美国圣路易斯华盛顿大学医学院Anne C. Goldberg联合俄勒冈健康与科学大学P. Barton Duell研究组宣布他们揭示了Bempedoic酸对心血管疾病高危患者低密度脂蛋白胆固醇的影响。相关论文2019年11月12日发表在《美国医学会杂志》上。

对于那些不能通过有效的降脂治疗来充分降低低密度脂蛋白胆固醇（LDL-C）水平的患者，需要额外的治疗方案。

2016年11月至2018年9月，研究组在北美和欧洲的91个临床试验点进行了一项临床3期、随机、双盲、安慰剂对照的临床试验，招募了779例动脉粥样硬化性心血管疾病或杂合子家族性高胆固醇血症的患者，LDL-C水平超过70 mg/dL，同时接受最大耐受的降脂治疗。按2：1将患者随机分组，其中522例接受Bempedoic酸治疗，257例接受安慰剂治疗，为期52周。

共有740例（95.0%）患者完成了试验。基线时的LDL-C水平为120.4 mg/dL。第12周时，Bempedoic酸组的LDL-C水平降低了15.1%，安慰剂组却上升了2.4%，差异显著。Bempedoic酸组的非高密度脂蛋白胆固醇、总胆固醇、载脂蛋白B和高敏C-反应蛋白分别比基线降低了10.8%、9.9%、9.3%和18.7%，而安慰剂组则分别增加了2.3%、1.3%、3.7%，高敏C-反应蛋白降低了9.9%，两组间差异具有统计学意义。Bempedoic酸组中鼻咽炎、尿路感染和高尿酸血症等不良反应的发生率分别为5.2%、5.0%和4.2%，安慰剂组则分别为5.1%、1.9%和1.9%。

总之，对于高风险心血管疾病的患者，在接受最大耐受他汀类药物治疗的同时，添加Bempedoic酸，与安慰剂相比，可显著降低LDL-C水平，并维持超过12周。仍需进一步研究来评估该方法的耐久性、临床效果以及长期的安全性。

附：英文原文

Title: Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease: The CLEAR Wisdom Randomized Clinical Trial

Author: Anne C. Goldberg, Lawrence A. Leiter, Erik S. G. Stroes, Seth J. Baum, Jeffrey C. Hanselman, LeAnne T. Bloedon, Narendra D. Lalwani, Pragna M. Patel, Xin Zhao, P. Barton Duell

Issue&Volume: 2019/11/12

Abstract:

Importance  Additional treatment options are needed for patients who do not achieve sufficient reduction in low-density lipoprotein cholesterol (LDL-C) level with available lipid-lowering therapies.

Objective  To assess the efficacy of bempedoic acid vs placebo in patients at high cardiovascular risk receiving maximally tolerated lipid-lowering therapy.

Design, Setting, and Participants  Phase 3, randomized, double-blind, placebo-controlled clinical trial conducted at 91 clinical sites in North America and Europe from November 2016 to September 2018, with a final date of follow-up of September 22, 2018. A total of 779 patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both met randomization criteria, which included LDL-C level 70 mg/dL (1.8 mmol/L) or greater while receiving maximally tolerated lipid-lowering therapy.

Interventions  Patients were randomized 2:1 to treatment with bempedoic acid (180 mg) (n = 522) or placebo (n = 257) once daily for 52 weeks.

Main Outcomes and Measures  The primary end point was percent change from baseline in LDL-C level at week 12. Secondary measures included changes in levels of lipids, lipoproteins, and biomarkers.

Results  Among 779 randomized patients (mean age, 64.3 years; 283 women [36.3%]), 740 (95.0%) completed the trial. At baseline, mean LDL-C level was 120.4 (SD, 37.9) mg/dL. Bempedoic acid lowered LDL-C levels significantly more than placebo at week 12 (–15.1% vs 2.4%, respectively; difference, –17.4% [95% CI, –21.0% to –13.9%]; P < .001). Significant reductions with bempedoic acid vs placebo were observed at week 12 for non–high-density lipoprotein cholesterol (–10.8% vs 2.3%; difference, –13.0% [95% CI, –16.3% to –9.8%]; P < .001), total cholesterol (–9.9% vs 1.3%; difference, –11.2% [95% CI, –13.6% to –8.8%]; P < .001), apolipoprotein B (–9.3% vs 3.7%; difference, –13.0% [95% CI, –16.1% to –9.9%]; P < .001), and high-sensitivity C-reactive protein (median, –18.7% vs –9.4%; difference, –8.7% [asymptotic confidence limits, –17.2% to –0.4%]; P = .04). Common adverse events included nasopharyngitis (5.2% vs 5.1% with bempedoic acid and placebo, respectively), urinary tract infection (5.0% vs 1.9%), and hyperuricemia (4.2% vs 1.9%).

Conclusions and Relevance  Among patients at high risk for cardiovascular disease receiving maximally tolerated statins, the addition of bempedoic acid compared with placebo resulted in a significant lowering of LDL-C level over 12 weeks. Further research is needed to assess the durability and clinical effect as well as long-term safety.

DOI: 10.1001/jama.2019.16585

Source: https://jamanetwork.com/journals/jama/fullarticle/2754792