University of Iowa, Iowa City, Iowa.
Icahn School of Medicine at Mount Sinai, New York, New York.
J Am Coll Cardiol. 2017 Feb 7;69(5):471-482. doi: 10.1016/j.jacc.2016.11.037.
Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies can reduce low-density lipoprotein cholesterol (LDL-C) to very low levels when added to background lipid-lowering therapy.
The safety of alirocumab was evaluated in patients with at least 2 consecutive LDL-C values <25 or <15 mg/dl in the ODYSSEY program, with follow-up as long as 104 weeks.
Pooled data from 14 trials were analyzed (double-blind treatment 8 to 104 weeks; n = 3,340 alirocumab, n = 1,894 control [placebo or ezetimibe]; representing 4,029 [alirocumab] and 2,114 [control] double-blind patient-years' exposure).
In alirocumab-treated patients, 839 (25.1%) achieved 2 consecutive LDL-C values <25 mg/dl, and 314 (9.4%) achieved <15 mg/dl. Baseline LDL-C was lower (mean 100.3 vs. 134.3 mg/dl) in patients with LDL-C <25 versus ≥25 mg/dl. Similar rates of adverse events occurred in patients achieving LDL-C <25 and <15 mg/dl (72.7% and 71.7%, respectively), compared with 76.6% in those who did not achieve LDL-C <25 mg/dl. Neurological and neurocognitive events were similar among the 3 groups. In a propensity score analysis, the rate of cataracts was higher in patients with LDL-C <25 mg/dl (2.6%) versus ≥25 mg/dl (0.8%; hazard ratio: 3.40; 95% confidence interval: 1.58 to 7.35). However, no difference in cataract incidence was observed between pooled alirocumab and control groups.
LDL-C levels <25 or <15 mg/dl on alirocumab were not associated with an increase in overall treatment-emergent adverse event rates or neurocognitive events, although cataract incidence appeared to be increased in the group achieving LDL-C levels <25 mg/dl. (Pooled analyses of already reported trials; NCT01288443, NCT01288469, NCT01266876, NCT01812707, NCT01507831, NCT01617655, NCT01623115, NCT01709500, NCT01644175, NCT01644188, NCT01730040, NCT01730053, NCT01644474, and NCT01709513).
在 ODYSSEY 项目中，当添加到背景降脂治疗中时，前蛋白转化酶枯草溶菌素/克氏蛋白酶 9 单克隆抗体可将低密度脂蛋白胆固醇（LDL-C）降低到非常低的水平。
评估在 ODYSSEY 项目中至少有 2 次 LDL-C 值<25 或 <15mg/dl 的患者中阿利西尤单抗的安全性，随访时间最长为 104 周。
对来自 14 项试验的汇总数据进行分析（双盲治疗 8 至 104 周；n=3340 例阿利西尤单抗，n=1894 例对照[安慰剂或依折麦布]；分别代表 4029[阿利西尤单抗]和 2114[对照]双盲患者年暴露）。
在阿利西尤单抗治疗的患者中，839 例（25.1%）连续 2 次 LDL-C 值<25mg/dl，314 例（9.4%）<15mg/dl。LDL-C 基线值较低（平均 100.3 vs. 134.3mg/dl），LDL-C<25mg/dl 的患者与 LDL-C≥25mg/dl 的患者相比。在达到 LDL-C<25 和<15mg/dl 的患者中，不良事件的发生率相似（分别为 72.7%和 71.7%），而未达到 LDL-C<25mg/dl 的患者为 76.6%。3 组之间的神经和神经认知事件相似。在倾向评分分析中，LDL-C<25mg/dl 的患者白内障发生率高于 LDL-C≥25mg/dl 的患者（2.6%比 0.8%；危险比：3.40；95%置信区间：1.58 至 7.35）。然而，在阿利西尤单抗和对照组之间未观察到白内障发生率的差异。
阿利西尤单抗治疗后 LDL-C 水平<25 或<15mg/dl 与总治疗突发不良事件率或神经认知事件的增加无关，尽管在 LDL-C 水平<25mg/dl 的组中，白内障的发生率似乎有所增加。（已报告试验的汇总分析；NCT01288443、NCT01288469、NCT01266876、NCT01812707、NCT01507831、NCT01617655、NCT01623115、NCT01709500、NCT01644175、NCT01644188、NCT01730040、NCT01730053、NCT01644474 和 NCT01709513）。
