.
Daytime and nighttime ambulatory systolic blood pressure also declined, with larger decreases at night. After four weeks, nighttime blood pressure fell 9.6 mm Hg with 12.5 mg and 13.8 mm Hg with 25 mg of aprocitentan, versus 2.5 mm Hg with placebo.
UACR decreased by 47.1% and 59.6% with the lower and higher doses, respectively, while placebo showed a nonsignificant 2.4% reduction. The 25 mg effect persisted throughout the 32-week single-blind period. Blood pressure and UACR increased in patients switched to placebo during a withdrawal phase.
These benefits were consistent in patients with stage 3 or 4 CKD and in those with micro- or macroalbuminuria.
Safety Profile
The most common adverse event was edema, usually mild or moderate and often manageable with diuretics. Among high-risk patients, 37.9% experienced at least one edema episode, higher than the 25.4% in the overall trial. Edema primarily occurred within the first four weeks of treatment.
Eleven patients experienced heart failure events, with seven requiring hospitalization, but none were considered related to the drug.
Expert Perspectives
George Thomas, MD (Cleveland Clinic), said CKD patients with resistant hypertension are among the hardest to treat. “The challenge is to use agents that do not harm kidney function or cause hyperkalemia,” he said.
In this subgroup, aprocitentan produced durable blood pressure reductions without affecting kidney function or potassium levels. Edema remains a concern, particularly in advanced CKD or patients with heart failure.
Flack added that earlier adoption of aprocitentan was limited by the FDA’s risk evaluation and mitigation strategy, which was lifted in April. He recommended avoiding the drug in patients with heart failure or severe edema. “For most patients with resistant hypertension and CKD, aprocitentan is an acceptable and attractive option,” he said.
Related topic：
