Montreal Heart Institute Research Center, Montreal Heart Institute, Montreal, Canada.
Faculty of Medicine, Université de Montréal, Montreal, Canada.
Expert Opin Investig Drugs. 2019 Dec;28(12):1059-1079. doi: 10.1080/13543784.2019.1696772.
: Elevated triglyceride (TG) level is a prevalent condition in the general population and in patients with cardiovascular (CV) risk even under statin therapy. Severe hypertriglyceridemia (HTG) puts patients at risk for acute pancreatitis. Several TG-lowering drugs failed in clinical trials, but subgroup analyses suggest that high-risk patients, such as those with atherogenic dyslipidemia or diabetes, benefit from TG lowering.: We review advances for TG-lowering drugs in clinical development. These include selective PPARα modulators, omega-3 fatty acid formulations that have been approved for severe HTG, and inhibitors of apolipoprotein C-III, angiopoietin-like-3 or microsomal transfer protein. Lessons learned from the success of the phase 3 trial REDUCE-IT with high-dose icosapent ethyl are also reviewed.: We believe that TG-lowering therapies are coming of age as they will allow to treat patients with high CV risk and moderate HTG, including T2D subjects, as well as patients with severe HTG or even homozygous familial hypercholesterolemia, all of which being 'optimally' treated with a statin. More studies on the impact of therapy on quality of life in patients with severe HTG should be conducted with the help of patient registries.
甘油三酯（TG）水平升高在普通人群和心血管（CV）风险患者中很常见，即使在他汀类药物治疗下也是如此。严重的高甘油三酯血症（HTG）使患者面临急性胰腺炎的风险。几种降低 TG 的药物在临床试验中失败，但亚组分析表明，高危患者，如具有动脉粥样硬化性血脂异常或糖尿病的患者，从降低 TG 中获益。
我们回顾了临床开发中用于降低 TG 的药物的进展。这些药物包括选择性过氧化物酶体增殖物激活受体-α调节剂、已批准用于严重 HTG 的ω-3 脂肪酸制剂，以及载脂蛋白 C-III、血管生成素样-3 或微粒体转移蛋白抑制剂。还回顾了高剂量依泽替米贝的 3 期 REDUCE-IT 试验成功的经验教训。
我们认为，降低 TG 的治疗方法正在兴起，因为它们将使具有高心血管风险和中度 HTG 的患者（包括 2 型糖尿病患者）以及严重 HTG 甚至纯合子家族性高胆固醇血症患者受益，所有这些患者都可以通过他汀类药物“最佳”治疗。应借助患者登记处，开展更多关于治疗对严重 HTG 患者生活质量影响的研究。
