Goldenberg Ilan, Benderly Michal, Goldbourt Uri
Heart Institute, Shiba Medical Center Tel Hashomer, Israel.
Vasc Health Risk Manag. 2008;4(1):131-41. doi: 10.2147/vhrm.2008.04.01.131.
Low-density lipoprotein-cholesterol (LDL-C) is a well established coronary heart disease (CHD) risk factor. However, the ability of this metabolic risk factor alone to identify individuals at rigk for future CHD events is limited. The raised triglycerides-low high-density lipoprotein-cholesterol (HDL-C) dyslipidaemia was shown to be an important cardiovascular risk factor independently of LDL-C levels. Fibric acid derivatives (fibrates) have been used in clinical practice for more than 2 decades as a class of agents known to decrease triglyceride levels while substantially increasing HDL-C levels. Through peroxisome proliferator-activated alpha-receptors, fibrates have a significant impact on the synthesis of several apolipoproteins and enzymes of lipoprotein metabolism as well as on the expression of several genes involved in fibrinolysis and inflammation. Data from recent primary and secondary prevention clinical trials demonstrate the efficacy of fibrate therapy in patients with the raised triglycerides-low HDL-C dyslipidaemia. This review summarizes current data regarding mechanism of action and the metbolic effects of fibrates, as well as results from major clinical trials on the efficacy of this mode of lipid lowering therapy. In addition, recent data from subgroup analyses of the Bezafibrate Infarction Prevention trial, demonstrating several important metabolic and long-term cardiovascular effects of bezafibrate therapy, are detailed.
低密度脂蛋白胆固醇(LDL-C)是一种公认的冠心病(CHD)危险因素。然而,仅靠这种代谢危险因素来识别未来有冠心病事件风险的个体的能力是有限的。甘油三酯升高-高密度脂蛋白胆固醇(HDL-C)降低的血脂异常被证明是一种独立于LDL-C水平的重要心血管危险因素。二十多年来,纤维酸衍生物(贝特类药物)一直在临床实践中作为一类已知可降低甘油三酯水平同时大幅提高HDL-C水平的药物使用。通过过氧化物酶体增殖物激活α受体,贝特类药物对几种载脂蛋白和脂蛋白代谢酶的合成以及对参与纤维蛋白溶解和炎症的几种基因的表达有重大影响。近期一级和二级预防临床试验的数据证明了贝特类药物治疗对甘油三酯升高-HDL-C降低的血脂异常患者的疗效。本综述总结了关于贝特类药物作用机制和代谢作用的当前数据,以及关于这种降脂治疗方式疗效的主要临床试验结果。此外,还详细介绍了非诺贝特预防心肌梗死试验亚组分析的近期数据,这些数据证明了非诺贝特治疗的几种重要代谢和长期心血管效应。