Wheeler D C
Department of Nephrology, University Hospital NHS Trust, Birmingham, England.
Drugs. 1998 Oct;56(4):517-22. doi: 10.2165/00003495-199856040-00001.
Recent clinical trials have demonstrated beyond doubt that statins are effective in the prevention of acute coronary events. Critical analysis of these studies suggests that the benefits of statin therapy cannot be fully explained on the basis of reductions in plasma cholesterol levels. Accumulating knowledge of the actions of these drugs shows that they may prevent several processes that eventually lead to plaque rupture and the development of occlusive thrombosis, the basis of acute coronary events. Hence, statins may correct endothelial dysfunction (thus protecting against ischaemic injury), stabilise existing plaques and modify the coagulation pathway, thereby reducing the likelihood of a sudden vascular event. At a cellular level, these drugs inhibit the synthesis not just of cholesterol, but of other compounds important in cell proliferation. Antiproliferative effects have been demonstrated in vitro and may broaden the applications of statins to the treatment of noncardiovascular diseases. Finally, preliminary clinical studies indicate that as a result of immunosuppressive actions, statins may reduce the incidence of rejection following organ transplantation.
近期的临床试验已毫无疑问地证明,他汀类药物在预防急性冠脉事件方面是有效的。对这些研究的批判性分析表明,他汀类药物治疗的益处不能完全基于血浆胆固醇水平的降低来解释。对这些药物作用的认识不断积累,表明它们可能预防几个最终导致斑块破裂和闭塞性血栓形成(急性冠脉事件的基础)的过程。因此,他汀类药物可能纠正内皮功能障碍(从而预防缺血性损伤),稳定现有斑块并改变凝血途径,从而降低突发血管事件的可能性。在细胞水平上,这些药物不仅抑制胆固醇的合成,还抑制细胞增殖中重要的其他化合物的合成。体外实验已证实其具有抗增殖作用,这可能会拓宽他汀类药物在非心血管疾病治疗中的应用。最后,初步临床研究表明,由于其免疫抑制作用,他汀类药物可能降低器官移植后排斥反应的发生率。