他汀治疗_我们的已知与未知.pptVIP

Reference De Pinieux G, Chariot P, Ammi-Said M, et al. Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio. Br J Clin Pharmacol. 1996 Sep;42(3):333-337. Ellis CJ, Scott R. Statins and coenzyme Q10. Lancet. 2003;361(9363):1134-1135. 在他汀基础上加用ERN/LRPT未能显著减少主要终点事件发生风险 www.ctsu.ox.ac.uk/thrive/press_release.htm 主要终点事件发生率（%） P=NS 加用ERN/LRPT显著增加不良反应发生率 明确肌病 任何肌病 （中国患者） 任何肌病 （欧洲患者） ALT升高 3倍以上 P=0.001 P＜0.0001 不良反应事件发生率（%/年） P=0.008 European Heart Journal.2013. 加用ERN/LRPT后停药率显著增加 总停药率 因皮肤 原因停药 因胃肠道 原因停药 因肌肉骨骼 原因停药 糖尿病相关 原因停药 P＜0.0001 P＜0.0001 P＜0.0001 P＜0.0001 P＜0.0001 发生率（%） European Heart Journal.2013. 中国患者肌病发生率高于欧洲患者原因分析 中国患者与欧洲患者差异的主要原因可能是由于不同人种在接受他汀类药物时的血药浓度不同 肌病主要和他汀类的血药浓度相关，亚洲人（尤其中国人）接受他汀类药物时的血药浓度更高，也就更容易发生肌病 Lee 2005的研究文献中，瑞舒伐他汀在中国人中血药AUC是白种人的2.31倍，Cmax是白种人的2.36倍 烟酸会导致辛伐他汀血药浓度进一步升高1/3，烟酸+人种的双重作用导致了加用烟酸的中国患者肌病发生率是欧洲患者的10余倍 即使对中国患者来说，辛伐他汀40mg对这部分高危患者的心血管获益可远远超出其肌病发生率绝对值的微小升高 European Heart Journal.2013. * * * * Figure 1(a): IHD mortality (33 744 deaths) versus usual total cholesterol. Age-specific associations The hazard ratios are plotted on a floating absolute scale of risk (so each log hazard ratio has an appropriate variance assigned to it. NOTES: 1 mmol/L lower total cholesterol was associated with about a half , a third and a sixth lower IHD mortality in both sexes at ages 40-49, 50-69 70-89, respectively, throughout the main range of cholesterol in most developed countries, with no apparent threshold. Although the proportional differences in risk decrease with age, the absolute effects of cholesterol on annual IHD mortality rates are much greater at older than at younger ages. For example, the absolute difference in the annual risk of IHD death for a 1 mmol/L difference in total cholesterol was about 10 times greater at 80-89 than at 40-49 years of age. The Prospective Studies Collaboration provides information on the relationship between BP and vascular disease mort