Background:Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain.Methods:The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models.Results:Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5], and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata <75, 75–<90, ≥90 mg/dL, respectively; P_trend<0.0001) and after adjustment for low-density lipoprotein cholesterol (P_trend=0.035). Higher baseline apoB stratum was associated with greater relative (P_trend<0.0001) and absolute reduction in MACE with alirocumab versus placebo. In the alirocumab group, the incidence of MACE after month 4 decreased monotonically across decreasing achieved apoB strata (4.26 [95% CI, 3.78–4.79], 3.09 [95% CI, 2.69–3.54], and 2.41 [95% CI, 2.11–2.76] events per 100 patient-years in strata ≥50, >35–<50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol but not vice versa.Conclusions:In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01663402.

中文翻译：

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载脂蛋白 B、急性冠状动脉综合征后的残余心血管风险和 Alirocumab 的影响

背景：载脂蛋白 B (apoB) 提供了动脉粥样硬化风险的综合衡量标准。除低密度脂蛋白胆固醇提供的信息外，apoB 水平和 apoB 降低是否持有关于急性冠脉综合征后残余风险的增量预测信息尚不确定。比较了前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型抑制剂 alirocumab 与安慰剂在 18 924 名近期患有急性冠状动脉综合征和尽管优化了他汀类药物治疗但致动脉粥样化脂蛋白升高的患者中的效果。主要结局是主要不良心血管事件（MACE；冠心病死亡、非致死性心肌梗死、致死性/非致死性缺血性卒中、因不稳定型心绞痛住院）。在调整后的 Cox 比例风险和倾向评分匹配模型中评估基线 apoB 或 4 个月时的 apoB 与 MACE 之间的关联。结果：中位随访时间为 2.8 年。在安慰剂组的比例风险分析中，随着基线 apoB 层的增加，MACE 发生率增加（3.2 [95% CI，2.9-3.6]、4.0 [95% CI，3.6-4.5] 和 5.5 [95% CI，5.0-6.1） ] 分层中每 100 患者年的事件分别为 <75、75–<90、≥90 mg/dL；P_趋势<0.0001) 和调整低密度脂蛋白胆固醇后 ( P_趋势=0.035)。较高的基线 apoB 层与较大的相关（P_趋势<0.0001) 和 alirocumab 与安慰剂相比 MACE 的绝对减少。在 alirocumab 组中，第 4 个月后 MACE 的发生率在降低实现的 apoB 层中单调下降（4.26 [95% CI，3.78-4.79]、3.09 [95% CI，2.69-3.54] 和 2.41 [95% CI，2.11） –2.76] 每 100 患者年的事件发生率分别为 ≥50、>35–<50 和 ≤35 mg/dL）。与来自安慰剂组的倾向评分匹配患者相比，alirocumab 的治疗风险比在实现的 apoB 层中也单调下降。达到的 apoB 可预测在调整达到的低密度脂蛋白胆固醇或非高密度脂蛋白胆固醇后的 MACE，但反之亦然。结论：在近期患有急性冠状动脉综合征和致动脉粥样化脂蛋白升高的患者中，MACE 在基线 apoB 层中增加。Alirocumab 减少了基线 apoB 所有层的 MACE，基线水平较高的患者的绝对减少幅度更大。较低的实现 apoB 与较低的 MACE 风险相关，即使在考虑了实现的低密度脂蛋白胆固醇或非高密度脂蛋白胆固醇之后，这表明 apoB 提供了增量信息。实现低至 ≤35 mg/dL 的 apoB 水平可降低急性冠脉综合征后脂蛋白归因的残余风险。注册：URL：https://www.clinicaltrials.gov；唯一标识符：NCT01663402。即使考虑到已达到的低密度脂蛋白胆固醇或非高密度脂蛋白胆固醇，这表明 apoB 提供了增量信息。实现低至 ≤35 mg/dL 的 apoB 水平可降低急性冠脉综合征后脂蛋白归因的残余风险。注册：URL：https://www.clinicaltrials.gov；唯一标识符：NCT01663402。即使考虑到已达到的低密度脂蛋白胆固醇或非高密度脂蛋白胆固醇，这表明 apoB 提供了增量信息。实现低至 ≤35 mg/dL 的 apoB 水平可降低急性冠脉综合征后脂蛋白归因的残余风险。注册：URL：https://www.clinicaltrials.gov；唯一标识符：NCT01663402。