Idorsia reports aprocitentan blood pressure reductions in patients with obesity and CKM stages 2 and 4a, alongside lower albuminuria. Long-term kidney benefits remain unproven.
Written By: Malavatu Satvika, PharmD
Reviewed By: Pharmacally Editorial Team
Idorsia reported findings from two post hoc analyses of the Phase 3 PRECISION trial evaluating aprocitentan in patients with resistant hypertension. Presented at the American Heart Association (AHA) Hypertension Scientific Sessions 2026 on October 10, the analyses examined treatment responses in patients with obesity and across cardiovascular-kidney-metabolic (CKM) stages. Both analyses reported reductions in office and ambulatory blood pressure, alongside changes in kidney-related biomarkers. However, the findings do not establish long-term kidney protection.
Blood Pressure Reductions in Patients with Obesity
The first analysis included 506 patients with obesity, defined as a body mass index (BMI) of at least 30 kg/m², and 224 patients without obesity. At Week 4, aprocitentan 12.5 mg and 25 mg reduced office systolic blood pressure by 15.4 mmHg and 16.0 mmHg, respectively, in patients with obesity.
Double-digit blood pressure reductions were maintained through Week 36, including the subsequent 32-week single-blind treatment period. Nighttime ambulatory systolic blood pressure also decreased, with reductions maintained during longer-term treatment.
The obesity subgroup had a greater burden of comorbidities, including diabetes, chronic kidney disease and cardiovascular conditions, despite similar baseline office blood pressure compared with patients without obesity. The findings suggest that blood pressure reductions were observed in patients with obesity and multiple comorbidities. However, the post hoc analysis does not establish that obesity modifies aprocitentan’s treatment effect or that the drug provides greater benefits in this subgroup.
Urinary albumin-to-creatinine ratio (UACR) decreased, estimated glomerular filtration rate (eGFR) remained stable, and uric acid showed favorable changes compared with placebo. The reported safety profile was consistent between patients with and without obesity.
Aprocitentan Across CKM Stages
The second analysis included 410 patients with CKM stage 2 and 273 patients with CKM stage 4a. These groups represented different levels of cardiometabolic disease burden, with patients in stage 4a having more comorbidities, including chronic kidney disease and cardiovascular conditions.
At Week 4, aprocitentan 12.5 mg reduced office systolic blood pressure by 15.1 mmHg in patients with CKM stage 2 and 16.6 mmHg in those with stage 4a. Daytime and nighttime ambulatory systolic blood pressure also decreased in both groups.
The findings indicate that blood pressure reductions were observed across these two CKM-stage groups, including patients with a greater burden of cardiometabolic disease. However, the numerical differences between the groups should not be interpreted as evidence of a stronger treatment response in stage 4a without a formal comparative analysis.
Among patients with albuminuria, UACR decreased by almost 50% across the two CKM stages. Uric acid showed favorable trends compared with placebo, while eGFR and N-terminal pro-B-type natriuretic peptide (NT-proBNP) remained stable. No increase in electrolyte abnormalities was reported, and the safety profile was consistent between the two groups.
The reduction in UACR is a potentially relevant finding because albuminuria is associated with kidney disease progression and cardiovascular risk. Nevertheless, a change in this biomarker does not demonstrate that aprocitentan prevents kidney function decline or cardiovascular events.
Mechanism and Clinical Context
Aprocitentan is a once-daily oral dual endothelin receptor antagonist that blocks endothelin-1 activity at ETA and ETB receptors. Endothelin-1 contributes to blood vessel constriction and blood pressure regulation.
Resistant hypertension refers to blood pressure that remains above target despite treatment with multiple antihypertensive medicines. The two analyses add subgroup-level evidence that aprocitentan can reduce blood pressure in patients with obesity and across CKM stages 2 and 4a.
Clinical Significance and Limitations
Both analyses were post hoc evaluations of the PRECISION trial, rather than separate trials prospectively designed to test these specific subgroups. Their findings should therefore be interpreted cautiously.
The reported blood pressure reductions provide the clearest evidence from these analyses. Changes in UACR and uric acid, together with stable eGFR and NT-proBNP, provide additional clinical context but do not establish long-term kidney or cardiovascular protection. Further research is needed to determine whether these biomarker changes translate into meaningful clinical outcomes.
Reference
Aprocitentan efficacy data reinforce endothelin pathway blockade as a distinct therapeutic approach across the cardiometabolic disease spectrum including obesity, Idorsia, 12 October 2026
A Research Study to Show the Effect of Aprocitentan in the Treatment of Difficult to Control (Resistant) High Blood Pressure (Hypertension) and Find Out More About Its Safety (PRECISION), ClinicalTrials.gov ID NCT03541174
About the Writer
Malavatu Satvika (Linkedin) is a Pharm.D professional and aspiring healthcare medical writer with clinical exposure and research experience. Her interests include medical writing, drug safety, pharmaceutical research, and evidence-based healthcare communication. She has contributed to two research publications in pharmaceutical journals and has gained practical experience in prescription review, patient counselling, medication review, adverse drug reaction monitoring, drug information services, literature review, and clinical documentation through regular hospital training.
She has completed certifications in clinical research, ICH-GCP E6(R3), data management for clinical research, and congenital hypothyroidism. With a strong foundation in pharmacy, clinical practice, and scientific research, she aims to translate complex medical and pharmaceutical information into accurate, clear, and evidence-based healthcare content. She is also preparing to pursue a PhD and further develop her expertise in medical writing and pharmaceutical research.