Effect of Serial Infusions of CER-001, a Pre-β High-Density Lipoprotein Mimetic, on Coronary Atherosclerosis in Patients Following Acute Coronary Syndromes in the CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial A Randomized Clinical Trial
Effect of Serial Infusions of CER-001, a Pre-β High-Density Lipoprotein Mimetic, on Coronary Atherosclerosis in Patients Following Acute Coronary Syndromes in the CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial A Randomized Clinical Trial
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DOI：
10.1001/jamacardio.2018.2121
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发表时间：
2018-09-01
期刊：
影响因子：
24
通讯作者：
Butters, Julie
中科院分区：
文献类型：
--
作者：
Nicholls, Stephen J.;Andrews, Jordan;Butters, Julie
重要信息CER-001是一种带负电荷的工程化前P高密度脂蛋白（HDL）模拟物，含有载脂蛋白A-I和鞘磷脂。初步研究表明CER-001对胆固醇流出和血管炎症具有良好作用。对先前完成的静脉输注CER-001（3 mg/k）的研究进行的事后再分析显示，通过血管内超声检查评估，静脉输注CER-001可促进高冠状动脉斑块负荷患者的消退。一项多中心试验，通过血管内超声检查，在患有急性冠状动脉综合征（AC 5）和心外膜动脉近段基线动脉粥样硬化体积百分比（PAV）大于30%的患者中，评价每周静脉输注CER-001（3 mg/kg，n = 135）或安慰剂（n = 137）10次的效果。这项研究包括了澳大利亚、匈牙利、荷兰和美国的34家学术和社区医院的ACS患者，这些患者接受了冠状动脉造影。患者于2015年8月15日至2016年11月19日入组。干预参与者随机接受每周CER-001，3 mg/kg，或安慰剂，除他汀类药物外，持续10周。次要疗效指标为标准化总动脉粥样硬化体积的名义变化和斑块消退患者百分比。结果：在293例患者中（平均[SD]年龄，59.8 [9.4]岁; 217例男性[79.8%]和261例白人/种族[96.0%]），86例（29%）在ACS指数之前使用过他汀类药物，272例（918%）在随访时有可评价的影像学。安慰剂组和CER-001组治疗后低密度脂蛋白胆固醇（74 mg/dL vs 79 mg/dL; P = 0.15）和高密度脂蛋白胆固醇（43 mg/dL vs 44 mg/dL;P = 0.66）的中位数水平相似。安慰剂组的主要疗效指标PAV降低0.41%（与基线相比P = 0.005），但CER-001组未降低（-0.09%;与基线相比P = 0.67;组间差异0.32%; P = 0.15）。安慰剂组和CER-001组中PAV消退的患者百分比相似（57.7% vs 53.3%; P = 0.49）。输注的耐受性良好，临床和实验室不良事件之间没有显着差异，观察治疗groups.CONCLUSIONS和RELEVANCE输注CER-001没有促进他汀类药物治疗的ACS和高斑块负荷患者冠状动脉粥样硬化的消退。
IMPORTANCE CER-001 is a negatively charged, engineered pre-P high-density lipoprotein (HDL) mimetic containing apolipoprotein A-I and sphingomyelin. Preliminary studies demonstrated favorable effects of CER-001on cholesterol efflux and vascular inflammation. A post hoc reanalysis of a previously completed study of intravenous infusion of CER-001, 3 mg/k, showed that the intravenous infusion in patients with a high coronary plaque burden promoted regression as assessed by intravascular ultrasonography.OBJECTIVE To determine the effect of infusing CER-001 on coronary atherosclerosis progression in statin-treated patients.DESIGN, SETTING, AND PARTICIPANTS A double-blind, randomized, multicenter trial evaluating the effect of 10 weekly intravenous infusions of CER-001, 3 mg/kg, (n = 135) or placebo (n = 137) in patients with an acute coronary syndrome (AC5) and baseline percent atheroma volume (PAV) greater than 30% in the proximal segment of an epicardial artery by intravascular ultrasonography. The study included 34 academic and community hospitals in Australia, Hungary, the Netherlands, and the United States in patients with ACS presentingfor coronary angiography. Patients were enrolled from August 15, 2015, to November 19, 2016.INTERVENTIONS Participants were randomized to receive weekly CER-001, 3 mg/kg, or placebo for 10 weeks in addition to statins.MAIN OUTCOMES AND MEASURES The primary efficacy measure was the nominal change in PAV from baseline today 78 measured by serial intravascular ultrasonography imaging. The secondary efficacy measures were nominal change in normalized total atheroma volume and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated.RESULTS Among 293 patients (mean [SD] age, 59.8 [9.4] years; 217 men [79.8%] and 261white race/ethnicity [96.0%]), 86 (29%) had statin prior use prior to the index ACS and 272 (918%) had evaluable imaging at follow-up. The placebo and CER-001 groups had similar post treatment median levels of low-density lipoprotein cholesterol (74 mg/dL vs 79 mg/dL; P =.15) and high-density lipoprotein cholesterol (43 mg/dL vs 44mg/dL;P =.66). The primary efficacy measure, PAV, decreased 0.41% with placebo (P =.005 compared with baseline), but not with CER-001 (-0.09%; P =.67 compared with baseline; between group differences, 0.32%; P =.15). Similar percentages of patients in the placebo and CER-001 groups demonstrated regression of PAV (57.7% vs 53.3%; P =.49). Infusions were well tolerated, with no differences in clinical and laboratory adverse events observed between treatment groups.CONCLUSIONS AND RELEVANCE Infusion of CER-001 did not promote regression of coronary atherosclerosis in statin-treated patients with ACS and high plaque burden.