Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy.
Eur J Clin Invest. 2022 Nov;52(11):e13841. doi: 10.1111/eci.13841. Epub 2022 Jul 28.
Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat subjects with sHTG. The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat sHTG. We performed a systematic review and meta-analysis of RCTs on the efficacy and safety of volanesorsen as compared to placebo treatment in patients with severe HTG.
Studies were systematically searched in the PubMed, Web of Science and Scopus databases according to PRISMA guidelines. The last search was performed on 7 February 2022.
Four studies showed significant reduction in TG after 3 months of treatment with volanesorsen as compared with placebo (MD: -73.9%; 95%CI: -93.5%, -54.2; p < .001 I = 89.05%; p < .001); VLDL-C level (MD: -71.0%; 95%CI: -76.6%, -65.4%; p < .001 I = 94.1%; p < .001); Apo-B48 level (MD: -69.03%; 95%CI: -98.59.4%, -39.47%; p < .001, I = 93.51%; p < .001) and Apo-CIII level (MD: -80.0%; 95%CI: -97.5%, -62.5; p < .001 I = 94.1%; p < .001) with an increase in HDL-C level (MD: +45.92%, 95%CI: +37.24%, +54.60%; p < .001 I = 94.34%; p < .001) and in LDL-C level (MD: +68.6%, 95%CI: +7.0%, +130.1%; p < .001 I = 96.18%; p < .001) without a significant elevation of Apo-B100 level (MD: +4.58%, 95%CI: -5.64%, +14.79%; p = .380 I = 95.09%; p < .001) in 139 volanesorsen patients as compared to 100 placebo-treated controls. Most of adverse events were mild and related to local injection site reactions.
In patients with severe HTG, volanesorsen is associated with a significant reduction in TG, VLDL-C, Apo-B48 and non-HDL-C and increment of HDL-C as compared to placebo. Documented efficacy is accompanied by an acceptable safety profile.
严重高甘油三酯血症（sHTG）患者常对降脂治疗产生抵抗。载脂蛋白（Apo）CIII 抑制可能是治疗 sHTG 患者的有前途的方法。针对 APOC3 mRNA 的反义寡核苷酸 volanesorsen 最近被引入用于治疗 sHTG。我们对 RCTs 进行了系统评价和荟萃分析，以评估与安慰剂治疗相比，volanesorsen 在严重 HTG 患者中的疗效和安全性。
根据 PRISMA 指南，在 PubMed、Web of Science 和 Scopus 数据库中系统地搜索了研究。最后一次搜索是在 2022 年 2 月 7 日进行的。
四项研究表明，与安慰剂相比，volanesorsen 治疗 3 个月后 TG 显著降低（MD：-73.9%；95%CI：-93.5%，-54.2%；p<0.001 I²=89.05%；p<0.001）；VLDL-C 水平（MD：-71.0%；95%CI：-76.6%，-65.4%；p<0.001 I²=94.1%；p<0.001）；Apo-B48 水平（MD：-69.03%；95%CI：-98.59.4%，-39.47%；p<0.001，I²=93.51%；p<0.001）和 Apo-CIII 水平（MD：-80.0%；95%CI：-97.5%，-62.5%；p<0.001 I²=94.1%；p<0.001），同时 HDL-C 水平升高（MD：+45.92%；95%CI：+37.24%，+54.60%；p<0.001 I²=94.34%；p<0.001）和 LDL-C 水平升高（MD：+68.6%；95%CI：+7.0%，+130.1%；p<0.001 I²=96.18%；p<0.001），而 Apo-B100 水平无显著升高（MD：+4.58%；95%CI：-5.64%，+14.79%；p=0.380 I²=95.09%；p<0.001）。在 139 名接受 volanesorsen 治疗的患者与 100 名接受安慰剂治疗的对照组相比。大多数不良事件为轻度，与局部注射部位反应有关。
与安慰剂相比，在严重 HTG 患者中，volanesorsen 可显著降低 TG、VLDL-C、Apo-B48 和非 HDL-C，并升高 HDL-C。有记录的疗效伴随着可接受的安全性。
