Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies
Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies
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DOI：
10.1186/s12933-019-0951-9
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发表时间：
2019-11-09
影响因子：
9.3
通讯作者：
Leiter, Lawrence A.
中科院分区：
文献类型：
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作者：
Ray, Kausik K.;Del Prato, Stefano;Leiter, Lawrence A.
背景糖尿病患者常伴有高水平的致动脉粥样硬化脂蛋白和胆固醇，表现为低密度脂蛋白胆固醇（LDL-C）、非高密度脂蛋白胆固醇（non-HDL-C）、载脂蛋白B（ApoB）和低密度脂蛋白颗粒数（LDL-PN）升高。动脉粥样硬化性心血管疾病（ASCVD）的存在增加了未来心血管事件的风险。我们评估了前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK 9）抑制剂alirocumab在2型糖尿病（T2 DM）、高LDL-C或非HDL-C患者中的疗效和安全性，并在ODYSSEY DM-血脂异常患者中接受最大耐受他汀类药物治疗的确诊ASCVD患者中进行了研究。（NCT 02642159）和DM-胰岛素方法在DM-血脂异常中，T2 DM和混合性血脂异常个体（非HDL-C>= 100 mg/dL; n=413）随机分配至开放标签alirocumab 75 mg每2周一次（Q2 W）或常规护理（UC），持续24周，在分层随机化前选择UC选项。在DM-INSULIN中，胰岛素治疗的T2 DM（LDL-C >= 70 mg/dL; n=441）个体以双盲方式随机接受alirocumab 75 mg Q2 W或安慰剂治疗24周。研究参与者的糖化血红蛋白也≥ 100 mg/dL（DM-血脂异常）。从这些study.ResultsThis分析包括142 DM-血脂异常和177 DM-胰岛素参与者ASCVD，包括95.1%和86.4%的冠心病，32.4%和49.7%的微血管糖尿病并发症，分别与ASCVD患者的血脂降低和安全性进行了评估。第24周时，与对照组相比，alirocumab使LDL-C、非HDL-C、ApoB和LDL-PN较基线显著降低。这意味着达到非HDL-C的个体比例更高
BackgroundIndividuals with diabetes often have high levels of atherogenic lipoproteins and cholesterol reflected by elevated low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and LDL particle number (LDL-PN). The presence of atherosclerotic cardiovascular disease (ASCVD) increases the risk of future cardiovascular events. We evaluated the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, among individuals with type 2 diabetes (T2DM), high LDL-C or non-HDL-C, and established ASCVD receiving maximally tolerated statin in ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) and DM-INSULIN (NCT02585778).MethodsIn DM-DYSLIPIDEMIA, individuals with T2DM and mixed dyslipidemia (non-HDL-C >= 100 mg/dL; n=413) were randomized to open-label alirocumab 75 mg every 2 weeks (Q2W) or usual care (UC) for 24 weeks, with UC options selected before stratified randomization. In DM-INSULIN, insulin-treated individuals with T2DM (LDL-C >= 70 mg/dL; n=441) were randomized in a double-blind fashion to alirocumab 75 mg Q2W or placebo for 24 weeks. Study participants also had a glycated hemoglobin= 100 mg/dL (DM-DYSLIPIDEMIA). Lipid reductions and safety were assessed in patients with ASCVD from these studies.ResultsThis analysis included 142 DM-DYSLIPIDEMIA and 177 DM-INSULIN participants with ASCVD, including 95.1% and 86.4% with coronary heart disease, and 32.4% and 49.7% with microvascular diabetes complications, respectively. At week 24, alirocumab significantly reduced LDL-C, non-HDL-C, ApoB, and LDL-PN from baseline versus control. This translated into a greater proportion of individuals achieving non-HDL-C