McCullough Peter A, Ballantyne Christie M, Sanganalmath Santosh K, Langslet Gisle, Baum Seth J, Shah Prediman K, Koren Andrew, Mandel Jonas, Davidson Michael H
Baylor University Medical Center, Baylor Heart and Vascular Institute, Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, Texas.
Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas; Center for Cardiovascular Disease Prevention, Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas.
Am J Cardiol. 2018 Apr 15;121(8):940-948. doi: 10.1016/j.amjcard.2017.12.040. Epub 2018 Feb 2.
Patients with previous atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) are at high risk of future cardiovascular events. Despite maximally tolerated doses of statins, many patients still have elevated low-density lipoprotein cholesterol (LDL-C) levels. We evaluated the efficacy and safety of alirocumab in patients with ASCVD and/or HeFH on a maximally tolerated dose of statin (rosuvastatin 20 or 40 mg, atorvastatin 40 or 80 mg, or simvastatin 80 mg, or lower doses with an investigator-approved reason) ± other lipid-lowering therapies from 5 placebo-controlled phase 3 trials (52 to 78 weeks). Patients with (n = 2,449) and without (n = 1,050) ASCVD were pooled from the FH I, FH II, HIGH FH, LONG TERM, and COMBO I trials. Patients with HeFH with (n = 575) and without ASCVD (n = 682) were pooled from all trials except COMBO I. High-intensity statins were utilized in 55.7% to 59.0% and in 72.4% to 87.6% of the ASCVD and the HeFH groups, respectively. Efficacy end points included LDL-C percent change from baseline to week 24 stratified by alirocumab dose. Mean baseline demographics and lipid levels were comparable in alirocumab- and placebo-treated patients. LDL-C reductions from baseline at week 24 ranged from 46.6% to 51.3% for alirocumab 75/150 mg and from 54.1% to 61.9% for alirocumab 150 mg in ASCVD and HeFH groups and were sustained for up to 78 weeks. LDL-C reductions with alirocumab were independent of ASCVD and/or HeFH status (interaction p value >0.05). Concordant results were observed for other lipids analyzed. The overall safety in the subgroups analyzed was similar in both treatment arms. Injection-site reactions were observed more frequently with alirocumab versus placebo.
既往患有动脉粥样硬化性心血管疾病（ASCVD）和/或杂合子家族性高胆固醇血症（HeFH）的患者未来发生心血管事件的风险很高。尽管使用了最大耐受剂量的他汀类药物，但许多患者的低密度脂蛋白胆固醇（LDL-C）水平仍升高。我们在5项安慰剂对照的3期试验（52至78周）中评估了阿利西尤单抗在接受最大耐受剂量他汀类药物（瑞舒伐他汀20或40mg、阿托伐他汀40或80mg、辛伐他汀80mg，或因研究者认可的原因使用更低剂量）±其他降脂疗法的ASCVD和/或HeFH患者中的疗效和安全性。患有ASCVD（n = 2449）和未患有ASCVD（n = 1050）的患者分别来自FH I、FH II、HIGH FH、LONG TERM和COMBO I试验。患有HeFH且患有ASCVD（n = 575）和未患有ASCVD（n = 682）的患者来自除COMBO I试验外的所有试验。高强度他汀类药物在ASCVD组和HeFH组中的使用率分别为55.7%至59.0%和72.4%至87.6%。疗效终点包括按阿利西尤单抗剂量分层的从基线到第24周LDL-C的百分比变化。阿利西尤单抗治疗组和安慰剂治疗组患者的平均基线人口统计学特征和血脂水平具有可比性。在ASCVD和HeFH组中，阿利西尤单抗75/150mg在第24周时LDL-C从基线的降低幅度为46.6%至51.3%，阿利西尤单抗150mg为54.1%至61.9%，且这种降低可持续长达78周。阿利西尤单抗降低LDL-C的效果与ASCVD和/或HeFH状态无关（交互p值>0.05）。对其他分析的血脂也观察到了一致的结果。两个治疗组中分析的亚组的总体安全性相似。与安慰剂相比，阿利西尤单抗更常观察到注射部位反应。
