Randomized trial of an inhibitor of secretory phospholipase A2 on atherogenic lipoprotein subclasses in statin-treated patients with coronary heart disease.
Randomized trial of an inhibitor of secretory phospholipase A2 on atherogenic lipoprotein subclasses in statin-treated patients with coronary heart disease.
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DOI：
10.1093/eurheartj/ehq374
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发表时间：
2011-04
影响因子：
39.3
通讯作者：
R. Rosenson;M. Elliott;Y. Stasiv;C. Hislop
中科院分区：
文献类型：
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作者：
R. Rosenson;M. Elliott;Y. Stasiv;C. Hislop
目的探讨抑制分泌型磷脂酶A2（sPLA（2））对血浆脂蛋白的影响。分泌型磷脂酶A2同工酶通过脂蛋白修饰、滞留和氧化等机制促进动脉粥样硬化。方法和结果动脉粥样硬化II型磷脂酶水平和血清学标志物（PLASMA II）是一项II期、随机、双盲、安慰剂对照、平行臂研究，研究对象为新型sPLA（2）抑制剂1-H-吲哚-3-乙二醛酰胺或伐瑞拉迪甲基（Anthera Pharmaceuticals，海沃德，CA，USA），每日一次，两种剂量。135例稳定型冠心病患者接受伐瑞拉迪250 mg每日一次、伐瑞拉迪500 mg每日一次或安慰剂治疗8周。伐瑞拉迪甲基治疗导致sPLA（2）浓度、低密度脂蛋白（LDL）胆固醇和非高密度脂蛋白（HDL）胆固醇与安慰剂不同的统计学显著剂量依赖性降低。与安慰剂相比，伐瑞拉迪甲基500 mg每日一次降低LDL胆固醇15%（P < 0.001），非HDL胆固醇15%（P < 0.001），总极低密度脂蛋白（VLDL）颗粒浓度14%（P = 0.022），小VLDL颗粒浓度24%（P = 0.030）。相对于基线，伐瑞拉迪甲基500 mg每日一次可降低总LDL颗粒浓度（7%，P = 0.002）和小LDL颗粒浓度（11%，P = 0.014）。结论伐瑞拉迪500 mg每日一次可降低致动脉粥样硬化脂蛋白，可能是一种有效的抗动脉粥样硬化药物。试验注册于ClinicalTrials.gov，标识符：NCT 00525954。
AIMS To investigate the effects of secretory phospholipase A2 (sPLA(2)) inhibition on plasma lipoproteins. Secretory phospholipase A2 isoenzymes promote atherosclerosis by mechanisms that include lipoprotein modification, retention, and oxidation. METHODS AND RESULTS Phospholipase Levels And Serological Markers of Atherosclerosis II (PLASMA II) is a Phase II, randomized, double-blind, placebo-controlled parallel-arm study of two once-daily doses of the novel sPLA(2) inhibitor, 1-H-indole-3-glyoxamide or varespladib methyl (Anthera Pharmaceuticals, Hayward, CA, USA). One hundred and thirty-five stable coronary heart disease patients were treated with either varespladib methyl 250 mg once daily, varespladib methyl 500 mg once daily, or placebo for 8 weeks. Varespladib methyl treatment resulted in statistically significant dose-dependent reductions that were different from placebo in sPLA(2) concentration, low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (HDL) cholesterol. When compared with placebo, varespladib methyl 500 mg once daily reduced LDL cholesterol by 15% (P < 0.001), non-HDL cholesterol by 15% (P < 0.001), total very LDL (VLDL) particle concentration by 14% (P = 0.022), and small VLDL particle concentration by 24% (P = 0.030). Relative to baseline, varespladib methyl 500 mg once daily reduced total LDL particle concentration (7%, P = 0.002) and small LDL particle concentration (11%, P = 0.014). CONCLUSION Reductions in atherogenic lipoproteins suggest that varespladib methyl 500 mg once daily may be an effective anti-atherosclerotic agent. Trial registered at ClinicalTrials.gov, identifier: NCT00525954.