Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA.
State University of New York, Downstate School of Public Health, Brooklyn, New York, USA; CPC Clinical Research and Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA.
J Am Coll Cardiol. 2021 Aug 3;78(5):421-433. doi: 10.1016/j.jacc.2021.04.102.
Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk.
In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels.
ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL).
In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (P = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with P = 0.43.
In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).
指南建议，如果低密度脂蛋白胆固醇（LDL-C）在最大耐受他汀类药物治疗后仍≥70mg/dL，则对有发生重大不良心血管事件（MACE）极高风险的患者使用非他汀类降脂药。目前尚不确定这种方法是否对 LDL-C 接近 70mg/dL 的患者有益。脂蛋白（a）水平可能会影响残余风险。
在 ODYSSEY 结局（急性冠状动脉综合征治疗期间评估心血管结局后用依洛尤单抗）试验的事后分析中，作者评估了在 LDL-C 水平接近 70mg/dL 的患者中，添加前蛋白转化酶枯草溶菌素 9 抑制剂依洛尤单抗来优化他汀类药物治疗的获益。根据同时存在的脂蛋白（a）水平评估了疗效。
ODYSSEY 结局比较了依洛尤单抗与安慰剂在 18924 例接受优化他汀类药物治疗的近期急性冠状动脉综合征患者中的疗效。在 4351 例（23.0%）患者中，筛查或随机 LDL-C＜70mg/dL（中位数 69.4mg/dL；四分位距 64.3-74.0mg/dL）；在 14573 例（77.0%）患者中，两次测定均≥70mg/dL（中位数 94.0mg/dL；四分位距 83.2-111.0mg/dL）。
在 LDL-C 较低的亚组中，安慰剂治疗的患者基线脂蛋白（a）大于或等于中位数（13.7mg/dL）时，MACE 发生率分别为每 100 患者年 4.2 和 3.1。相应的调整后治疗风险比分别为 0.68（95%置信区间[CI]：0.52-0.90）和 1.11（95%CI：0.83-1.49），MACE 治疗-脂蛋白（a）交互作用的 P 值为 0.017。在 LDL-C 较高的亚组中，安慰剂治疗的患者脂蛋白（a）＞13.7mg/dL 或≤13.7mg/dL 时，MACE 发生率分别为每 100 患者年 4.7 和 3.8；相应的调整后治疗风险比分别为 0.82（95%CI：0.72-0.92）和 0.89（95%CI：0.75-1.06），P 值为 0.43。
在近期发生急性冠状动脉综合征且 LDL-C 在接受优化他汀类药物治疗后接近 70mg/dL 的患者中，前蛋白转化酶枯草溶菌素 9 抑制剂的抑制作用仅在脂蛋白（a）浓度至少轻度升高时才提供额外的临床获益。（ODYSSEY 结局：急性冠状动脉综合征治疗期间用依洛尤单抗评估心血管结局；NCT01663402）。
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