Kidney Week

Abstract: SA-PO356

Incidence and Prevalence of Edema and the Effect of Aprocitentan Treatment Strategy in the PRECISION Study

Session Information

• Hypertension, CVD, and the Kidneys: Clinical Research
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1602 Hypertension and CVD: Clinical

Authors

• Schlaich, Markus P., The University of Western Australia Medical School, Perth, Western Australia, Australia

Markus P. Schlaich, MD

• Bakris, George L., The University of Chicago Medicine, Chicago, Illinois, United States

George L. Bakris, MD, MA, FASN

• Danaietash, Parisa, Idorsia Pharmaceuticals Ltd, Allschwil, Basel-Landschaft, Switzerland

Parisa Danaietash, PhD

• Flamion, Bruno, Idorsia Pharmaceuticals Ltd, Allschwil, Basel-Landschaft, Switzerland

Bruno Flamion, MD, PhD

• Narkiewicz, Krzysztof, Medical University of Gdansk Department of Hypertension and Diabetology, Gdansk, Poland

Krzysztof Narkiewicz, MD, PhD

• Sassi-Sayadi, Mouna, Idorsia Pharmaceuticals Ltd, Allschwil, Basel-Landschaft, Switzerland

Mouna Sassi-Sayadi, MS

• Wang, Jiguang, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China

Jiguang Wang, MD, PhD

• Weber, Michael A., SUNY The State University of New York, New York, New York, United States

Michael A. Weber, MD

Background

Edema is an expected adverse event with Endothelin Receptor Antagonists (ERAs). PRECISION evaluated the effect of aprocitentan (APRO), a dual ERA in patients with resistant hypertension and increased CV risk (54% diabetes, 22% renal insufficiency, 20% history of heart failure). All patients were on a standardized fixed-dose combination of amlodipine (71% of patients at 10 mg), valsartan and hydrochlorothiazide. Results from PRECISION indicated a lower edema incidence in patients on 12.5 mg vs 25 mg APRO during the first 4 weeks. The objective of this analysis was to evaluate whether 12.5 mg APRO for 4 weeks followed by 25 mg APRO (12.5/25) decreased edema risk compared with 25 mg as initial dosing and throughout the study (25/25).

Methods

The study design included 3 parts: Part 1: double-blind placebo-controlled 12.5 mg or 25 mg APRO, or placebo for 4 weeks; Part 2: prolonged single-blind administration of 25 mg APRO to all patients; Part 3: double-blind placebo-controlled withdrawal phase (25 mg APRO vs placebo). Incidence (new and recurrent onset) and prevalence (new and ongoing events) of AEs indicating edema were evaluated up to 48 weeks by treatment regimen: a) 12.5/25 cohort or b) 25/25 cohort.

Results

The incidence of edema was lower in the 12.5 mg group (9.1%) vs the 25 mg group (15.9%) during the first 4 weeks of treatment (Fig 1). Most new events occurred during the first 8 weeks of treatment. After that, the incidence of edema in both APRO treatment sequences was comparable with the range reported for the placebo group during the first 4 weeks of treatment. The prevalence of edema during the 48-week study was consistently lower in subjects in the 12.5/25 cohort (11% to 17%) vs those in the 25/25 cohort (16% to 21%) throughout the study.

Conclusion

Initiation therapy with 12.5 mg APRO may represent a preferred clinical approach particularly in patients with risk of edema.

Figure 1: Incidence of edema in PRECISION

Funding

• Commercial Support – Idorsia Pharmaceuticals Ltd.