BACKGROUND AND AIMS In the AEGIS-II trial (NCT03473223), CSL112, a human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity, did not significantly reduce the risk of the primary endpoint through 90 days vs. placebo after acute myocardial infarction (MI). Nevertheless, given the well-established relationship between higher low-density lipoprotein cholesterol (LDL-C) and plaque burden, as well as greater risk reductions seen with PCSK9 inhibitors in patients with baseline LDL-C ≥ 100 mg/dL on statin therapy, the efficacy of CSL112 may be influenced by baseline LDL-C. METHODS Overall, 18 219 patients with acute MI, multivessel coronary artery disease, and additional risk factors were randomized to either four weekly infusions of 6 g CSL112 or placebo. This exploratory post-hoc analysis evaluated cardiovascular outcomes by baseline LDL-C in patients prescribed guideline-directed statin therapy at the time of randomization (n = 15 731). RESULTS As baseline LDL-C increased, the risk of the primary endpoint at 90 days lowered in those treated with CSL112 compared with placebo. In patients with LDL-C ≥ 100 mg/dL at randomization, there was a significant risk reduction of cardiovascular death, MI, or stroke in the CSL112 vs. placebo group at 90, 180, and 365 days [hazard ratio .69 (.53-.90), .71 (.57-.88), and .78 (.65-.93)]. In contrast, there was no difference between treatment groups among those with LDL-C < 100 mg/dL at baseline. CONCLUSIONS In this population, treatment with CSL112 compared to placebo was associated with a significantly lower risk of recurrent cardiovascular events among patients with a baseline LDL-C ≥ 100 mg/dL. Further studies need to confirm that CSL112 efficacy is influenced by baseline LDL-C.

中文翻译：

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根据基线 LDL-胆固醇水平，载脂蛋白 A-I 输注和急性心肌梗死的心血管结局：AEGIS-II 试验。


背景和目的在 AEGIS-II 试验 （NCT03473223） 中，CSL112 是一种源自血浆的人载脂蛋白 A1，可增加胆固醇外排能力，与安慰剂相比，在急性心肌梗死 （MI） 后 90 天内未显著降低主要终点的风险。然而，鉴于较高的低密度脂蛋白胆固醇 （LDL-C） 与斑块负荷之间的明确关系，以及在他汀类药物治疗的基线 LDL-C ≥ 100 mg/dL 患者中，PCSK9 抑制剂的风险降低幅度更大，CSL112 的疗效可能受基线 LDL-C 的影响。方法 总体而言，18 219 例急性心肌梗死、多支冠状动脉疾病和其他危险因素患者被随机分配至每周 4 次输注 6 g CSL112 或安慰剂组。这项探索性事后分析通过基线 LDL-C 评估了在随机分组时接受指南指导的他汀类药物治疗的患者的心血管结局 （n = 15 731）。结果随着基线 LDL-C 的增加，与安慰剂相比，CSL112 治疗组患者在 90 天时达到主要终点的风险降低。在随机分组时 LDL-C ≥ 100 mg/dL 的患者中，与安慰剂组相比，CSL112 在 90、180 和 365 天时心血管死亡、心肌梗死或中风的风险显著降低 [风险比 .69 （.53-.90）、.71 （.57-.88） 和 .78 （.65-.93）]。相比之下，基线时 LDL-C < 100 mg/dL 的患者在治疗组间没有差异。结论在该人群中，与安慰剂相比，CSL112 治疗与基线 LDL-C ≥ 100 mg/dL 的患者心血管事件复发风险显着降低相关。进一步的研究需要证实 CSL112 疗效受基线 LDL-C 的影响。