George L. Bakris, MD
Image source: American Heart Association
A single dose of zilebesiran can safely and effectively reduce systolic blood pressure in patients with mild to moderate hypertension for up to 6 months, according to new findings from the KARDIA Phase 2 study.1
The latest study, presented at the 2023 American Heart Association (AHA) Scientific Sessions in Philadelphia, Pennsylvania, showed that patients who received a single dose of zilbesiland achieved a mean reduction in 24-hour systolic blood pressure of ≥10 mmHg compared to Below, placebo.
“Uncontrolled hypertension is a leading cause of death and disease, so new treatments are needed to sustain blood pressure control over the long term. This will improve outcomes for patients with hypertension,” said lead author, Professor of Medicine and Comprehensive Hypertension Center at the University of Chicago Director George L. Bakris, MD, said in a statement.1
Uncontrolled high blood pressure is associated with an increased risk of heart disease. Heart disease remains the leading cause of death in the United States, and about half of adults in the United States have high blood pressure, according to the American Heart Association’s 2023 statistical update.2 Zilebesiran is an investigational RNA interference agent that targets angiotensinogen (AGT), a hormone produced primarily in the liver that helps regulate blood pressure.1
The KARDIA Phase 2 study is a global, placebo-controlled, randomized, double-blind trial evaluating the safety and efficacy of zilebesiline in patients with mild to moderate hypertension (systolic blood pressure 135-160 mmHg). Effectiveness, in those who are untreated or on stable therapy with ≤2 antihypertensive medications.
A total of 394 patients with a mean systolic blood pressure of 142 mmHg were randomized, and 377 were included in the analysis. In this population, 302 patients were randomized to receive 1 of 4 doses of subcutaneous zilbesiline (150, 300, or 600 mg every 6 months, or 300 mg every 3 months), and 75 patients Take a placebo. The average patient age was 57 years, 56% were male, and approximately 25% were black.
The study was conducted in Canada, Ukraine, the United Kingdom and the United States, with 78% of participants residing in the United States. The investigative team noted that 16 randomly selected patients in Ukraine were excluded from the analysis due to challenges in data collection due to war in the region.
The Phase 2 trial has a 6-month placebo-controlled treatment period, running from July 2021 to June 2023. During the study period, patients who received a single dose of zilebesiline achieved a mean 24-hour systolic blood pressure reduction of ≥10 mmHg compared with patients who received placebo, and blood pressure as well as serum AGT levels were reduced by more than 90% compared with patients who received placebo.
At 3 months of follow-up, patients receiving zilbesilam at doses of 300 mg and 600 mg had a mean reduction in 24-hour mean systolic blood pressure of ≥15 mmHg. After 6 months, individuals who received zilebesiran were significantly more likely to have a mean reduction in 24-hour mean systolic blood pressure of ≥20 mmHg without taking other hypertension medications.
Patients taking zilebesiran were more likely to achieve a 24-hour average systolic blood pressure measurement of ≥130 mmHg at 6 months. Participants across all zilbesilam dose groups consistently experienced significant reductions in daytime and nighttime systolic blood pressure.
In terms of safety, the analysis found a low incidence of adverse events associated with zilbesiline. There were four non-serious related adverse events in the zilbesilan group that led to discontinuation, including two reports of orthostatic hypotension, one report of increased blood pressure, and one report of injection site reaction. No clinically relevant changes in renal or liver function and no adverse effects were observed in the placebo group.
Based on these findings, Bakris noted that quarterly or semiannually administered zilbesiline can effectively and safely lower blood pressure in individuals with uncontrolled hypertension. He noted that a ≥5mmHg reduction in systolic blood pressure was associated with reduced cardiovascular risk.
However, the study was limited to patients with mild to moderate hypertension and a 6-month placebo-controlled period. Bakris and colleagues said future studies will evaluate the long-term safety of zilbesilan and its impact on cardiovascular outcomes.
“These results reinforce zilebesiran’s potential to provide sustained blood pressure control, improve medication compliance through less frequent dosing, and thereby improve outcomes in patients with hypertension,” Bakris said.1
refer to
- A single dose of zilbesiram can safely and effectively lower blood pressure for six months. American Heart Association. November 11, 2023. Accessed 12 November 2023. https://newsroom.heart.org/news/single-dose-of-zilebesiran-safely-and-efficiently-lowered-blood-Pressure-for-six-months.
- Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and Stroke Statistics – 2023 Update: Report from the American Heart Association (A published correction appears in Circulation. 2023 Feb 21;147(8):e622) (A published correction appears in Circulation. 2023 Jul 25;148(4): e4). Loop. 2023;147(8):e93-e621. Number: 10.1161/CIR.0000000000001123