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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 risk Medical therapy 1138 1017 959 834 638 408 192 30 PCI 1149 1013 952 833 637 417 200 35,无事件 生存,0,2,4,7,0,0.5,0.6,
2、0.7,0.8,1.0,0.9,Years,6,5,3,1,血脂目标 LDL-C:60-85mg/dl辛伐他汀依折麦布 HDL-C:大于40mg/dl TG: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
3、件的危险,辛伐他汀显著降低心 肌血管重建术的危险,34% P0.00001,37% 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%),
4、(P0.00001),2033,2585,(19.8%),(25.2%),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,10
5、91,1390,(18.0%),(23.1%),否,(P0.00001),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%),100 130,10
6、83,1356,(21.6%),(26.9%),130,(P0.00001),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%)
7、,(32.3%),75,1666,2135,(21.6%),(27.6%),367,450,(14.4%),(17.7%),(P0.00001),2033,2585,(19.8%),(25.2%),0.4,0.6,0.8,1.0,1.2,1.4,基线特征,年龄 (岁),性别,男性,女性,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,HPS回答的主要问题:年龄/性别,Lancet 2002;360:7-22.,HPS: 为未来血脂研究引领方向,2002,PROVE IT A to Z 4D;SPARC
8、L ASPEN SALTIRE, SAGE,粥样斑块的影像学研究,HATS, FATS ILLUSTRATE,干预新的血脂治疗靶位,IDEAL TNT COURAGE,冠心病患者的治疗策略,ASTEROID METEOR BELLES,特殊患者人群的降脂治疗,20022007,冠心病和外周血管病 糖尿病 合并CHD 未合并CHD 高血压 中风病史 低胆固醇水平 老年 女性,10,HPS问世后的思考: 稳定性冠心病患者LDL-C治疗低限值?,CHD Risk (Log Scale),100,LDL-C (mg/dL),辛伐他汀 40 mg,60,26% Reduction in CVD,22%
9、Reduction in CVD,辛伐他汀 40 mg,Lancet 2002;360:7-22.,11,第一阶段 治疗后LDL-C:100mg/dL,30-40%降幅 标准剂量 v.s. 安慰剂,第二阶段 治疗后LDL-C:70mg/dL,50%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 heart disease. Cambridge, MA:
10、Harvard University Press, 1980; 381. Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994;308:367-72. Law MR. Lowering heart disease risk with cholesterol reduction: evidence from observational stu
11、dies and clinical trials. Eur Heart J Suppl 1999;(suppl S):S3-S8. Grundy SM, Wilhelmsen L, Rose G, Campbell RWF, Assmann G. Coronary heart disease in high-risk populations: lessons from Finland. Eur Heart J 1990;11:462-71. Peoples Republic of China-United States Cardiovascular and Cardiopulmonary Ep
12、idemiology Research Group. An epidemiological study of cardiovascular and cardiopulmonary disease risk factors in four populations in the Peoples Republic of China: baseline report from the P.R.C.-U.S.A. Collaborative Study. Circulation 1992;85:1083-96. Law MR, Thompson SG, Wald NJ. Assessing possib
13、le hazards of reducing serum cholesterol. BMJ 1994;308:373-9. Law MR, Wald NJ, Wu T, Hackshaw A, Bailey A. Systematic underestimation of association between serum cholesterol concentration and ischaemic heart disease in observational studies: data from the BUPA study. BMJ 1994;308:363-6.,13,稳定性冠心病他汀
14、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 1996; 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
15、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
16、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(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