对于严重的高甘油三血症而言,Plozasiran (ARO-APOC3):SHASTA-2随机临床试验
Daniel Gaudet1, Denes Pall2, Gerald F Watts3
1ECOGENE-21 QC, Department of Medicine, Université de Montréal, Montréal, Quebec, Canada.
JAMA cardiology
|April 7, 2024
概括
在患有严重高甘油三血症 (sHTG) 的患者中,Plozasiran有效降低了甘油三和阿波利波蛋白C3水平. 大多数参与者达到低于急性胰腺炎风险值的甘油三水平,具有有利的安全性.
科学领域:
- 心血管医学 心血管医学
- 药理学 药理学是指药理学的学科.
- 遗传学 是一个遗传学.
背景情况:
- 严重的高甘油三血症 (sHTG) 显著增加了动脉样硬化心血管疾病 (ASCVD),非酒精性脂肪肝炎和急性胰腺炎的风险.
- 尽管有当前的治疗方法,但与sHTG相关的发病率仍然存在,这凸显了对新型治疗策略的需求.
研究的目的:
- 评估小干扰RNA (siRNA) 向APOC3的plozasiran的耐受性,疗效和最佳剂量,用于管理sHTG.
- 评估普洛萨西兰对三甘水平,阿波利波蛋白C3 (APOC3) 降低和其他脂质参数的影响.
主要方法:
- SHASTA-2试验是一项2b期,安慰剂控制,双盲,随机临床试验,涉及患有sHTG的成年人.
- 参与者在12周内两次接受皮下剂量的plozasiran (10,25或50毫克) 或安慰剂,随访时间为48周.
- 主要终点是24周甘油三水平中果减去的平均百分比变化,使用混合模型重复测量进行分析.
主要成果:
- 在第24周,Plozasiran表现出显著的,剂量依赖的甘油三水平 (高达-57%) 和APOC3水平 (高达-77%) 的显著降低.
- 在用普洛萨西兰治疗的患者中,有91%的患者达到了低于500mg/dL的甘油三水平.
- 虽然LDL-C因剂量而增加,但ApoB水平保持稳定,非HDL-C和残留胆固醇下降;安全性概况是有利的,副作用的发生率与安慰剂相似.
结论:
- 普洛萨西兰有效降低sHTG患者的甘油三水平,大多数患者达到急性胰腺炎风险值以下的水平.
- 该药物在与甘油三相关的脂蛋白和一般有利的安全性方面有所改善,尽管LDL-C增加了.
- 需要进一步的研究来证实plozasiran的长期益处及其对sHTG相关临床结果的影响.
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