Zilebesiran in Combination With a Standard-of-Care Antihypertensive in Patients With Inadequately Controlled Hypertension - KARDIA-2

Apr 07, 2024
Font Size
A
A
A
Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Date Presented:
04/07/2024
Date Published:
04/07/2024
Original Posted Date:
04/07/2024
References

Contribution To Literature:

The KARDIA-2 trial showed that subcutaneous injection of zilebesiran improves blood pressure reduction to 6 months.

Description:

The goal of the trial was to evaluate zilebesiran compared with placebo among patients with uncontrolled hypertension. Zilebesiran is a subcutaneously injected RNA interference agent that targets hepatic synthesis of angiotensinogen (AGT), which is the most upstream precursor of all angiotensin peptides.

Study Design

  • Randomized
  • Parallel
  • Blinded
  • Placebo
  • Phase 2

Patients with uncontrolled hypertension were randomized to zilebesiran vs. placebo after a run-in period where they received indapamide 2.5 mg daily, or amlodipine 5 mg daily, or olmesartan 40 mg daily.

  • Total number of enrollees: 1,500
  • Duration of follow-up: 6 months
  • Mean patient age: 59 years
  • Percentage female: 43%
  • Percentage with diabetes: 23%

Inclusion criteria:

  • 18-75 years of age
  • Untreated systolic blood pressure 155-180 mm Hg, or
  • Treated systolic blood pressure 145-180 mm Hg

Other salient features/characteristics:

  • Mean 24-hour ambulatory systolic blood pressure: 143 mm Hg

Principal Findings:

The primary outcome, change from baseline to 3-month 24-hour mean ambulatory systolic blood pressure, was -12.1 mm Hg in the indapamide group for zilebesiran vs. placebo (p < 0.001), -9.7 mm Hg in the amlodipine group for zilebesiran vs. placebo (p < 0.001), and -4.0 mm Hg in the olmesartan group for zilebesiran vs. placebo (p = 0.036). The blood pressure difference was sustained to 6 months in the indapamide and amlodipine groups.

Secondary outcomes:

  • Change from baseline to 3-month office systolic blood pressure: -18.5 mm Hg in the indapamide group for zilebesiran vs. placebo (p < 0.001), -10.2 mm Hg in the amlodipine group for zilebesiran vs. placebo (p < 0.001), and -7.0 mm Hg in the olmesartan group for zilebesiran vs. placebo (p < 0.001)
  • No deaths or no adverse events leading to study discontinuation

Interpretation:

Among patients with uncontrolled hypertension, subcutaneous injection of zilebesiran improves 3-month blood pressure control, especially among those treated with indapamide and amlodipine. Systolic blood pressure control was sustained to 6 months in the indapamide and amlodipine groups, but not in the olmesartan group. Zilebesiran was well tolerated during the study period. Zilebesiran represents a novel treatment for uncontrolled hypertension.

References:

Presented by Dr. George L. Bakris at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 7, 2024.

Clinical Topics: Prevention, Hypertension, Vascular Medicine

Keywords: ACC24, ACC Annual Scientific Session, Hypertension, Novel Agents, RNA Interference


< Back to Listings