NEJM:心血管疾病患者的脂蛋白(a)降低策略

2020-01-16 xing.T MedSci原创

由此可见,在脂蛋白(a)水平升高并确诊为心血管疾病的患者中,APO(a)-LRx以剂量依赖性方式降低脂蛋白(a)水平。

脂蛋白(a)的水平是由基因决定的,升高时是心血管疾病和主动脉瓣狭窄的危险因素。没有批准的降低脂蛋白(a)水平的治疗药物。近日,顶级医学期刊NEJM上发表了一篇研究文章,研究人员进行了一项随机、双盲、安慰剂对照的剂量变化试验,包含286名已确诊的心血管疾病患者,且脂蛋白(a)水平至少为60 mg/dL(150 nmol/L)。

患者接受肝细胞定向的反义寡核苷酸AKCEA-APO(a)-LRx,在此称为APO(a)-LRx(每4周20、40或60 mg;每2周20 mg;或每周20 mg )或皮下注射盐水安慰剂6到12个月。脂蛋白(a)水平通过不依赖亚型的测定法进行测量。该研究的主要终点是从基线到暴露的第6个月中脂蛋白(a)水平的百分比变化。

六组中的基线脂蛋白(a)的中位数范围为204.5至246.6 nmol/L。APO(a)-LRx的给药导致脂蛋白(a)水平呈剂量依赖性降低,每4周20 mg剂量平均降低35%,每4周40mg降低56%,每2周20mg降低58%,每4周60mg降低72%,每周20mg降低80%,而安慰剂降低6%(与安慰剂比较的P值范围为0.003至<0.001)。在血小板计数、肝和肾指标或流感样症状方面,任何APO(a)-LRx剂量和安慰剂之间无显著差异。最常见的不良事件是注射部位反应。

由此可见,在脂蛋白(a)水平升高并确诊为心血管疾病的患者中,APO(a)-LRx以剂量依赖性方式降低脂蛋白(a)水平。

原始出处:

Sotirios Tsimikas,et al.Lipoprotein(a) Reduction in Persons with Cardiovascular Disease.NEJM.2020.https://www.nejm.org/doi/full/10.1056/NEJMoa1905239

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