[医药卫生]积极降脂_有效防治冠心病----从指南到实践.pptVIP

Summary Point: Inhibition of cholesterol absorption combined with inhibition of cholesterol synthesis with a statin may provide greater LDL-C reductions given the complementary targets of exogenous and endogenous cholesterol with these approaches. Inhibition of endogenous cholesterol synthesis with statins is a common therapeutic approach to lowering LDL-C. Statins competitively inhibit HMG-CoA reductase, an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, a precursor of cholesterol. Given the dose-response limitations of statins1,2, known as the “Rule of Six”, and potential for increased liver transaminases with statin dose escalation, new approaches to lowering LDL-C are needed. New concepts in lipid management include the selective inhibition of cholesterol absorption via the exogenous pathway. Inhibition of dietary and biliary cholesterol absorption may provide an additional approach to reducing plasma cholesterol. * HPS中，辛伐他汀40mg/日的主要血管事件危险显著低于安慰剂治疗。与服用辛伐他汀比较，安慰剂组在第一年中有更多患者发生主要血管事件（包括非致命性MI、冠脉死亡、血运重建或脑卒中），并且随研究进展差异进一步增大。每1000名患者中，累计从辛伐他汀中获益及避免一次主要血管事件的患者数每年均有增加，第六年时已达到60±18人。HPS中辛伐他汀组患者的任意主要血管事件的相对危险为24% (p0.0001) 2。 * 由于安慰剂组中他汀使用者增多，因此HPS研究中辛伐他汀的临床受益可能被低估2。医学实践模式的转变及患者状况随时间的变化使安慰剂组中他汀使用者增多。若服用未列入研究的他汀与40mg辛伐他汀的降脂功效相当，则可以维持辛伐他汀或安慰剂治疗2。 总的来说，安慰剂组中服用未列入研究的他汀患者平均比例达17%，且整个研究中该比例呈持续增高（从随访第一年末的4%到第五年末的32%）2。另外，整个研究中辛伐他汀组中85%患者能够依从辛伐他汀治疗。在5年随访期间，每年患者的辛伐他汀依从率都超过80% 2。 * Adherence With Treatment At year 5, adherence was very high in both treatment groups (86% in the atorvastatin group and 92% in the simvastatin group).1 Overall adherence, defined as total study medication exposure as a percentageof total follow-up time, was 89% and 95% in the atorvastatin and simvastatin groups.2 References 1. Data on file. Pfizer Inc, New York, NY. 2. Pedersen TR, Faergeman O, Kastelein JJP, et al, for the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) Study Group. High-dose atorvastatin vs usual-dose simvastatin f