Stroes Erik, Robinson Jennifer G, Raal Frederick J, Dufour Robert, Sullivan David, Kassahun Helina, Ma Yuhui, Wasserman Scott M, Koren Michael J
Department of Vascular Medicine, Academic Medical Center of Amsterdam, Amsterdam, Netherlands.
Departments of Epidemiology and Medicine, University of Iowa, Iowa City, Iowa.
Clin Cardiol. 2018 Oct;41(10):1328-1335. doi: 10.1002/clc.23049. Epub 2018 Oct 21.
BACKGROUND: Evolocumab significantly lowers low-density lipoprotein cholesterol (LDL-C) when dosed 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) subcutaneously. HYPOTHESIS: LDL-C changes are comparable among different patient subgroups in a pooled analysis of data from phase 3 trials. METHODS: A total of 3146 patients received ≥1 dose of evolocumab or control in four 12-week phase 3 studies. Percent change from baseline in LDL-C for evolocumab 140 mg Q2W or 420 mg QM vs control was reported as the average of week 10 and 12 values. Quantitative and qualitative interactions between treatment group and subgroup by dose regimen were tested. RESULTS: In the pooled analysis, treatment differences vs placebo or ezetimibe were similar for both 140 mg Q2W and 420 mg QM doses across ages (<65 years, ≥65 years); gender; race (Asian, black, white, other); ethnicity (Hispanic, non-Hispanic); region (Europe, North America, Asia Pacific); glucose tolerance status (type 2 diabetes mellitus, metabolic syndrome, neither); National Cholesterol Education Program risk categories (high, moderately high, moderate, low); and European Society of Cardiology/European Atherosclerosis Society risk categories (very high, high, moderate, or low). Certain low-magnitude variations in LDL-C lowering among subgroups led to significant quantitative interaction P values that, when tested by qualitative interaction, were not significant. The incidences of adverse events were similar across groups treated with each evolocumab dosing regimen or control. CONCLUSIONS: Consistent reductions in LDL-C were observed in the evolocumab group regardless of demographic and disease characteristics.
背景:每2周皮下注射140mg(Q2W)或每月皮下注射420mg(QM)的依洛尤单抗可显著降低低密度脂蛋白胆固醇(LDL-C)水平。 假设:在3期试验数据的汇总分析中,不同患者亚组的LDL-C变化具有可比性。 方法:在四项为期12周的3期研究中,共有3146例患者接受了≥1剂依洛尤单抗或对照治疗。依洛尤单抗140mg Q2W或420mg QM与对照相比,LDL-C自基线的百分比变化报告为第10周和第12周数值的平均值。对治疗组和剂量方案亚组之间的定量和定性相互作用进行了测试。 结果:在汇总分析中,140mg Q2W和420mg QM剂量组与安慰剂或依折麦布相比,在各年龄组(<65岁、≥65岁)、性别、种族(亚洲、黑人、白人、其他)、族裔(西班牙裔、非西班牙裔)、地区(欧洲、北美、亚太地区)、糖耐量状态(2型糖尿病、代谢综合征、均无)、美国国家胆固醇教育计划风险类别(高、中度高、中度、低)以及欧洲心脏病学会/欧洲动脉粥样硬化学会风险类别(极高、高、中度或低)中的治疗差异相似。亚组间LDL-C降低幅度存在一定程度的微小差异,导致定量相互作用P值具有显著性,但经定性相互作用检验后并不显著。各依洛尤单抗给药方案组或对照组的不良事件发生率相似。 结论:无论人口统计学和疾病特征如何,依洛尤单抗组均观察到LDL-C持续降低。
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