穩(wěn)定性心絞痛的調(diào)脂治療

1、1HR 1.05*(0.87-1.27)P = 0.62Boden WE et al. N Engl J Med. 2007;356.總死亡率與心?？偹劳雎逝c心梗*UnadjustedMedical therapy PCI + medical therapyNo. at riskMedical therapy1138101795983463840819230PCI1149101395283363741720035無事件無事件生存生存024700.81.00.9Years6531血脂目標血脂目標LDL-C:60-85mg/dl辛伐他汀依折麥布辛伐他汀依折麥布HDL-C:大于大于

2、40mg/dlTG:小于小于150mg/dl3辛伐他汀顯著降低所有原因的死亡率5.4年時，辛伐他汀顯著降低冠脈死亡的危險達42%30%P=0.000320015010050 0n=189n=111累積死亡人數(shù)安慰劑辛伐他汀P=0.00001Lancet 1994;344: 1383-89. Am J Cardiol 1995;76:64C-68C.4辛伐他汀顯著降低主要冠脈事件的危險辛伐他汀顯著降低心肌血管重建術(shù)的危險34%P0.0000137%P0.00001Lancet 1994;344: 1383-89; Am J Cardiol 1995;76:64C-68C.對冠脈事件和心肌血管重建

3、術(shù)的影響對冠脈事件和心肌血管重建術(shù)的影響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)無冠心病史腦血管疾病 外周血管疾病 糖尿病所有患者主要血管事件降低降低24% 危險性比值和危險性比值和 95%可信區(qū)間可信區(qū)間辛伐他汀辛伐他汀安慰劑安慰劑(10,269)(10,267)他

4、汀更好他汀更好安慰劑更好安慰劑更好6吸煙吸煙406531(15.7%)(20.6%)非常規(guī)吸煙者12981638(20.8%)(26.3%)戒煙者329416(22.8%)(28.4%)吸煙者治療的高血壓治療的高血壓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%基線特征基線特征危險性比值和危險性比值和 95%可信區(qū)間可信區(qū)間辛伐他汀辛伐他汀安慰劑安慰劑(10,269)(10,267)他汀更好他汀更好

5、安慰劑更好安慰劑更好Lancet 2002;360:7-22.7LDL膽固醇膽固醇(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%入選時血脂水平入選時血脂水平危險性比值和危險性比值和 95%可信區(qū)間可信區(qū)間他汀更好他汀更好安慰劑更好安慰劑更好辛伐他汀辛伐他汀安慰劑安慰劑(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%降幅降幅大劑量大劑量 v.s. 標準劑量標準劑量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, 主主要冠脈事件風(fēng)險降低要冠脈事件風(fēng)險降低23%每降低每降低1mmol/l LDL-C，主，主要血管事件風(fēng)險降低要血管事件風(fēng)險降低21%Lancet 2005; 366: 1267-78相比安慰劑，通過中等劑量他汀治療把相比安慰劑，通過中等劑量他汀治療把LDL-C降低到降低到100mg/dL，降幅約，降幅約30%15Lancet 2005

12、; 366: 1267-78每降低1mmol/L LDL-C對具體原因死亡的影響中等劑量他汀降低中等劑量他汀降低LDL-C治療，可以治療，可以顯著降低冠心病死亡和主要血管事件顯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對非血管死亡的影響每降低1mmol/L LDL-C對癌癥發(fā)生率的影響使用中等劑量他汀降低使用中等劑量他汀降低LDL-C治療，不會治療，不會增加非血管死亡和癌癥發(fā)生率。增加非血管死亡和癌癥發(fā)生率。1718Circulation 2004;110;227-239# 基線LDL-C100mg/dL

13、,藥物治療可選危險分層危險分層 LDL-C目標值目標值 啟用啟用 TLC 考慮藥物治療考慮藥物治療高度危險高度危險 100mg/dL#冠心病或其等危癥冠心病或其等危癥 可選可選:70mg/dL (20%) 考慮藥物選用考慮藥物選用)中度高危中度高危 130mg/dL 130mg/dL 130mg/dL2+ 危險因子危險因子 可選可選:100mg/dL (100-129mg/dL:(10年危險年危險10-20%) 考慮藥物選用考慮藥物選用)中度危險中度危險 130mg/dL 130mg/dL 160mg/dL2+ 危險因子危險因子(10年危險年危險 10%)低度危險低度危險 160mg/dL 1

14、60mg/dL 190mg/dL0-1 risk factor (160-189mg/dL: 考慮藥物選用考慮藥物選用)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.基線基線*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安慰劑051015202526%22%21JAMA. 2005;294:2437-2445N Engl J Med 2005;352:1425-35.文獻文獻0.07-11%冠脈死亡，非致命心梗，心肺復(fù)蘇8888Ato 80 v.s. Sim 20IDEAL(穩(wěn)定性穩(wěn)定性CHD)阿托伐

17、他阿托伐他汀汀/辛伐他辛伐他汀汀-22%相對相對風(fēng)險風(fēng)險下降下降60%的患者的患者經(jīng)歷了沒有降脂治療相同的血管事件。所以未來降脂治療不是去尋找更強的他經(jīng)歷了沒有降脂治療相同的血管事件。所以未來降脂治療不是去尋找更強的他汀和更大的劑量，而是與他汀的聯(lián)合治療，關(guān)注汀和更大的劑量，而是與他汀的聯(lián)合治療，關(guān)注HDL-C，TG，顆粒大小和斑塊，顆粒大小和斑塊不穩(wěn)定的其他機制。不穩(wěn)定的其他機制。Circulation.2006;113:1382-1384.*入選LDL-C:130-250mg/dL, 阿托伐他汀10mg 8周洗脫, LDL-C2.5 mmol/L (97 mg/dL) 1g MK-0524A2g按按1:1比例盲法活性藥物治療比例盲法活性藥物治療4年隨訪年隨訪 + 2300 主要血主要血管事件管事件周周隨機化入組隨機化入組 3個月隨訪個月隨訪 6個月隨訪個月隨訪 *患者在入組前的患者在入組前的12-16周