Parallel-Group, Phase 3 Study With Aprocitentan in Subjects With Resistant Hypertension - PRECISION

Nov 07, 2022
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Idorsia Pharmaceuticals and Janssen Biotech.
Date Presented:
11/07/2022
Date Published:
11/07/2022
Date Updated:
11/07/2022
Original Posted Date:
11/07/2022
References

Contribution To Literature:

The PRECISION trial showed that dual antagonism of the endothelin receptor improves blood pressure control in patients with resistant hypertension.

Description:

The goal of the trial was to evaluate aprocitentan compared with placebo among patients with resistant hypertension. Aprocitentan is a dual endothelinA/endothelinB receptor antagonist.

Study Design

  • Randomization
  • Parallel

Patients with resistant hypertension were randomized to aprocitentan 12.5 mg (n = 243) vs. 25 mg (n = 243) placebo (n = 244).

Eligible patients were started on a fixed-dose combination agent (amlodipine, valsartan, and hydrochlorothiazide; 5/160/25 mg or 10/160/25 mg) for a 4-week run-in phase. Patients who remained hypertensive were then randomized to aprocitentan 12.5 mg vs. aprocitentan 25 mg vs. placebo for 4 weeks (part 1 of the study). Patients were then given aprocitentan 25 mg for 32 weeks (part 2 of the study). Patients were then randomized to aprocitentan 25 mg vs. placebo for 12 weeks (part 3 of the study).

  • Total number of enrollees: 730
  • Duration of follow-up: 48 weeks
  • Mean patient age: 61 years
  • Percentage female: 41%
  • Percentage with diabetes: 52%

Inclusion criteria:

  • Systolic blood pressure ≥140 mm Hg despite use of ≥3 antihypertensive agents

Exclusion criteria:

  • Major cardiovascular, renal, or cerebrovascular problem within the past 6 months
  • New York Heart Association class III-IV heart failure
  • N-terminal pro-B-type natriuretic peptide levels ≥500 pg/mL

Principal Findings:

The primary outcome, change from baseline to week 4 (part 1 of the study) in mean systolic blood pressure, was: -3.8 mm Hg in the aprocitentan 12.5 mg group (p = 0.0042 vs. placebo) and -3.7 mm Hg in the aprocitentan 25 mg group (p = 0.0046 vs. placebo).

Secondary outcomes:

  • At week 40, systolic blood pressure remained stable with aprocitentan 25 mg, while it increased with placebo (-5.8 mm Hg, p < 0.0001 vs. placebo)
  • Edema/fluid retention: 9.1% with aprocitentan 12.5 mg vs. 18.4% with aprocitentan 25 mg vs. 2.1% with placebo

Interpretation:

Among patients with resistant hypertension, aprocitentan resulted in short-term and sustained blood pressure-lowering effects. Edema/fluid retention was more common with aprocitentan. Dual antagonism of the endothelin receptor may represent a new strategy in the treatment of resistant hypertension.

References:

Schlaich MP, Bellet M, Weber MA, et al., on behalf of the PRECISION investigators. Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomized, parallel-group, phase 3 trial. Lancet 2022;Nov 7:[Epub ahead of print].

Presented by Dr. Markus P. Schlaich at the American Heart Association Scientific Sessions, Chicago, IL, November 7, 2022.

Clinical Topics: Prevention, Statins, Hypertension

Keywords: AHA Annual Scientific Sessions, AHA22, Antihypertensive Agents, Blood Pressure, Diabetes Mellitus, Edema, Endothelin Receptor Antagonists, Hydrochlorothiazide, Hypertension, Primary Prevention, Receptors, Endothelin


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