Advancing hypertension management: the role of zilebesiran as an siRNA therapeutic agent.

Abstract

Elevated blood pressure poses a significant global health challenge, affecting over 1.28 billion adults worldwide, with a staggering 46% unaware of their condition. Despite its pervasive impact and association with cardiovascular disease, hypertension remains inadequately controlled, highlighting the urgent need for innovative treatment approaches. This review explores the potential of small interfering RNA (siRNA) therapeutics, focusing on zilebesiran, as a promising strategy for hypertension management. SiRNA therapy represents a groundbreaking approach to selectively modulate protein production, offering targeted intervention in the pathophysiological mechanisms underlying hypertension. Zilebesiran, a siRNA, targets hepatic angiotensinogen (AGT) synthesis through interaction with the asialoglycoprotein receptor, ultimately reducing angiotensin II levels and reducing blood pressure. Zilebesiran demonstrates remarkable pharmacokinetic properties, with sustained efficacy observed after single-dose administration. Clinical trials evaluating zilebesiran have shown significant reductions in blood pressure, with effects lasting up to 24 weeks post-administration. Moreover, combination therapy with angiotensin receptor blockers has demonstrated enhanced efficacy, highlighting the potential for synergistic effects in hypertension management. Importantly, zilebesiran exhibits a favorable safety profile, with manageable adverse events, primarily injection site reactions. Zilebesiran represents a transformative therapy in hypertension management, offering targeted and potent blood pressure reduction with favorable safety and dosing characteristics. Its emergence highlights the ongoing evolution of cardiovascular pharmacology and underscores the importance of innovative approaches to address the global burden of hypertension. Moving forward, concerted efforts in research and clinical practice are necessary to realize the benefits of zilebesiran into hypertension management protocols, ultimately advancing cardiovascular health worldwide.