Research Highlights:
Embargoed until 4 p.m. ET, Saturday, Nov. 11, 2023
PHILADELPHIA, Nov. 11, 2023 — A single injection of the experimental medication zilebesiran was safe and effective in reducing systolic blood pressure in people with mild-to-moderate high blood pressure for up to six months, as detailed in the Phase 2 of the KARDIA study, reported as late-breaking science today at the American Heart Association’s Scientific Sessions 2023 . The meeting, Nov. 11-13, in Philadelphia, is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science.
Zilebesiran is an investigational RNA interference agent targeting angiotensinogen (AGT), a hormone produced predominantly in the liver that contributes to blood pressure regulation.
“Uncontrolled high blood pressure is a leading cause of death and disease, so there is a need for new treatments that provide sustained blood pressure control over longer periods of time. This will improve outcomes for people with hypertension,” said lead study author George L. Bakris, M.D., FAHA, a professor of medicine and director of the Comprehensive Hypertension Center at the University of Chicago Medicine. “Uncontrolled hypertension also increases the risk of heart disease.”
According to the American Heart Association’s 2023 Statistical Update , heart disease continues to be the number one cause of death in the United States and nearly half of adults in the U.S. have high blood pressure.
In this global, placebo-controlled, randomized, double-blind trial, researchers investigated the safety and efficacy of administering zilebesiran to people with mild-to-moderate high blood pressure , defined as systolic blood pressure of 135-160 mm Hg, who are untreated or on stable therapy with up to two antihypertensive medications. Systolic blood pressure is the top number in a blood pressure reading and indicates how much pressure blood is exerting against artery walls when the heart contracts.
The 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults classifies stage 1 hypertension as having top and bottom blood pressure measures greater than or equal to 130/80 mm Hg, and stage 2 hypertension as having top and bottom measures greater than or equal to 140/90 mm Hg.
The study included 394 patients with an average systolic blood pressure of 142 mm Hg. Participants were randomized to receive subcutaneous doses of zilebesiran (4 groups: 150, 300 or 600 mg once every six months or 300 mg once every three months) or a placebo.
Over the six-month study period, the analysis found:
In addition, participants in all four zilebesiran groups consistently experienced significantly greater reductions in both daytime and nighttime systolic blood pressure. Low rates of zilebesiran-related adverse events were reported, with the most common being mild reactions at the site of the injection. No clinically relevant changes in kidney or liver function were observed, Bakris noted.
“Our study demonstrates that either quarterly or biannual doses of zilebesiran can effectively and safely lower blood pressure in patients with uncontrolled hypertension,” Bakris said. “It is well known that reductions in systolic blood pressure of greater than or equal to 5 mm Hg are linked to a reduction in cardiovascular risk. These results reinforce the potential of zilebesiran to provide sustained blood pressure control, improve adherence to medication via infrequent dosing, and in turn, improve outcomes for people with high blood pressure.”
Study details and background:
These findings are limited because the KARDIA-1 trial evaluated zilebesiran only in people with mild-to-moderate hypertension. Another study limitation is that results are limited to the six-month placebo-controlled period. Longer-term safety and impact on cardiovascular outcomes will be assessed in future research.
Co-authors, disclosures and funding sources are listed in the abstract.
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