ESC Congress 2025 - KARDIA 3 finds that a single dose of zilebesiran 300mg reduced office systolic blood pressure at month three compared to placebo, informing the dose, design and patient population for the upcoming zilebesiran phase III Cardiovascular outcomes trial.

Dr Neha Pagidipati (Duke University Medical Center, US) joins us to discuss findings from the KARDIA-3 trial, evaluating zilebesiran as add-on therapy in patients with high cardiovascular risk and hypertension not adequately controlled by standard antihypertensive medications.

This randomized, double-blind, placebo-controlled multicenter study represents a significant advancement in hypertension management, investigating the efficacy and safety of zilebesiran - a novel RNA interference therapeutic targeting angiotensinogen production. The trial enrolled 270 patients with elevated cardiovascular risk whose blood pressure remained uncontrolled despite treatment with 2-4 standard antihypertensive medications, addressing a critical unmet need in clinical practice. Participants received a single subcutaneous injection of zilebesiran or placebo on Day 1, followed by a 6-month double-blind treatment period. The primary endpoint measured change from baseline in mean seated office systolic blood pressure at Month 3, providing insights into the sustained efficacy of this once-dosing therapeutic approach.

Findings showed that a single dose of zilebesiran 300mg led to a 5-mmHg reduction in SBP at 3 months when compared to placebo. This did not achieve statistical significance, though the trial met its objective, informing the design of upcoming trials.

Interview Questions:

1. What is the reasoning behind this study?
2. What was the study design and patient population?
3. What were the key findings from KARDIA-3?
4. What are the implications of these findings for clinical practice?
5. What are the next steps?

Recorded on-site at ESC Congress 2025, Madrid.

Editors: Jordan Rance, Yazmin Sadik.
Videographers: Mike Knight, Dan Brent, Oliver Miles, Tom Green, David-Ben-Harosh.
Support: This is an independent interview produced by Radcliffe Cardiology.