Reimagining Blood Pressure Management: The Role of Zilebesiran in Targeting Angiotensinogen

Hypertension remains a major global health burden and a leading risk factor for cardiovascular morbidity and mortality. Despite the availability of multiple antihypertensive therapies, a significant proportion of patients fail to achieve optimal BP control due to limited efficacy, side effects, or poor adherence. Zilebesiran (siRNA)-based therapy is a novel drug emerging for the hypertension control. This drug targets hepatic angiotensinogen synthesis and lowers blood pressure for a prolonged time compared to traditional antihypertensive medications. This review analyses current clinical trial data on Zilebesiran, with a focus on its efficacy and safety profile in hypertensive patients. A comprehensive literature search was conducted across PubMed, Embase, ClinicalTrials.gov, and Cochrane Library through June 2025, identifying phase I-II randomized controlled trials. The studies show Zilebesiran is efficient in significant and sustained reductions in 24-hour ambulatory SBP, with effects lasting up to six months following a single subcutaneous dose. The treatment was well-tolerated, with the most common adverse events being mild injection site reactions. Zilebesiran represents a promising new approach for hypertension management, offering long-acting BP control and potential benefits in patients with adherence challenges. However, further large-scale trials are essential to establish long-term safety and cardiovascular outcomes in broader and higher-risk populations.