Groupe Hospitalier Pitié-Salpêtrière, Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardiovasculaires, Paris, France.
The Christ Hospital, Heart and Vascular Center/The Lindner Research Center, Cincinnati, Ohio, USA.
J Clin Lipidol. 2019 May-Jun;13(3):443-454. doi: 10.1016/j.jacl.2019.04.005. Epub 2019 Apr 10.
Patients with prior cardiovascular events are at very high risk of recurrent events and may benefit from low-density lipoprotein cholesterol (LDL-C) lowering beyond that achieved with maximally tolerated statins.
To assess potential differences between the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor, alirocumab, in patients with vs without prior myocardial infarction (MI)/ischemic stroke.
Data (n = 4880) were pooled from nine ODYSSEY phase 3 trials of alirocumab 75/150 mg or 150 mg every 2 weeks, mostly on background statins ± other lipid-lowering therapies. Analyses were performed according to statin status, alirocumab dose, and control (placebo or ezetimibe).
Baseline LDL-C, non-high-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B levels were lower and lipoprotein(a) higher in patients with than without prior MI/ischemic stroke. LDL-C levels were reduced from baseline to week 24 in patients with (51.1%-62.9%) and without (43.6%-58.3%) prior MI/ischemic stroke, with no significant interaction between prior MI/ischemic stroke status and LDL-C-lowering efficacy of alirocumab vs controls. Alirocumab significantly reduced other lipid/lipoproteins (including lipoprotein[a]) similarly in patients with/without MI/ischemic stroke. Week 24 LDL-C goal attainment rates for subgroups with/without prior MI/ischemic stroke on background statins were 74.1%-84.8% and 63.7%-74.7%, respectively. The safety profile of alirocumab was generally similar regardless of prior MI/ischemic stroke status.
Alirocumab significantly reduced LDL-C and other atherogenic lipids/lipoproteins in patients with prior MI/ischemic stroke, and the majority of this very high cardiovascular risk population achieved LDL-C goals; efficacy and safety results were similar in patients without prior MI/ischemic stroke.
有过心血管事件的患者复发风险极高，可能会受益于低密度脂蛋白胆固醇（LDL-C）的降低，超过最大耐受他汀类药物所能达到的水平。
评估前心肌梗死（MI）/缺血性脑卒中患者与无此类病史患者中，前蛋白转化酶枯草溶菌素/糜蛋白酶 9 抑制剂阿利西尤单抗的疗效和安全性差异。
汇总了 9 项阿利西尤单抗 75/150mg 或每 2 周 150mg 的 ODYSSEY 阶段 3 试验数据（n=4880），主要在他汀类药物的基础上加用或不加用其他降脂疗法。分析按照他汀类药物状态、阿利西尤单抗剂量和对照（安慰剂或依折麦布）进行。
与无 MI/缺血性脑卒中病史的患者相比，有此类病史的患者基线时 LDL-C、非高密度脂蛋白胆固醇、高密度脂蛋白胆固醇和载脂蛋白 B 水平更低，脂蛋白（a）更高。有 MI/缺血性脑卒中病史的患者（51.1%-62.9%）和无 MI/缺血性脑卒中病史的患者（43.6%-58.3%）在 24 周时 LDL-C 水平均较基线降低，阿利西尤单抗与对照组相比 LDL-C 降低疗效在有/无 MI/缺血性脑卒中病史的患者中无显著交互作用。阿利西尤单抗也可显著降低其他血脂/脂蛋白（包括脂蛋白（a））。有/无 MI/缺血性脑卒中病史的患者在他汀类药物背景治疗下，第 24 周 LDL-C 目标达标率分别为 74.1%-84.8%和 63.7%-74.7%。阿利西尤单抗的安全性特征总体上与 MI/缺血性脑卒中病史状态无关。
阿利西尤单抗可显著降低有 MI/缺血性脑卒中病史患者的 LDL-C 和其他致动脉粥样硬化血脂/脂蛋白，该极高心血管风险人群的大多数患者达到了 LDL-C 目标；无 MI/缺血性脑卒中病史患者的疗效和安全性结果相似。
