Abstract: FR-OR96
Effects of Aprocitentan for Blood Pressure Lowering and Proteinuria in Patients with CKD and Resistant Hypertension
Session Information
- Novel Clinical Impacts on Cardiorenal Disease
November 03, 2023 | Location: Room 103, Pennsylvania Convention Center
Abstract Time: 05:15 PM - 05:24 PM
Category: Hypertension and CVD
- 1602 Hypertension and CVD: Clinical
Authors
- Bakris, George L., University of Chicago Medicine, Chicago, Illinois, United States
- Flack, John M., Southern Illinois University School of Medicine, Springfield, Illinois, United States
- Narkiewicz, Krzysztof, Medical University of Gdansk, Gdansk, Poland
- Schlaich, Markus P., University of Western Australia, Perth, New South Wales, Australia
- Wang, Jiguang, Jiaotong University School of Medicine, Shanghai, China
- Weber, Michael A., State University of New York, Brooklyn, New York, United States
- Sassi-Sayadi, Mouna, Idorsia Pharmaceuticals, Ltd, Allschwil, Switzerland
- Haskell, Lloyd P., Janssen Research & Development, LLC, Raritan, New Jersey, United States
- Flamion, Bruno, Idorsia Pharmaceuticals, Ltd, Allschwil, Switzerland
Background
Hypertension is often difficult to control in patients with CKD. In the phase 3 PRECISION trial, the dual endothelin receptor antagonist aprocitentan (APRO) at 12.5 and 25mg once-daily demonstrated significant BP reductions vs placebo (PBO) in patients with resistant hypertension. We evaluated APRO in patients with CKD enrolled in PRECISION.
Methods
Participants had unattended automated office systolic BP (SBP) ≥140mmHg despite use of ≥3 antihypertensive drugs. This subgroup analysis included patients with an eGFR of 15 to <60mL/min/1.73m2. Reductions in office SBP, ambulatory BP monitoring (ABPM), and urinary albumin-to-creatinine ratio (UACR) were assessed following the double-blind treatment phase (Week 4), after 32-week single-blind APRO 25mg treatment (Week 36), and after 4 weeks of randomized withdrawal (Week 40).
Results
Changes in office BP and UACR in 162 CKD patients included in this analysis are summarized in the table below. Both doses of APRO resulted in a more pronounced BP reduction from baseline to week 4 compared to PBO. This was confirmed by ABPM.
At Week 4, edema or fluid retention occurred in 18% and 24% of patients receiving APRO 12.5mg and 25mg, respectively, vs 2% with PBO; this rate was 34% in subjects exposed to APRO 25 mg during the trial. 55% of them were treated with diuretics (90% loop); 2 discontinued treatment due to this event. Five patients receiving APRO 25mg and 1 receiving placebo had heart failure leading to hospitalization; all but one had a history of heart disease.
Conclusion
In patients with CKD stage 3 or 4 and resistant hypertension, APRO 12.5 and 25mg added to ≥3 antihypertensive drugs resulted in a substantial reduction of both office and ambulatory BP and UACR. Edema and fluid retention were manageable with additional diuretics.
| (mean values) | APRO 12.5mg | APRO 25mg | PBO |
| Baseline Office SBP (mmHg) | 154.1 | 153.5 | 154.7 |
| Week 4 Office SBP (mmHg) | 140.6 | 134.6 | 148.0 |
| Week 36 Office SBP (mmHg) | Not applicable | 134.8 | Not applicable |
| Week 40 Office SBP (mmHg) | Not applicable | 136.1 | 143.5 |
| Baseline UACR (mg/g) | 109.2 | 63.4 | 114.9 |
| Week 4 UACR (ratio from baseline) | 0.72 | 0.56 | 0.96 |
| Week 36 UACR (ratio from baseline) | Not applicable | 0.50 | Not applicable |
Funding
- Commercial Support – Janssen Pharmaceuticals and Idorsia Pharmaceuticals, Ltd