Paoletti R, Bolego C, Cignarella A
Department of Pharmacological Sciences, University of Milan, Italy.
Handb Exp Pharmacol. 2005(170):365-88. doi: 10.1007/3-540-27661-0_13.
Long- and short-term trials with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have demonstrated significant reductions in cardiovascular events in patients with and without history of coronary heart disease. Statins are well-established low-density lipoprotein (LDL)-lowering agents, but their clinical benefit is believed to result from a number of lipid and non-lipid effects beyond LDL lowering, including a rise in plasma high-density lipoprotein levels. Beyond improving the lipid profile, statins have additional non-lipid effects including benefit on endothelial function, inflammatory mediators, intima-media thickening, prothombotic factors that ultimately result in plaque stabilization. These effects arise through the inhibition of several mevalonate-derived metabolites other than cholesterol itself, which are involved in the control of different cellular functions. Although statins represent the gold standard in the prevention and treatment of coronary heart disease, combination therapy with other lipid-lowering drugs, as well as novel therapeutic indications, may increase their therapeutic potential.
对3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）进行的长期和短期试验表明，无论有无冠心病病史，患者的心血管事件均显著减少。他汀类药物是公认的降低低密度脂蛋白（LDL）的药物，但其临床益处被认为源于LDL降低之外的多种脂质和非脂质效应，包括血浆高密度脂蛋白水平的升高。除改善血脂谱外，他汀类药物还有其他非脂质效应，包括对内皮功能、炎症介质、内膜中层增厚、促血栓形成因子有益，最终导致斑块稳定。这些效应是通过抑制除胆固醇本身之外的几种甲羟戊酸衍生代谢物产生的，这些代谢物参与不同细胞功能的控制。尽管他汀类药物是预防和治疗冠心病的金标准，但与其他降脂药物的联合治疗以及新的治疗适应症可能会增加其治疗潜力。
