Idorsia’s Phase 3 PRECISION study shows aprocitentan significantly reduces albuminuria and improves kidney risk categories in resistant hypertension, reinforcing benefits beyond blood pressure control.
Written By: Fariha Sameen, PharmD
Reviewed By: Pharmacally Editorial Team
Idorsia has presented new analyses from the Phase 3 PRECISION study (NCT03541174) showing that aprocitentan significantly reduced albuminuria and improved kidney risk categories in patients with resistant hypertension. Presented at the 35th Congress of the European Society of Hypertension (ESH), the findings provide new evidence that endothelin receptor blockade may address both blood pressure control and kidney risk in this high-risk population.
Mechanism and Background
Aprocitentan, marketed as TRYVIO® in the United States and JERAYGO® in Europe, is a dual endothelin receptor antagonist that blocks a pathway involved in vasoconstriction, inflammation, fibrosis, and organ damage. The endothelin system is often overactive in patients with resistant hypertension and chronic kidney disease (CKD).
Patients with resistant hypertension remain at increased risk of stroke, heart failure, CKD progression, and cardiovascular death despite treatment with multiple antihypertensive agents. Albuminuria, measured by urine albumin-creatinine ratio (UACR), is a recognized marker of kidney injury and a strong predictor of cardiovascular events and kidney failure.
Study Design and Results
The analysis included 730 patients with confirmed resistant hypertension receiving at least three antihypertensive medications, including a diuretic. Investigators assessed the effect of aprocitentan on albuminuria over 36 weeks.
Treatment produced rapid and substantial reductions in UACR. In patients with microalbuminuria, mean UACR declined from 77.5 mg/g to 34 mg/g by Week 36. Among those with macroalbuminuria, mean UACR fell from 860.2 mg/g to 286.7 mg/g.
Benefits emerged as early as Week 4. Up to 45% of patients with microalbuminuria achieved normal albumin levels, while up to 39% of patients with macroalbuminuria moved to a lower-risk category.
By Week 36, approximately 46% of patients with baseline micro- or macroalbuminuria had improved their albuminuria risk status.
Kidney function remained stable throughout treatment, with no decline in estimated glomerular filtration rate (eGFR). More than 92% of patients with normal baseline albumin levels maintained normal status during therapy.
Clinical Significance
Lead investigator Prof. Markus Schlaich said the findings demonstrate that aprocitentan not only delivers sustained blood pressure reductions but also produces meaningful improvements in albuminuria, an established marker of renal and cardiovascular risk.
The ability to move nearly half of high-risk patients into lower-risk albuminuria categories suggests the therapy could contribute to improved long-term renal and cardiovascular outcomes in patients whose hypertension remains difficult to control.
Supporting Evidence and Safety
The kidney findings complement previously reported PRECISION results showing durable double-digit reductions in systolic blood pressure maintained for up to 48 weeks across patient populations, including those with diabetes, CKD, obesity, and heart failure.
Aprocitentan demonstrated a manageable safety profile, with mild and transient edema as the most common treatment-related adverse event. Investigators observed no signal for hyperkalemia or hyponatremia.
Aprocitentan is approved in the United States, European Union, United Kingdom, and Switzerland, while regulatory review remains ongoing in Canada. The new kidney outcomes data expand the evidence base beyond blood pressure control and further support the potential role of endothelin pathway inhibition in resistant hypertension.
Reference
About the Writer
Fariha Sameen, PharmD (LinkedIn), is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.