Gouni-Berthold Ioanna
Center for Endocrinology, Diabetes and Preventive Medicine (ZEDP), University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
Atheroscler Suppl. 2017 Nov;30:19-27. doi: 10.1016/j.atherosclerosissup.2017.05.003. Epub 2017 May 31.
Increased triglyceride levels (higher than ∼1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apo-CIII) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. While loss of function mutations in the gene encoding apo-CIII (APOC3) are associated with low triglyceride levels and a decreased risk for cardiovascular disease (CVD), overexpression of APOC3 is associated with hypertriglyceridemia. Although many drugs such as fibrates, statins and omega-3 fatty acids modestly decrease triglyceride levels (and apo-CIII concentrations), there are many patients who still have severe hypertriglyceridemia and are at risk for pancreatitis and potentially CVD. The antisense oligonucleotide (ASO) against APOC3 mRNA volanesorsen (previously called ISIS 304801, ISIS-ApoCIIIRx and IONIS-ApoCIIIRx) robustly decreases both, apo-CIII production and triglyceride concentrations and is being currently evaluated in phase 3 trials. In this narrative review we present the currently available clinical evidence on the efficacy and safety of volanesorsen for the treatment of hypertriglyceridemia.
甘油三酯水平升高（高于约1000mg/dL）与胰腺炎风险增加相关。载脂蛋白CIII（apo-CIII）在甘油三酯和富含甘油三酯的脂蛋白代谢中起关键作用。虽然编码apo-CIII（APOC3）的基因功能丧失突变与低甘油三酯水平及心血管疾病（CVD）风险降低相关，但APOC3的过表达与高甘油三酯血症相关。尽管许多药物如贝特类、他汀类和ω-3脂肪酸可适度降低甘油三酯水平（以及apo-CIII浓度），但仍有许多患者存在严重的高甘油三酯血症，有胰腺炎风险，甚至可能有CVD风险。针对APOC3 mRNA的反义寡核苷酸（ASO）volanesorsen（以前称为ISIS 304801、ISIS-ApoCIIIRx和IONIS-ApoCIIIRx）可显著降低apo-CIII生成和甘油三酯浓度，目前正在进行3期试验评估。在这篇叙述性综述中，我们展示了目前关于volanesorsen治疗高甘油三酯血症疗效和安全性的临床证据。
