Cardiology Department. Hospital IMED. Elche, Spain (Dr Cordero); Grupo de Investigación Cardiovascular (GRINCAVA). Universidad Miguel Hernández. Elche, Spain (Dr Cordero); Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV). Spain (Drs Cordero, Badimon, Rodriguez-Manero, Bonanad, Vilahur and González-Juanatey).
Hospital Universitario de Jaén, Jaén, Spain (Dr Olmo).
J Clin Lipidol. 2023 Sep-Oct;17(5):602-611. doi: 10.1016/j.jacl.2023.08.006. Epub 2023 Aug 22.
Statins are the cornerstone of lipid-lowering therapy (LLT) for reduction of low-density lipoprotein cholesterol (LDLc) levels and high percentage of patients require LLT combinations or alternative treatments for adequate LDLc control.
We performed an intention-to-treat meta-analysis of published data of phase III trials evaluating LLT efficacy on major adverse cardiovascular events (MACE). The primary endpoint was MACE incidence, as reported in each trial, and secondary analyses included myocardial infarction, stroke and mortality.
Eleven clinical trials and 135,688 patients were included; seven trials tested high intensity LLT and 4 LLT combinations. Intensive LLT reduced MACE risk by 15% (12.03% vs. 13.79%, HR: 0.85 95% CI 0.80-0.90; p<0.001). The number needed to treat was 56 patients. Meta-regression analyses showed a linear correlation between absolute LDLc reductions and the risk of MACE. Significant reductions in myocardial infarction (HR: 0.83, 95% CI 0.80-0.86) and stroke (HR: 0.81, 95% CI 0.75-0.87) were observed. Cardiovascular death rate was 3.32% in LLT treatment arm vs. 3.56% in controls, resulting in a HR: 0.94 (95% CI 0.88-0.99; p = 0.03); no effect on all-cause mortality was observed (HR: 0.97 95% CI 0.93-1.01; p = 0.09). The sensitivity analyses verified the lack of heterogeneity, except for MACE that was mainly driven by the divergent results of the 2 trials. Small study effect was detected for the assessment of mortality.
Current evidence consistently supports the efficacy of available intensity LLT for LDLc decrease on MACE and cardiovascular mortality reduction.
他汀类药物是降低低密度脂蛋白胆固醇（LDLc）水平的降脂治疗（LLT）的基石，大多数患者需要 LLT 联合治疗或替代治疗以达到充分的 LDLc 控制。
我们对评估 LLT 对主要不良心血管事件（MACE）疗效的 III 期试验的已发表数据进行了意向治疗荟萃分析。主要终点是每个试验报告的 MACE 发生率，次要分析包括心肌梗死、卒中和死亡率。
纳入了 11 项临床试验和 135688 名患者；7 项试验测试了高强度 LLT，4 项 LLT 联合治疗。强化 LLT 降低了 15%的 MACE 风险（12.03% vs. 13.79%，HR：0.85 95%CI 0.80-0.90；p<0.001）。需要治疗的患者数为 56 例。荟萃回归分析显示，绝对 LDLc 降低与 MACE 风险之间存在线性相关性。心肌梗死（HR：0.83，95%CI 0.80-0.86）和卒中（HR：0.81，95%CI 0.75-0.87）的风险显著降低。在 LLT 治疗组的心血管死亡率为 3.32%，对照组为 3.56%，导致 HR：0.94（95%CI 0.88-0.99；p=0.03）；未观察到全因死亡率的影响（HR：0.97 95%CI 0.93-1.01；p=0.09）。敏感性分析验证了除 MACE 外，其余均不存在异质性，而 MACE 主要受 2 项试验结果分歧的驱动。对于死亡率的评估，检测到了小样本研究的影响。
目前的证据一致支持现有强度 LLT 降低 LDLc 对 MACE 和心血管死亡率降低的疗效。
