Mount Sinai Heart-Box 1030, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Eur Heart J. 2011 Apr;32(8):999-1005. doi: 10.1093/eurheartj/ehq374. Epub 2010 Nov 16.
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.
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).
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.
研究分泌型磷脂酶 A2（sPLA2）抑制对血浆脂蛋白的影响。分泌型磷脂酶 A2 同工酶通过包括脂蛋白修饰、保留和氧化在内的机制促进动脉粥样硬化。
磷脂酶水平和动脉粥样硬化的血清标志物 II（PLASMA II）是一项 II 期、随机、双盲、安慰剂对照的平行臂研究，研究了两种新型 sPLA2 抑制剂 1-H-吲哚-3-乙酰胺或瓦雷普拉迪布甲醚（Anthera Pharmaceuticals，海沃德，CA，美国）的每日一次剂量。135 例稳定型冠心病患者分别接受瓦雷普拉迪布甲醚 250mg 每日一次、瓦雷普拉迪布甲醚 500mg 每日一次或安慰剂治疗 8 周。瓦雷普拉迪布甲醚治疗导致 sPLA2 浓度、低密度脂蛋白（LDL）胆固醇和非高密度脂蛋白（HDL）胆固醇呈剂量依赖性的统计学显著降低，与安慰剂相比有显著差异。与安慰剂相比，瓦雷普拉迪布甲醚 500mg 每日一次可降低 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）和小 VLDL 颗粒浓度 24%（P = 0.030）。与基线相比，瓦雷普拉迪布甲醚 500mg 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）。
致动脉粥样硬化脂蛋白的减少表明瓦雷普拉迪布甲醚 500mg 每日一次可能是一种有效的抗动脉粥样硬化药物。试验在 ClinicalTrials.gov 注册，标识符：NCT00525954。
