ImportanceThe ATP citrate lyase (ACL) inhibitor, bempedoic acid, reduces low-density lipoprotein cholesterol (LDL-C) level and major adverse cardiovascular events (MACE) by 13% in patients at high cardiovascular risk with intolerance of statin and high-intensity statin medications. The effects of bempedoic acid on total cardiovascular events remain unknown.ObjectiveTo determine the impact of bempedoic acid on the total incidence of MACE.Design, Setting, and ParticipantsIncluded in this prespecified analysis of the Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes trial were patients with, or at high risk for, cardiovascular disease, with hypercholesterolemia and inability to take guideline-recommended statins. Study data were analyzed from December 2016 to November 2022.InterventionsPatients were randomly assigned to treatment with bempedoic acid or placebo daily.Main Outcomes and MeasuresThe primary end point was the time to first event for a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization (MACE-4). The key secondary end point was time to first event for cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (MACE-3). This prespecified analysis compared the total number of cardiovascular events in the treatment groups.ResultsA total of 13 970 patients (mean [SD] age, 65 [9] years; 7230 male [51.8%]) were included in the study. A total of 9764 participants (69.9%) had prior atherosclerotic cardiovascular disease and a baseline LDL-C level of 139 mg/dL; treatment with bempedoic acid resulted in a 21% reduction in LDL-C level and a 22% reduction in high-sensitivity C-reactive protein (hsCRP) level at 6 months. Median (IQR) follow-up was 3.4 (3.1-3.9) years. A total of 1746 positively adjudicated first MACE-4 events and 915 additional MACE events in 612 patients were recorded, with coronary revascularization representing 32.8% (573 of 1746) of first events and 69.4% (635 of 915) of additional events. For the total incidence of cardiovascular events, treatment with bempedoic acid was associated with a reduction in risk of MACE-4 (hazard ratio [HR], 0.80; 95% CI, 0.72-0.89; P <.001), MACE-3 (HR, 0.83; 95% CI, 0.73-0.93; P = .002), myocardial infarction (HR, 0.69; 95% CI, 0.58-0.83; P < .001), and coronary revascularization (HR, 0.78; 95% CI, 0.68-0.89; P <.001), although no statistically significant difference was observed for stroke (HR, 0.80; 95% CI, 0.63-1.03). A lower HR for protection with bempedoic acid was observed with increasing number of MACE events experienced by patients.Conclusion and RelevanceLowering LDL-C level with bempedoic acid reduced the total number of cardiovascular events in patients with high cardiovascular risk, statin therapy intolerance, and elevated LDL-C levels.

中文翻译：

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Bempedoic Acid 对总心血管事件的影响

重要性对于他汀类药物和高强度他汀类药物不耐受的高心血管风险患者，ATP 柠檬酸裂解酶 (ACL) 抑制剂 Bempedoic Acid 可将低密度脂蛋白胆固醇 (LDL-C) 水平和主要不良心血管事件 (MACE) 降低 13%药物。Bempedoic Acid 对总心血管事件的影响仍不清楚。目的确定 bempedoic Acid 对 MACE 总发生率的影响。设计、设置和参与者包括在通过 Bempedoic Acid（一种 ACL 抑制方案）降低胆固醇的预先指定分析中（明确）结果试验的对象是患有心血管疾病或高风险心血管疾病、高胆固醇血症且无法服用指南推荐的他汀类药物的患者。分析了 2016 年 12 月至 2022 年 11 月的研究数据。 干预措施 患者每天被随机分配接受 Bempedoic Acid 或安慰剂治疗。 主要结局和措施 主要终点是心血管死亡、非致命性心肌梗死、非致命性中风复合事件的首次事件发生时间，或冠状动脉血运重建（MACE-4）。关键的次要终点是心血管死亡、非致命性心肌梗死和非致命性卒中（MACE-3）首次发生事件的时间。这项预先指定的分析比较了治疗组中心血管事件的总数。 结果 研究共纳入 13 970 名患者（平均 [SD] 年龄，65 [9] 岁；7230 名男性 [51.8%]）。共有 9764 名参与者 (69.9%) 患有动脉粥样硬化性心血管疾病，基线 LDL-C 水平为 139 mg/dL；6 个月时，Bempedoic Acid 治疗使 LDL-C 水平降低 21%，高敏 C 反应蛋白 (hsCRP) 水平降低 22%。中位随访时间 (IQR) 为 3.4 (3.1-3.9) 年。612 名患者共记录了 1746 例阳性判定的首次 MACE-4 事件和 915 例额外 MACE 事件，其中冠状动脉血运重建占首次事件的 32.8%（1746 例中的 573 例）和额外事件的 69.4%（915 例中的 635 例）。对于心血管事件的总发生率，bempedoic 酸治疗与 MACE-4 风险降低相关（风险比 [HR]，0.80；95% CI，0.72-0.89；磷<.001)，MACE-3(HR，0.83；95% CI，0.73-0.93；磷= .002)，心肌梗塞（HR，0.69；95% CI，0.58-0.83；磷< .001）和冠状动脉血运重建（HR，0.78；95% CI，0.68-0.89；磷<.001），但对于中风没有观察到统计学上的显着差异（HR，0.80；95% CI，0.63-1.03）。随着患者经历的 MACE 事件数量的增加，观察到 Bempedoic Acid 的保护 HR 较低。结论和相关性使用 Bempedoic Acid 降低 LDL-C 水平可减少高心血管风险、他汀类药物治疗不耐受和升高的患者的心血管事件总数。低密度脂蛋白胆固醇水平。