稳定性心绞痛的调脂治疗

1、1HR 1.05*(0.87-1.27)P = 0.62Boden WE et al. N Engl J Med. 2007;356.总死亡率与心梗总死亡率与心梗*UnadjustedMedical therapy PCI + medical therapyNo. at riskMedical therapy1138101795983463840819230PCI1149101395283363741720035无事件无事件生存生存024700.81.00.9Years6531血脂目标血脂目标LDL-C:60-85mg/dl辛伐他汀依折麦布辛伐他汀依折麦布HDL-C:大于大于

2、40mg/dlTG:小于小于150mg/dl3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=0.000320015010050 0n=189n=111累积死亡人数安慰剂辛伐他汀P=0.00001Lancet 1994;344: 1383-89. Am J Cardiol 1995;76:64C-68C.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%P0.0000137%P0.00001Lancet 1994;344: 1383-89; Am J Cardiol 1995;76:64C-68C.对冠脉事件和心肌血管重建

3、术的影响对冠脉事件和心肌血管重建术的影响5Lancet 2002;360:7-22.9991250(23.5%)(29.4%)460591(18.9%)(24.2%)172212(18.7%)(23.6%)327420(24.7%)(30.5%)276367(13.8%)(18.6%)(P0.00001)20332585(19.8%)(25.2%)1.01.21.4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降低24% 危险性比值和危险性比值和 95%可信区间可信区间辛伐他汀辛伐他汀安慰剂安慰剂(10,269)(10,267)他

4、汀更好他汀更好安慰剂更好安慰剂更好6吸烟吸烟406531(15.7%)(20.6%)非常规吸烟者12981638(20.8%)(26.3%)戒烟者329416(22.8%)(28.4%)吸烟者治疗的高血压治疗的高血压9421195(22.4%)(28.1%)是10911390(18.0%)(23.1%)否(P0.00001)20332585(19.8%)(25.2%)所有患者所有患者主要血管事件主要血管事件1.01.21.4降低降低24%基线特征基线特征危险性比值和危险性比值和 95%可信区间可信区间辛伐他汀辛伐他汀安慰剂安慰剂(10,269)(10,267)他汀更好他汀更好

5、安慰剂更好安慰剂更好Lancet 2002;360:7-22.7LDL胆固醇胆固醇(mg/dl)282358(16.4%)(21.0%) 100668871(18.9%)(24.7%) 10021.6%)(26.9%) 130(P0.00001)20332585(19.8%)(25.2%)所有患者所有患者主要血管事件主要血管事件1.01.21.4降低降低24%入选时血脂水平入选时血脂水平危险性比值和危险性比值和 95%可信区间可信区间他汀更好他汀更好安慰剂更好安慰剂更好辛伐他汀辛伐他汀安慰剂安慰剂(10,269)(10,267)Lancet 2002

6、;360:7-22.88311091(16.9%)(22.1%) 65512665(20.9%)(27.2%)65 - 69548620(23.8%)(27.7%)70 - 74142209(23.1%)(32.3%) 7516662135(21.6%)(27.6%)367450(14.4%)(17.7%)(P50%降幅降幅大剂量大剂量 v.s. 标准剂量标准剂量Keys A, Arvanis C, Blackburn H. Seven countries:a multivariate analysis of death and coronary heartdisease. Cambridge

7、, MA: Harvard University Press,1980; 381.Law MR, Wald NJ, Thompson SG. By how muchand how quickly does 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 stud

8、ies andclinical 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-riskpopulations: lessons from Finland. Eur Heart J1990;11:462-71.Peoples Republic of China-United States Cardiovascularand Cardiopulmonary Epidemiolo

9、gy Research Group.An epidemiological study of cardiovascular andcardiopulmonary disease risk factors in 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 r

10、educing serum cholesterol. BMJ1994;308:373-9.Law MR, Wald NJ, Wu T, Hackshaw A, Bailey A.Systematic underestimation of association betweenserum cholesterol concentration and ischaemic heartdisease in observational studies: data from the BUPAstudy. BMJ 1994;308:363-6.13Lancet 1994: 344:1383-89; Lance

11、t 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每降低每降低1mmol/l LDL-C, 主主要冠脉事件风险降低要冠脉事件风险降低23%每降低每降低1mmol/l LDL-C，主，主要血管事件风险降低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相比安慰剂，通过中等剂量他汀治疗把LDL-C降低到降低到100mg/dL，降幅约，降幅约30%15Lancet 2005

12、; 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中等剂量他汀降低LDL-C治疗，可以治疗，可以显著降低冠心病死亡和主要血管事件显著降低冠心病死亡和主要血管事件的死亡。的死亡。16Lancet 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使用中等剂量他汀降低LDL-C治疗，不会治疗，不会增加非血管死亡和癌症发生率。增加非血管死亡和癌症发生率。1718Circulation 2004;110;227-239# 基线LDL-C100mg/dL

13、,药物治疗可选危险分层危险分层 LDL-C目标值目标值 启用启用 TLC 考虑药物治疗考虑药物治疗高度危险高度危险 100mg/dL#冠心病或其等危症冠心病或其等危症 可选可选:70mg/dL (20%) 考虑药物选用考虑药物选用)中度高危中度高危 130mg/dL 130mg/dL 130mg/dL2+ 危险因子危险因子 可选可选:100mg/dL (100-129mg/dL:(10年危险年危险10-20%) 考虑药物选用考虑药物选用)中度危险中度危险 130mg/dL 130mg/dL 160mg/dL2+ 危险因子危险因子(10年危险年危险 10%)低度危险低度危险 160mg/dL 1

14、60mg/dL 190mg/dL0-1 risk factor (160-189mg/dL: 考虑药物选用考虑药物选用)19*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 based on NCEP guidelines.Adapted from MRC/BHF Heart Pro

15、tection 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.基线基线*LDL-C (mg/dl)100 (2.6 mmol/L)100 130130 (3.4 mmol/L)

16、所有患者所有患者0.4 0.6 0.8 1.0 1.2 1.4Risk ratio and 95% CI Simvastatin Placebo betterbetterRRR24P=0.000130平均平均LDL-C水平水平(mg/dl)%主要血管事件主要血管事件6080100120140160辛伐他汀40mg安慰剂051015202526%22%21JAMA. 2005;294:2437-2445N Engl J Med 2005;352:1425-35.文献文献0.07-11%冠脉死亡，非致命心梗，心肺复苏8888Ato 80 v.s. Sim 20IDEAL(稳定性稳定性CHD)阿托伐

17、他阿托伐他汀汀/辛伐他辛伐他汀汀-22%相对相对风险风险下降下降60%的患者的患者经历了没有降脂治疗相同的血管事件。所以未来降脂治疗不是去寻找更强的他经历了没有降脂治疗相同的血管事件。所以未来降脂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，颗粒大小和斑块不稳定的其他机制。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-0524A2g按按1:1比例盲法活性药物治疗比例盲法活性药物治疗4年随访年随访 + 2300 主要血主要血管事件管事件周周随机化入组随机化入组 3个月随访个月随访 6个月随访个月随访 *患者在入组前的患者在入组前的12-16周