Monash Cardiovascular Research Centre, Monash University, Melbourne, Australia.
Department of Cardiovascular Medicine, Cleveland Clinic and Cleveland Clinic Coordinating Center for Clinical Research.
Am Heart J. 2021 May;235:104-112. doi: 10.1016/j.ahj.2020.10.060. Epub 2020 Oct 24.
Although statins play a pivotal role in the prevention of atherosclerotic cardiovascular disease, many patients fail to achieve recommended lipid levels due to statin-associated muscle symptoms. Bempedoic acid is an oral pro-drug that is activated in the liver and inhibits cholesterol synthesis in hepatocytes, but is not activated in skeletal muscle which has the potential to avoid muscle-related adverse events. Accordingly, this agent effectively lowers atherogenic lipoproteins in patients who experience statin-associated muscle symptoms. However, the effects of bempedoic acid on cardiovascular morbidity and mortality have not been studied. STUDY DESIGN: Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes is a randomized, double-blind, placebo-controlled clinical trial. Included patients must have all of the following: (i) established atherosclerotic cardiovascular disease or have a high risk of developing atherosclerotic cardiovascular disease, (ii) documented statin intolerance, and (iii) an LDL-C ≥100 mg/dL on maximally-tolerated lipid-lowering therapy. The study randomized 14,014 patients to treatment with bempedoic acid 180 mg daily or matching placebo on a background of guideline-directed medical therapy. The primary outcome is a composite of the time to first cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. The trial will continue until 1620 patients experience a primary endpoint, with a minimum of 810 hard ischemic events (cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) and minimum treatment duration of 36 months and a projected median treatment exposure of 42 months. CONCLUSIONS: CLEAR Outcomes will determine whether bempedoic acid 180 mg daily reduces the incidence of adverse cardiovascular events in high vascular risk patients with documented statin intolerance and elevated LDL-C levels.
虽然他汀类药物在预防动脉粥样硬化性心血管疾病方面发挥着关键作用，但由于他汀类药物相关的肌肉症状，许多患者无法达到推荐的血脂水平。贝匹地酸是一种口服前药，在肝脏中被激活并抑制肝细胞中的胆固醇合成，但在骨骼肌中不被激活，这有可能避免与肌肉相关的不良事件。因此，该药物可有效降低发生他汀类药物相关肌肉症状患者的致动脉粥样硬化脂蛋白。然而，贝匹地酸对心血管发病率和死亡率的影响尚未得到研究。研究设计：通过贝匹地酸降低胆固醇，一种 ACL 抑制方案（CLEAR）结局是一项随机、双盲、安慰剂对照的临床试验。纳入的患者必须符合以下所有条件：（i）患有明确的动脉粥样硬化性心血管疾病或有发生动脉粥样硬化性心血管疾病的高风险，（ii）有他汀类药物不耐受的病史，以及（iii）在最大耐受的降脂治疗下 LDL-C≥100mg/dL。该研究将 14014 名患者随机分为贝匹地酸 180mg 每日治疗组或匹配的安慰剂组，同时进行指南指导的医学治疗。主要终点是首次心血管死亡、非致死性心肌梗死、非致死性卒中和冠状动脉血运重建的时间复合终点。该试验将继续进行，直到 1620 名患者出现主要终点事件，需要至少 810 例硬缺血事件（心血管死亡、非致死性心肌梗死或非致死性卒中）和至少 36 个月的治疗时间，预计中位治疗暴露时间为 42 个月。结论：CLEAR 结局将确定贝匹地酸 180mg 每日治疗是否能降低有明确他汀类药物不耐受和升高的 LDL-C 水平的高血管风险患者不良心血管事件的发生率。
