1、,1,稳定性冠心病的调脂治疗策略,COURAGE研究证实药物治疗在稳定性冠心病治疗中的基石地位,HR 1.05*(0.87-1.27)P = 0.62,Boden WE et al. N Engl J Med. 2007;356.,总死亡率与心梗,*Unadjusted,Medical therapy PCI + medical therapy,No. at riskMedical therapy1138101795983463840819230PCI1149101395283363741720035,无事件生存,0,2,4,7,0,0.5,0.6,0.7,0.8,1.0,0.9,Years,
2、6,5,3,血脂目标LDL-C:60-85mg/dl辛伐他汀依折麦布HDL-C:大于40mg/dlTG:小于150mg/dl,3,辛伐他汀显著降低所有原因的死亡率,5.4年时，辛伐他汀显著降低冠脉死亡的危险达42%,30%P=0.0003,200,150,100,50,0,n=189,n=111,累积死亡人数,安慰剂,辛伐他汀,P=0.00001,对死亡率的影响,Lancet 1994;344: 1383-89. Am J Cardiol 1995;76:64C-68C.,4S: 揭开他汀治疗冠心病序幕,4,辛伐他汀显著降低主要冠脉事件的危险,辛伐他汀显著降低心肌血管重建术的危险,34%P0.
3、00001,37%P0.00001,Lancet 1994;344: 1383-89; Am J Cardiol 1995;76:64C-68C.,对冠脉事件和心肌血管重建术的影响,4S: 揭开他汀治疗冠心病序幕,5,HPS回答的主要问题:疾病史,Lancet 2002;360:7-22.,999,1250,(23.5%),(29.4%),460,591,(18.9%),(24.2%),172,212,(18.7%),(23.6%),327,420,(24.7%),(30.5%),276,367,(13.8%),(18.6%),(P0.00001),2033,2585,(19.8%),(25.
4、2%),0.4,0.6,0.8,1.0,1.2,1.4,心梗史,其他冠心病(非心梗),无冠心病史,脑血管疾病,外周血管疾病,糖尿病,所有患者主要血管事件,降低24%,危险性比值和 95%可信区间,辛伐他汀,安慰剂,(10,269),(10,267),他汀更好,安慰剂更好,6,吸烟,406,531,(15.7%),(20.6%),非常规吸烟者,1298,1638,(20.8%),(26.3%),戒烟者,329,416,(22.8%),(28.4%),吸烟者,治疗的高血压,942,1195,(22.4%),(28.1%),是,1091,1390,(18.0%),(23.1%),否,(P0.0000
5、1),2033,2585,(19.8%),(25.2%),所有患者主要血管事件,0.4,0.6,0.8,1.0,1.2,1.4,降低24%,基线特征,危险性比值和 95%可信区间,辛伐他汀,安慰剂,(10,269),(10,267),他汀更好,安慰剂更好,HPS回答的主要问题:伴随危险因素,Lancet 2002;360:7-22.,7,HPS回答的主要问题：基线血脂水平,LDL胆固醇(mg/dl),282,358,(16.4%),(21.0%), 100,668,871,(18.9%),(24.7%),100 130,1083,1356,(21.6%),(26.9%),130,(P0.000
6、01),2033,2585,(19.8%),(25.2%),所有患者主要血管事件,0.4,0.6,0.8,1.0,1.2,1.4,降低24%,入选时血脂水平,危险性比值和 95%可信区间,他汀更好,安慰剂更好,辛伐他汀,安慰剂,(10,269),(10,267),Lancet 2002;360:7-22.,8,831,1091,(16.9%),(22.1%), 65,512,665,(20.9%),(27.2%),65 - 69,548,620,(23.8%),(27.7%),70 - 74,142,209,(23.1%),(32.3%),75,1666,2135,(21.6%),(27.6%
7、),367,450,(14.4%),(17.7%),(P50%降幅大剂量 v.s. 标准剂量,高危患者LDL-C小于100mg/dl依据来源于多项流行病学研究,Keys A, Arvanis C, Blackburn H. Seven countries:a multivariate analysis of death and coronary heartdisease. Cambridge, MA: Harvard University Press,1980; 381.Law MR, Wald NJ, Thompson SG. By how muchand how quickly does
8、reduction in serum cholesterolconcentration lower risk of ischaemic heart disease?BMJ 1994;308:367-72.Law MR. Lowering heart disease risk with cholesterolreduction: evidence from observational studies andclinical trials. Eur Heart J Suppl 1999;(suppl S):S3-S8.Grundy SM, Wilhelmsen L, Rose G, Campbel
9、l RWF,Assmann G. Coronary heart disease in high-riskpopulations: lessons from Finland. Eur Heart J1990;11:462-71.Peoples Republic of China-United States Cardiovascularand Cardiopulmonary Epidemiology Research Group.An epidemiological study of cardiovascular andcardiopulmonary disease risk factors in
10、 four populationsin the Peoples Republic of China: baseline report fromthe P.R.C.-U.S.A. Collaborative Study. Circulation1992;85:1083-96.Law MR, Thompson SG, Wald NJ. Assessing possiblehazards of reducing serum cholesterol. BMJ1994;308:373-9.Law MR, Wald NJ, Wu T, Hackshaw A, Bailey A.Systematic und
11、erestimation of association betweenserum cholesterol concentration and ischaemic heartdisease in observational studies: data from the BUPAstudy. BMJ 1994;308:363-6.,13,稳定性冠心病他汀研究第一阶段终点证据 (活性药物 v.s. 安慰剂),Lancet 1994: 344:1383-89; Lancet 2002; 360: 722; N Engl J Med 1998; 339: 1349-57; N Engl J Med 19
12、96; 335:1001-9; JAMA.2002; 287: 3215-3222,14,CTT (Meta)对稳定性冠心病降脂治疗的启示(LDL-C降低与获益的关系),每降低1mmol/l LDL-C, 主要冠脉事件风险降低23%,每降低1mmol/l LDL-C，主要血管事件风险降低21%,Lancet 2005; 366: 1267-78,相比安慰剂，通过中等剂量他汀治疗把LDL-C降低到100mg/dL，降幅约30%,15,CTT (Meta)对稳定性冠心病降脂治疗的启示(总死亡率),Lancet 2005; 366: 1267-78,每降低1mmol/L LDL-C对具体原因死亡的影
13、响,中等剂量他汀降低LDL-C治疗，可以显著降低冠心病死亡和主要血管事件的死亡。,16,CTT (Meta)对稳定性冠心病降脂治疗的启示(安全性),Lancet 2005; 366: 1267-78,每降低1mmol/L LDL-C对非血管死亡的影响,每降低1mmol/L LDL-C对癌症发生率的影响,使用中等剂量他汀降低LDL-C治疗，不会增加非血管死亡和癌症发生率。,17,中国血脂指南关于稳定性冠心病的治疗建议mg/dl(mmol/L),LDL-C 80(2.07),LDL-C 80(2.07),LDL-C 80(2.07),TC 120(3.1),TC 160(4.14),TC 160(
14、4.14),极高危：急性冠脉综合征，或缺血性心血管病合并糖尿病,LDL-C 100(2.6),LDL-C 100(2.6),LDL-C 100(2.6),TC 160(4.14),TC 160(4.14),TC 160(4.14),高危：CHD或CHD等危症，或10年危险性1015,LDL-C 130(3.41),LDL-C 160(4.14),LDL-C 130(3.41),TC 200(5.2),TC 240（6.21）,TC 200(5.2),中危：(10年危险性5-10),LDL-C 160(4.14),LDL-C 190(4.92),LDL-C 160(4.14),TC240(6.2
15、1),TC270(6.99),TC240(6.21),低危：(10年危险性5%),治疗目标值,药物治疗开始,TLC开始,危险等级,18,ATP III 修订版关于稳定性冠心病的治疗建议,Circulation 2004;110;227-239,# 基线LDL-C100mg/dL,药物治疗可选,危险分层 LDL-C目标值 启用 TLC 考虑药物治疗高度危险 100mg/dL#冠心病或其等危症 可选:20%) 考虑药物选用)中度高危 130mg/dL 130mg/dL 130mg/dL2+ 危险因子 可选:100mg/dL (100-129mg/dL:(10年危险10-20%) 考虑药物选用)中度
16、危险 130mg/dL 130mg/dL 160mg/dL2+ 危险因子(10年危险 10%)低度危险 50%降幅 大剂量 v.s. 标准剂量,第一阶段 治疗后LDL-C：100mg/dL，30-40%降幅 标准剂量 v.s. 安慰剂,*LDL-C 100 mg/dl is the optimal target level set by the National Cholesterol Education Program (NCEP) ATP III. The other two LDL-C ranges were defined prior to randomization and were
17、 based on NCEP guidelines.Adapted from MRC/BHF Heart Protection Study Final Results. Presented at the European Atherosclerosis Society. Salzburg, Austria, July 2002 (www.ctsu.ox.ac.uk); Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults JAMA 2001;285:2486-2497.,
18、0.4 0.6 0.8 1.0 1.2 1.4,Risk ratio and 95% CI,Simvastatin Placebo betterbetter,RRR24P=0.0001,HPS研究冠心病高危患者可能存在更低的LDL-C目标,30,21,JAMA. 2005;294:2437-2445,N Engl J Med 2005;352:1425-35.,文献,0.07,-11%,冠脉死亡，非致命心梗，心肺复苏,8888Ato 80 v.s. Sim 20,IDEAL(稳定性CHD),阿托伐他汀/辛伐他汀,-22%,相对风险下降,60%的患者经历了没有降脂治疗相同的血管事件。所以未来降脂
19、治疗不是去寻找更强的他汀和更大的剂量，而是与他汀的联合治疗，关注HDL-C，TG，颗粒大小和斑块不稳定的其他机制。,Circulation.2006;113:1382-1384.,*入选LDL-C:130-250mg/dL, 阿托伐他汀10mg 8周洗脱, LDL-C2.5 mmol/L (97 mg/dL),1g,MK-0524A,2g,按1:1比例盲法活性药物治疗,4年随访 + 2300 主要血管事件,周,随机化入组 3个月随访 6个月随访,*患者在入组前的12-16周, 服用辛伐他汀40mg或依则麦布/辛伐他汀 10/40mg.,*,Data on file MSD,入选患者: 冠心病, 冠心病高危患者(糖尿病,中风, 高血压, 外周血管疾病), 低胆固醇高危患者, 老年高危患者, 女性高危患者. 与HPS研究完全一致,研究假说：MK0524A1-2g升高HDL-C达20，进一步减少HPS主要研究患者群主要血管事件20,
