Imperial Centre for Cardiovascular Disease Prevention, Imperial College London, London, UK.
Imperial Centre for Cardiovascular Disease Prevention, Imperial College London, London, UK.
Atherosclerosis. 2019 Sep;288:85-93. doi: 10.1016/j.atherosclerosis.2019.07.008. Epub 2019 Jul 12.
Guidelines recommend high-intensity statins for patients with atherosclerotic cardiovascular disease (ASCVD). Subgroups with comorbidities that increase cardiovascular risk, such as diabetes mellitus (DM), chronic kidney disease (CKD) or polyvascular disease (PoVD), may derive greater absolute benefit from addition of non-statin therapies. We assessed the relationship between lower low-density lipoprotein cholesterol (LDL-C) and major adverse cardiovascular events (MACE) risk reduction during alirocumab phase III ODYSSEY trials among these subgroups.
Patient data were pooled from nine trials comparing alirocumab with control (placebo/ezetimibe), predominantly on background maximally tolerated statin. Patients with baseline ASCVD were stratified into subgroups with DM, CKD or PoVD, or without comorbidities, and between-group relative and absolute benefits were compared.
Among 3505 patients with ASCVD, 1573 had no comorbidities, 981 had DM, 660 had CKD and 943 had PoVD, with overlap between comorbidities; mean baseline LDL-C levels were 119 (ASCVD overall), 123, 117, 114 and 113 mg/dL, respectively. Overall, each 39 mg/dL lower on-study LDL-C was associated with a 25% lower MACE risk, hazard ratio 0.75 (95% confidence interval, 0.62-0.90, p = 0.0023), with a similar lower risk observed in each very high-risk subgroup (DM, CKD or PoVD; 30-35%) but not in the subgroup without these comorbidities (9%). Absolute benefits were greater for very high-risk subgroups; lowering LDL-C from 120 to 40 mg/dL would result in 2.76-4.35 fewer MACE/100 patient-years versus 0.3 for no comorbidities.
Among patients with ASCVD and mean baseline LDL-C >100 mg/dL, patients with DM, CKD or PoVD appeared to derive greater absolute cardiovascular benefits from further LDL-C reduction than those without.
指南推荐高强度他汀类药物用于动脉粥样硬化性心血管疾病（ASCVD）患者。合并增加心血管风险的合并症的亚组，如糖尿病（DM）、慢性肾脏病（CKD）或多血管疾病（PoVD），可能从添加非他汀类药物治疗中获得更大的绝对获益。我们评估了在这些亚组中，在 ODYSSEY 试验 III 期的阿利西尤单抗阶段，较低的低密度脂蛋白胆固醇（LDL-C）与主要不良心血管事件（MACE）风险降低之间的关系。
患者数据来自 9 项比较阿利西尤单抗与对照（安慰剂/依折麦布）的试验，主要基于最大耐受他汀类药物的背景治疗。将基线 ASCVD 的患者分为无合并症、合并 DM、合并 CKD 或合并 PoVD 的亚组，以及无合并症的患者，并比较组间的相对和绝对获益。
在 3505 例 ASCVD 患者中，1573 例无合并症，981 例合并 DM，660 例合并 CKD，943 例合并 PoVD，合并症之间存在重叠；平均基线 LDL-C 水平分别为 119（ASCVD 整体）、123、117、114 和 113mg/dL。总体而言，研究中 LDL-C 每降低 39mg/dL，MACE 风险降低 25%，危险比为 0.75（95%置信区间为 0.62-0.90，p=0.0023），在每个极高危亚组（DM、CKD 或 PoVD；30-35%）中观察到相似的低风险，但在无这些合并症的亚组（9%）中未观察到。极高危亚组的绝对获益更大；将 LDL-C 从 120 降低至 40mg/dL，与无合并症相比，每 100 患者年将减少 2.76-4.35 次 MACE。
在 ASCVD 且基线 LDL-C＞100mg/dL 的患者中，与无合并症的患者相比，合并 DM、CKD 或 PoVD 的患者从进一步降低 LDL-C 中获得更大的绝对心血管获益。
