Laufs Ulrich, Lincoff A Michael, Nicholls Stephen J, Li Na, Bloedon LeAnne, Sasiela William J, Powell Heather A, Herout Peter M, Thompson Paul D, Nissen Steven E
Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig, Germany (Dr Laufs).
Department of Cardiovascular Medicine and Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Cleveland Clinic, Cleveland OH, USA (Drs Lincoff and Nissen).
J Clin Lipidol. 2025 Mar-Apr;19(2):337-347. doi: 10.1016/j.jacl.2024.12.014. Epub 2024 Dec 25.
Cholesterol Lowering via bEmpedoic Acid Regimen (CLEAR) outcomes, a randomized, double-blind, placebo-controlled cardiovascular outcomes trial, and the largest prospective database of patients with statin intolerance (SI), demonstrated that bempedoic acid reduces low-density lipoprotein cholesterol and cardiovascular risk in patients at high cardiovascular risk.
Assess baseline differences in SI symptoms and whether these influenced the clinical course during CLEAR outcomes.
Symptoms and impact of SI on daily living were recorded prior to randomization. This posthoc analysis grouped patients as reporting statin-associated muscle symptoms only (SAMS), nonmuscle adverse effects only (nonSAMS), or BOTH.
Of the 13,970 patients at baseline, 49% reported SAMS, 18% nonSAMS, and 33% BOTH. Moderate/severe impact on daily living was recorded for 62% SAMS, 48% nonSAMS, and 69% BOTH. Baseline lipid modifying treatment (LMT) was used in 43% SAMS, 36% nonSAMS, and 42% BOTH. Drop-in use of moderate/high-intensity statin at any time during the study was higher in the placebo group in all SI groups and higher in SAMS and BOTH vs nonSAMS, but was not generally maintained at study end. SAMS and BOTH groups had more muscle symptoms and higher rates of treatment discontinuation vs. nonSAMS but there was no difference between treatments.
Patients who reported SAMS, regardless of randomization to bempedoic acid or placebo, had higher rates of discontinuation, higher rates of skeletal muscle symptoms, and a greater percentage of patients to attempt statin rechallenge. These findings indicate patients with history of SAMS may have background factors impacting their tolerance to LMT and may require more focused clinical management.
NCT02993406.
通过贝派地酸方案降低胆固醇（CLEAR）结局研究是一项随机、双盲、安慰剂对照的心血管结局试验，也是他汀不耐受（SI）患者最大的前瞻性数据库，该研究表明贝派地酸可降低心血管高危患者的低密度脂蛋白胆固醇水平并降低心血管风险。
评估SI症状的基线差异以及这些差异是否会影响CLEAR结局研究期间的临床病程。
在随机分组前记录SI症状及其对日常生活的影响。这项事后分析将患者分为仅报告他汀相关肌肉症状（SAMS）、仅报告非肌肉不良反应（非SAMS）或两者皆有的患者。
在13970例基线患者中，49%报告有SAMS，18%报告有非SAMS，33%两者皆有。62%的SAMS患者、48%的非SAMS患者和69%两者皆有的患者记录有对日常生活的中度/重度影响。43%的SAMS患者、36%的非SAMS患者和42%两者皆有的患者在基线时使用了调脂治疗（LMT）。在所有SI组中，安慰剂组在研究期间任何时间使用中/高强度他汀的比例更高，且SAMS组和两者皆有的患者组高于非SAMS组，但在研究结束时一般未维持。与非SAMS组相比，SAMS组和两者皆有的患者组有更多的肌肉症状和更高的治疗中断率，但治疗组之间无差异。
报告有SAMS的患者，无论随机分配接受贝派地酸还是安慰剂治疗，其停药率更高、骨骼肌症状发生率更高，且尝试重新使用他汀的患者比例更大。这些发现表明，有SAMS病史的患者可能存在影响其对LMT耐受性的背景因素，可能需要更有针对性的临床管理。
NCT02993406。
