冠心病的二级预防王建安

冠心病的二级预防,浙江大学医学院附属第二医院 心脏中心 王建安 项美香,动脉粥样硬化血栓形成*是目前世界上导致死亡的主要原因1,28.7,17.8,12.6,9.1,6,5.1,0,5,10,15,20,25,30,动脉粥样硬化血栓形成*,感染和寄生虫性疾病,癌症,创伤,肺疾病,AIDS,1. 世界卫生报告, 2002, WHO Geneva, 2002.,死亡率(%),*缺血性心脏病、脑血管病、感染性心脏病和高血压性心脏病; WHO各成员国通过的世界性的定义 (非洲、美洲、中东、欧洲、东南亚和西太平洋),*Sudden death defined as death documented within 1 hour and attributed to coronary heart disease (CHD); Includes only fatal MI and other CHD death; does not include non-fatal MI 1. Kannel WB. J Cardiovasc Risk 1994; 1: 333339. 2. Wilterdink JI, Easton JD. Arch Neurol 1992; 49: 857863. 3. Adult Treatment Panel II. Circulation 1994; 89:13331363. 4. Criqui MH et al. N Engl J Med 1992; 326: 381386.,23倍2,与普通人群相比风险增高,心肌梗死,卒中,57倍3,34倍1,23 倍,9倍2,4倍（仅包括致死性心梗和其他冠心病死亡）4,缺血性卒中,心肌梗死,外周动脉疾病,即使从第一次事件中幸存下来 患者仍处于再发事件的高风险中,冠心病的预防性治疗,一级预防 二级预防 对象 已有危险因 已发生冠心 素、但尚未 病者 发生冠心病 方法 积极控制危 针对发病机 险因素 制进行治疗 目的 减少发病机 降低死亡率/ 会、延缓发 病残率、提 病时间 高生活质量,冠心病的二级预防,AAspirin and ACEI/ARB BBeta blockers and Blood Pressure control CCholesterol and Cigarettes DDiet and Diabetes EEducation and Exercise,二级预防的药物治疗的益处,Risk Reduction,抗血小板治疗,动脉粥样硬化血栓形成（AT）： 动脉粥样硬化（AS）斑块上形成的血栓,Adapted from Falk E, et al. Circulation. 1995;92:657-671.,血小板,激活,TXA2,活化的 血小板,COX,脱颗粒,凝血酶 5-羟色胺 肾上腺素 胶原蛋白,Gp IIb/IIIa 纤维蛋白原 受体,达邻近 血小板,Gp IIb/IIIa 抑制剂,Mehta SR. J Am Coll Cardiol.,抗血小板药物的作用,抗血栓协作组荟萃分析* 抗血小板治疗对各心脑血管患者亚组均有降低心血管事件的作用,* 包括心肌梗死（MI）脑血管意外（CVA），血管性死亡,BMJ 2002;324:71-86,20,10,0,既往MI,急性MI,急性CVA,既往CVA/TIA,其他高风险,全部,13.5,17,10.4,14.2,17.8,8.2,21.4,9.1,8,10.2,10.7,13.2,抗血小板 对照,心血管事件* %,P0.0001,P0.0001,P0.0001,P0.0001,P0.0001,P0.0001,* 涵盖了至97年9月的所有临床研究（n=135,000, 287项随机对照试验）,抗血小板治疗的有效性,Wallentin LC et al JACC 1991;18:15871593,UAP患者长期服用阿司匹林减少死亡和MI的疗效,AHA/ACC Guideline,Start aspirin 75 to 162 mg/d and continue indefinitely in all patients unless contraindicated. I (A) For patients undergoing coronary artery bypass grafting, aspirin should be started within 48 hours after surgery to reduce saphenous vein graft closure. Dosing regimens ranging from 100 to 325mg/d appear to be efficacious. Doses higher than 162 mg/d can be continued for up to 1 year. I (B),Circulation 2006;113;2363-2372,阿司匹林+氯吡格雷使ACS、PCI患者获益增加,血管紧张素转换酶抑制剂 在二级预防中的作用,肾小球滤过率 蛋白尿 醛固酮释放 肾小球硬化,AII 在器官损害过程中扮演核心角色,Adapted from Willenheimer R et al Eur Heart J 1999; 20(14): 9971008, Dahlf B J Hum Hypertens 1995; 9(suppl 5): S37S44, Daugherty A et al J Clin Invest 2000; 105(11): 16051612, Fyhrquist F et al J Hum Hypertens 1995; 9(suppl 5): S19S24, Booz GW, Baker KM Heart Fail Rev 1998; 3: 125130, Beers MH, Berkow R, eds. The Merck Manual of Diagnosis and Therapy. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories 1999: 16821704, Anderson S Exp Nephrol 1996; 4(suppl 1): 3440, Fogo AB Am J Kidney Dis 2000; 35(2): 179188,A II AT1 受体,动脉粥样硬化* 血管收缩 血管增厚 内皮功能紊乱,左心室肥厚 纤维化 重构 细胞凋亡,中风,死亡,*preclinical data,高血压,心肌梗塞 心衰,肾衰,ACEI,A I,患者人群 各种心血管病:80.6% 既往心梗:52.8% 稳定性心绞痛:54.9% 既往 CABG:25.6% 既往 PTCA:17.9% 卒中/TIA:10.8% 外周血管病/肢体血压异常:43.4% ECG显示左室肥厚: 8.4% 糖尿病合并一种CVD危险因素:38.4% 高血压 总胆固醇 5.2 mmol/L HDL 胆固醇 0.9 mmol/L 微量白蛋白尿 抽烟者,80%,HOPE研究Heart Outcomes Prevention Evaluation,HOPE-雷米普利10mg vs 安慰剂,N Engl J Med 2000; 342: 145-153,联合终点: 心肌梗死，中风和心血管死亡,Risk reduction = 22%,0.00,0.05,0.10,0.15,0.20,0,500,1000,Days of Follow-up,p0.001,P,r,o,p,o,r,t,i,o,n,o,f,P,a,t,i,e,n,t,s,1500,Ramipril,Placebo,HOPE 研究： 雷米普利10mg降低高危患者心血管危险的作用，超越了降压作用之外,HOPE研究结论,对于高危CVD病人 雷米普利治疗4.5年能显著降低： 心肌梗死、卒中和心血管死亡的发生率 心力衰竭，血管重建术（CABG/PTCA）的发生率 减少新发糖尿病 使用雷米普利治疗高危患者的益处是持续的 仅观察到较安慰剂高5%的咳嗽发生率 维生素E对于心血管事件的作用是中性的,HOPE、EUROPA、PEACE比较 *,N Engl J Med. 2005;352:937-939,HOPE Study Investigators. N Engl J Med. 2000;342:145-53. EUROPA Investigators. Lancet. 2003;362:782-8. PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.,HOPE、EUROPA、PEACE比较,PEACE,ACC/AHA 2002 指南,I 类 ACEI用于所有的冠心病患者 (同时伴糖尿病和/或左室功能不全) (证据水平: A) IIa 类 对冠心病或其他血管疾病患者使用ACEI(证据水平: B),他汀类降脂药,LDL-C Is Closely Related to CHD Events1,1. Adapted from Ballantyne CM. Low-density lipoproteins and risk for coronary artery disease. Am J Cardiol. 1998;82:3Q12Q, with permission from Excerpta Medica. 2. Heart Protection Study Collaborative Group. Lancet. 2002;360:722.,Mean On-Treatment LDL-C Level at Follow-Up (mg/dL),4S,CARE,LIPID,HPS2,AFCAPS,WOSCOPS,WOSCOPS,2 Prevention,1 Prevention,CHD + Revasc + Stroke (HPS = CHD Only)Solid Shapes = Drug RxOutline Shapes = Placebo,CHD Events, %,What is the evidence for LDL-C target in high risk patient?,%,*,*,*Confidence interval (CI) not reported. 95% CI, 14%-41%. 95% CI, 16%-37%. 95% CI, 12%-31%.,Hebert PR et al. JAMA. 1997;278:313-321.,Impact of Lowering LDL-C on CVD Events and Total Mortality,Nonfatal/fatal CHD,CVDmortality,他汀用于二级预防，显著降低事件,Scandinavian Simvastatin Survival Study Group. Lancet. 1994;344:1383-1389; Lewis SJ et al. Ann Intern Med. 1998;129:681689; LIPID Study Group. N Engl J Med. 1998;339:1349-1357; HPS Collaborative Group. Lancet. 2002;360:7-22; Athyros VG et al. Curr Med Res Opin. 2002;18:220-228; Koren MJ et al. J Am Coll Cardiol. 2004; 44:1772-1779.,*In all trials apart from GREACE and ALLIANCE. Subgroup with prior CHD. Primary end points: 4S=total mortality; CARE=5-year event rates of major coronary events (coronary death, nonfatal MI, angioplasty, or bypass surgery) and stroke; LIPID=CHD mortality; HPS=mortality and fatal and nonfatal vascular events; GREACE=death, nonfatal MI, unstable angina, congestive heart failure, revascularization, and stroke; ALLIANCE=time to first cardiac event.,他汀显著降低ACS患者的事件,Schwartz GG et al. JAMA. 2001;285:1711-1718; Cannon CP et al. N Engl J Med. 2004;350:1495-1504; de Lemos JA et al. JAMA.2004;292:1307-1316.,*Statin dose vs placebo. Primary end points: MIRACL=death, nonfatal acute MI, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization; PROVE IT=time from randomization to first occurrence of: death from any cause, MI, documented unstable angina requiring rehospitalization, revascularization with either percutaneous coronary intervention or coronary-artery bypass grafting, and stroke; A to Z=composite of CV death, nonfatal MI, readmission for ACS, and stroke.,Is Lower Better?,Is Lower Better? HPS,冠心病风险对数值,100,LDL-C (mg/dL),辛伐他汀40 mg,60,心血管事件减少26%,心血管事件减少22%,辛伐他汀40 mg,Heart Protection Study Collaborative Group. Lancet 2002;360:722.,“越低越好”,冠心病相对风险 (对数值),3.7,2.9,2.2,1.7,1.3,1.0,LDL-C (mg/dL),40,70,100,130,160,190,0,1,Grundy SM et al. Circulation 2004;110:227239.,Changes to NCEP ATP III LDL-C Goals,NCEP=National Cholesterol Education Program; ATP III=Adult Treatment Panel III Adapted from Grundy SM et al Circulation 2004;110:227239; Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults JAMA 2001;285:24862497.,2007中国成人血脂指南高脂血症患者开始治疗标准值及治疗目标值,*极高危病人缺血性心血管疾病(CHD)+ 1)急性冠脉综合征 2)糖尿病,总 结,健康的生活方式 危险因素的控制 合理药物治疗 遵循指南治疗达标,谢谢,