Lemine Mohamed, Almuzainy Saif, Aljubeh Rayan, Alilo Ahmad
College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
J Saudi Heart Assoc. 2024 Dec 20;36(4):420-430. doi: 10.37616/2212-5043.1408. eCollection 2024.
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.
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.
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.
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.
Zilebesiran是一种处于研究阶段的RNA干扰疗法，旨在通过靶向肝脏中血管紧张素原（肾素-血管紧张素-醛固酮系统最上游的前体）的生成来降低血压。与传统抗高血压药物相比，这种方法旨在以可能更少的剂量实现持久的血压控制。本系统评价和荟萃分析的目的是评估Zilebesiran在高血压患者中的降压疗效。
我们检索了截至2024年7月的PubMed、Cochrane图书馆、Ovid、EBSCO。符合条件的研究包括在高血压患者中比较Zilebesiran与安慰剂的随机对照试验。这些研究报告了从基线开始24小时收缩压（SBP）的降低、血浆血管紧张素原（ATG）水平的变化以及三个月时的诊室SBP等结果。使用RevMan进行荟萃分析。
我们的检索共识别出138条记录，其中三项包含1145例患者的随机对照试验（RCT）符合纳入标准，重点是Zilebesiran与安慰剂用于原发性高血压的比较。质量评估显示两项高质量研究和一项中等质量研究。汇总分析表明，与安慰剂相比，Zilebesiran在所有剂量下均显著降低24小时收缩压（SBP）（MD -12.84，95%CI -16.00至-9.68，P < 0.00001），尽管500 mg以上剂量的异质性较高。Zilebesiran还显著降低了血浆血管紧张素原和诊室SBP。敏感性分析解决了一些异质性问题。无法评估发表偏倚。
Zilebesiran可有效降低24小时和诊室收缩压以及血浆血管紧张素原，显示出显著的降压益处。最佳剂量似乎在250至500 mg之间。进一步的研究应探索患者的特异性反应，以提高治疗效果并尽量减少副作用。
