Volume 30, Issue 172, June 2026

Zilebesiran in the Treatment of Hypertension: Molecular Insights, Clinical Trial Results, and Future Perspectives

Katarzyna Marcinkowska^1♦, Zofia Leżańska¹, Emil Pałyga¹, Joanna Sowińska¹, Mateusz Kwiatkowski¹, Karolina Siemińska¹, Natalia Paluszkiewicz¹, Sandra Bryg², Aleksandra Cieślak¹, Sara Demkow¹

¹Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland
²Medical University of Silesia in Katowice, Józefa Poniatowskiego 15, 40-055 Katowice, Poland

^♦Corresponding author
Katarzyna Marcinkowska, Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland

ABSTRACT

Introduction: Hypertension is considered the main modifiable risk factor associated with cardiovascular diseases and early death on an international level. Ineffective results are often connected with daily drug intake and poor adherence to drug therapy. Zilebesiran, a novel experimental siRNA, acts by blocking angiotensinogen (AGT) production in the liver. The effect of zilebesiran gives a new approach for blood pressure control. To conduct a review of the zilebesiran drug, its pharmacology, effectiveness, safety, and application prospects in the treatment of hypertension based on clinical trials. Methods: This literature review was conducted via a PubMed search, including clinical trials (Phase I and Phase II), KARDIA-1, KARDIA-2, and KARDIA-3, up to April 2026. Results: Clinical trials show that a single subcutaneous dose of zilebesiran leads to a dose-dependent reduction in serum angiotensinogen (>90%) and a significant, sustained decrease in 24-hour ambulatory systolic blood pressure for up to six months. In studies, KARDIA zilebesiran was effective alone or when co-administered with indapamide and amlodipine. There were adverse effects like mild injection site pain and hyperkalemia. Conclusions: Zilebesiran can help to improve treatment adherenc in patients who have hypertension. The long-term safety profile and the effect on cardiovascular events are still under investigation in larger trials.

Keywords: hypertension; zilebesiran; siRNA; angiotensinogen; RAAS; long-acting agent

Medical Science, 2026, 30, e113ms3917

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DOI: https://doi.org/10.54905/disssi.v30i172.e113ms3917

Published: 29 June 2026