Ducobu J, Scheen A J, Legat P, De Backer G, Van Gaal L, Velkeniers B, Kartounian J, Maes M, Hermans M
Service de Université Mons Hainaut, Belgique.
Rev Med Liege. 2009 Oct;64(10):512-8.
The demography of dyslipidemia has changed towards a more complex atherogenic dyslipidemia involving increased levels of LDL cholesterol, in particular highly atherogenic small dense particles, hypertriglyceridemia and low HDL cholesterol, together with increased levels of markers of inflammation, thrombogenesis and endothelial dysfunction. Statins were shown to significantly lower cardiovascular morbidity and mortality, but treated patients are still left with a high residual risk, in particular for those with metabolic syndrome, type 2 diabetes, or low HDL cholesterol levels. Fibrates have been shown to reduce plasma triglycerides and increase HDL cholesterol, while improving inflammation, thrombogenesis and endothelial dysfunction. Clinical trials with fibrates have demonstrated their potential to reduce cardiovascular morbidity and mortality too, often through other mechanisms than those of statins. Combination trials of statins with fibrates have shown a more complete improvement of lipid profile and risk markers than each class separately. In contrast with gemfibrozil, fenofibrate does not interact significantly with the pharmacokinetics of statins, and its combination with statins has been shown to have a low risk of muscular side-effects or liver toxicity. The ACCORD outcome trial is exploring possible benefits of the combination of fenofibrate with statins on morbidity and mortality of patients with type 2 diabetes.
血脂异常的人群特征已朝着更复杂的致动脉粥样硬化性血脂异常转变，这种异常包括低密度脂蛋白胆固醇水平升高，尤其是具有高度致动脉粥样硬化性的小而密颗粒、高甘油三酯血症和低高密度脂蛋白胆固醇，同时炎症、血栓形成和内皮功能障碍的标志物水平也升高。他汀类药物已被证明能显著降低心血管疾病的发病率和死亡率，但接受治疗的患者仍面临较高的残余风险，特别是对于那些患有代谢综合征、2型糖尿病或高密度脂蛋白胆固醇水平较低的患者。贝特类药物已被证明能降低血浆甘油三酯并提高高密度脂蛋白胆固醇水平，同时改善炎症、血栓形成和内皮功能障碍。贝特类药物的临床试验也证明了它们有降低心血管疾病发病率和死亡率的潜力，其作用机制往往与他汀类药物不同。他汀类药物与贝特类药物的联合试验显示，与单独使用每一类药物相比，联合使用能更全面地改善血脂谱和风险标志物。与吉非贝齐不同，非诺贝特与他汀类药物的药代动力学没有显著相互作用，并且已证明其与他汀类药物联合使用时肌肉副作用或肝毒性风险较低。ACCORD结局试验正在探索非诺贝特与他汀类药物联合使用对2型糖尿病患者发病率和死亡率的可能益处。
