Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Dec 20;36(4):420-430.
doi: 10.37616/2212-5043.1408. eCollection 2024.

Zilebesiran and Hypertension: A Systematic Review and Meta-analysis

Mohamed Lemine #  1 , Saif Almuzainy #  1 , Rayan Aljubeh  1 , Ahmad Alilo  1
Affiliations
Review

Zilebesiran and Hypertension: A Systematic Review and Meta-analysis

Mohamed Lemine et al. J Saudi Heart Assoc. .

Abstract

Objectives: Zilebesiran is an investigational RNA interference therapeutic designed to lower blood pressure by targeting the hepatic production of angiotensinogen, the most upstream precursor of the renin-angiotensin-aldosterone system. This approach aims to offer long-lasting blood pressure control with potentially fewer doses compared to traditional antihypertensive medications. The objective of this systematic review and meta-analysis was to assess the antihypertensive efficacy of zilebesiran in patients with hypertension.

Methods: We conducted a search across PubMed, Cochrane Library, Ovid, EBSCO, up until July 2024. The eligible studies included randomized controlled trials that examined Zilebesiran versus placebo in hypertensive patients. These studies reported outcomes like reduction in 24-hour systolic blood pressure (SBP) from baseline, changes in plasma angiotensinogen (ATG) levels and office SBP at three months. Meta-analyses were carried out using RevMan.

Results: Our search identified 138 records, of which three randomized controlled trials (RCTs) with 1145 patients met inclusion criteria, focusing on Zilebesiran versus placebo for primary hypertension. Quality assessment revealed two high-quality and one moderate-quality study. Pooled analysis showed Zilebesiran significantly reduced 24-hour systolic blood pressure (SBP) compared to placebo across all doses (MD -12.84, 95% CI -16.00 to -9.68, P < 0.00001), though heterogeneity was high for doses above 500 mg. Zilebesiran also significantly lowered plasma angiotensinogen and office SBP. Sensitivity analysis resolved some heterogeneity issues. Publication bias could not be assessed.

Conclusion: Zilebesiran effectively reduces 24-hour and office systolic blood pressure and plasma angiotensinogen, demonstrating significant antihypertensive benefits. Optimal dosing appears between 250 and 500 mg. Further research should explore patient-specific responses to enhance therapeutic efficacy and minimize side effects.

Keywords: ALN-AGT01; Hypertension; Zilebesiran.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: The authors of this study declare no conflict of interest.

Figures

Fig. 1
Fig. 1
PRISMA study flow diagram.
Fig. 2
Fig. 2
ROB 1 quality assessment of the included studies.
Fig. 3
Fig. 3
Forest plot of pooled mean differences of the mean change from baseline at three months in 24-hour SBP as measured by ABPM for zilebesiran versus placebo.
Fig. 4
Fig. 4
Forest plot of pooled mean differences of the mean change from baseline in plasma ATG in fractions for zilebesiran versus placebo.
Fig. 5
Fig. 5
Forest plot of pooled mean differences of the mean change from baseline at three months in office SBP for zilebesiran versus placebo.
See this image and copyright information in PMC

References

    1. Bromfield S, Muntner P. High blood pressure: the leading global burden of disease risk factor and the need for worldwide prevention programs. Curr Hypertens Rep. 2013;15:134–6. doi: 10.1007/s11906-013-0340-9. - DOI - PMC - PubMed
    1. A global brief on hypertension: silent killer, global public health crisis: World Health Day 2013. n.d. [accessed August 23, 2024]. https://www.who.int/publications/i/item/a-global-brief-on-hypertension-s... .
    1. NCD Risk Factor Collaboration (NCD-RisC) Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021;398:957–80. doi: 10.1016/S0140-6736(21)01330-1. - DOI - PMC - PubMed
    1. Hypertension. n.d. [accessed August 23, 2024]. https://www.who.int/news-room/fact-sheets/detail/hypertension .
    1. Hill MN, Miller NH, Degeest S, Materson BJ, Black HR, et al. American Society of Hypertension Writing Group. Adherence and persistence with taking medication to control high blood pressure. J Am Soc Hypertens. 2011;5:56–63. doi: 10.1016/j.jash.2011.01.001. - DOI - PubMed

LinkOut - more resources