Adis, a Wolters Kluwer Business, Auckland, New Zealand.
Drugs. 2011 Oct 1;71(14):1917-46. doi: 10.2165/11208090-000000000-00000.
Fenofibrate is a fibric acid derivative indicated for the treatment of severe hypertriglyceridaemia and mixed dyslipidaemia in patients who have not responded to nonpharmacological therapies. The lipid-modifying effects of fenofibrate are mediated by the activation of peroxisome proliferator-activated receptor-α. Fenofibrate also has nonlipid, pleiotropic effects (e.g. reducing levels of fibrinogen, C-reactive protein and various pro-inflammatory markers, and improving flow-mediated dilatation) that may contribute to its clinical efficacy, particularly in terms of improving microvascular outcomes. Fenofibrate improves the lipid profile (particularly triglyceride [TG] and high-density lipoprotein-cholesterol [HDL-C] levels) in patients with dyslipidaemia. Compared with statin monotherapy, fenofibrate monotherapy tends to improve TG and HDL-C levels to a significantly greater extent, whereas statins improve low-density lipoprotein-cholesterol (LDL-C) and total cholesterol levels to a significantly greater extent. Fenofibrate is also associated with promoting a shift from small, dense, atherogenic LDL particles to larger, less dense LDL particles. Combination therapy with a statin plus fenofibrate generally improves the lipid profile to a greater extent than monotherapy with either agent in patients with dyslipidaemia and/or type 2 diabetes mellitus or the metabolic syndrome. In the pivotal FIELD and ACCORD trials in patients with type 2 diabetes, fenofibrate did not significantly reduce the risk of coronary heart disease events to a greater extent than placebo, and simvastatin plus fenofibrate did not significantly reduce the risk of major cardiovascular (CV) events to a greater extent than simvastatin plus placebo. However, the risk of some nonfatal macrovascular events and the incidence of certain microvascular outcomes were reduced significantly more with fenofibrate than with placebo in the FIELD trial, and in the ACCORD trial, patients receiving simvastatin plus fenofibrate were less likely to experience progression of diabetic retinopathy than those receiving simvastatin plus placebo. Subgroup analyses in the FIELD and ACCORD Lipid trials indicate that fenofibrate is of the greatest benefit in decreasing CV events in patients with atherogenic dyslipidaemia. Fenofibrate is generally well tolerated when administered alone or in combination with a statin. Thus, in patients with dyslipidaemia, particularly atherogenic dyslipidaemia, fenofibrate is a useful treatment option either alone or in combination with a statin.
非诺贝特是一种纤维酸衍生物，用于治疗对非药物治疗无反应的严重高甘油三酯血症和混合性血脂异常患者。非诺贝特的脂质调节作用是通过激活过氧化物酶体增殖物激活受体-α来介导的。非诺贝特还具有非脂类、多效性作用（例如降低纤维蛋白原、C 反应蛋白和各种促炎标志物的水平，并改善血流介导的扩张），这可能有助于其临床疗效，特别是在改善微血管结局方面。非诺贝特可改善血脂异常患者的血脂谱（特别是甘油三酯[TG]和高密度脂蛋白胆固醇[HDL-C]水平）。与他汀类单药治疗相比，非诺贝特单药治疗更能显著改善 TG 和 HDL-C 水平，而他汀类药物更能显著改善低密度脂蛋白胆固醇[LDL-C]和总胆固醇水平。非诺贝特还与促进小而密、致动脉粥样硬化的 LDL 颗粒向更大、密度更低的 LDL 颗粒的转变有关。在血脂异常和/或 2 型糖尿病或代谢综合征患者中，与他汀类单药治疗相比，他汀类联合非诺贝特治疗通常能更显著地改善血脂谱。在 2 型糖尿病患者的 FIELD 和 ACCORD 关键性试验中，与安慰剂相比，非诺贝特并未更显著地降低冠心病事件风险，而辛伐他汀联合非诺贝特也并未更显著地降低主要心血管（CV）事件风险。然而，与 FIELD 试验中的安慰剂相比，非诺贝特更显著地降低了某些非致命性大血管事件的风险和某些微血管结局的发生率，在 ACCORD 试验中，与辛伐他汀联合安慰剂相比，接受辛伐他汀联合非诺贝特治疗的患者发生糖尿病视网膜病变进展的可能性更小。FIELD 和 ACCORD Lipid 试验的亚组分析表明，非诺贝特在降低致动脉粥样硬化性血脂异常患者的 CV 事件方面获益最大。非诺贝特单独或与他汀类药物联合使用时通常具有良好的耐受性。因此，对于血脂异常患者，特别是致动脉粥样硬化性血脂异常患者，非诺贝特是一种有用的治疗选择，无论是单独使用还是与他汀类药物联合使用。
