急性心肌梗死二级预防（学习资料）课件

冠心病二级预防,北京协和医院 朱文玲,Prevalence US including polyvascular patients (1.8M),时间发生 1 year,处于事件发生的危险中 (n=70 million),支架 急性心梗 急性冠脉综合症（ACS) 急性中风/短暂性脑缺血发作,曾经心梗 曾经中风 稳定性心绞痛 有症状的糖尿病 有症状的PAD 存有事件的房颤,无症状的PAD 无症状的糖尿病 存在其它危险因素,临床治疗的目标,提高生存率,预防事件再发,预防首次事件的发生,动脉粥样硬化血栓疾病的分级和总体的治疗目标,时间发生 1 year 曾经有事件 (n=15 million),急性/新近有事件 (n=3 million),血 管 事 件,危险因素,终末期（死 亡）,一级预防,二级预防,动脉粥样硬化血栓疾病的长期预防 的必要性,AMI二级预防,A aspirin 抗心绞痛 B B-B 高血压治疗 C 戒烟 血脂异常治疗 D 控制饮食 治疗糖尿病 E 病人教育 适当锻炼,AMI二级预防,非药物治疗 合理饮食 适当锻炼 戒烟 限酒 心理平衡,药物治疗 二级预防药物 控制冠心病危险因素 高血压 血脂异常 糖尿病,AMI二级预防药物治疗,B-B (B受体阻滞剂） AMI后用B-B明显降低MI后病残率和死亡率 早用，长期用,AMI二级预防药物治疗 B受体阻滞剂,AMI后二级预防B-B长期治疗建议 除低危患者外，所有无禁忌症者应在AMI发病数天内开始治疗，并长期服用 非ST段抬高的MI存活者及中重度左心衰竭或其他B-B相对禁忌症者可在密切监测下使用,ACC/AHA指南：AMI一般药物治疗的类建议（1999年版）,阿司匹林（无禁忌证者） 静脉使用硝酸甘油：伴有心衰、高血压或持续心肌缺血患者以及广泛前壁心梗患者 受体阻滞剂 ：12小时内开始使用（无禁忌证者） ACEI：伴有心衰或LVEF40%（无禁忌证者）,急性心肌梗死（AMI）,及早常规应用（无禁忌证） 减少心肌氧耗，缩小梗死面积，减轻胸痛，减少镇痛剂的使用 减少儿茶酚胺的细胞毒性和致心律失常作用；提高室颤阈 降低急性期的病死率、梗死后总死亡率、心血管病死亡率、猝死和再梗死的危险 最适合早期使用BB的是有高血流动力学状态的患者（如窦性心动过速、高血压） 用药方法与注意事项同高危UAP,BB治疗AMI的临床试验,BB治疗AMI的荟萃分析,引自Teo等,ESC指南：AMI二级预防 的类建议（2003年版）,BB 对心肌梗死的二级预防,BB是心肌梗死后二级预防的有效药物 降低心肌梗死后再梗率、猝死率、心脏死亡率和总死亡率 所有心肌梗死后的病人只要没有禁忌证都应长期使用 心肌梗死后高危患者如心功能减低者使用BB得益更明显 合并糖尿病宜用心脏选择性BB 溶栓治疗和血管成形术后的患者长期用BB获益,BB用于AMI二级预防的临床试验,AMI二级预防药物治疗 aspirin,大量研究证明 AMI后长期服用aspirin可以显著减少死亡率 长期服用aspirin者，发生MI时，梗死范围小，常为非Q波MI AMI无禁忌症者，都应长期服用aspirin 剂量 75-150mg/d 对aspirin过敏者用噻氯匹定 250mg/d或氯吡格雷75mg/d,17.1,6.5*,Placebo,ASA,0,5,10,15,20,Patients (%),Unstable Angina,25.0,11.0*,ASA,0,10,20,30,3.3,1.9*,ASA,0,1,2,3,4,11.8,9.4*,ASA,0,5,10,15,Acute MI,阿司匹林对ACS的治疗,*P.0001 Death or MI,*P=.003 Reocclusion,*P=.012 MI,*P.001 Death,N= 397 399 513 419 8587 8600 8587 8600,MI, myocardial infarction; ASA, acetylsalicylic acid; RISC, Research on InStability in Coronary artery disease. RISC Group. Lancet. 1990;336:827-830. Roux S, et al. J Am Coll Cardiol. 1992;19:671-677. ISIS-2. Lancet. 1988;2:349-360.,Placebo,Placebo,Placebo,阿司匹林对冠心病的一级和二级预防,12.9,3.9*,ASA,0,5,10,15,11.9,3.3*,ASA,0,5,10,15,12.9,6.2*,ASA,0,5,10,15,2.2,1.3*,ASA,0,0.5,1,1.5,2,2.5,UA/NSTEMI,Primary Prevention,Stable Angina,*P.0001 MI,*P=.0003 MI,*P=.008 Death or MI,*P=.012 Death or MI,N= 11034 11037 155 178 279 276 118 121,MI, myocardial infarction; ASA, acetylsalicylic acid; RISC, Research on InStability in Coronary artery disease; ISIS-2, Second International Study of Infarct Survival. PHS. N Engl J Med. 1989;321:129-35. Ridker PM, et al. AJC. 1991;114:835-839. Cairns JA, et al. N Engl J Med. 1985;313:1369-1375. Theroux P, et al. N Engl J Med. 1988;319:1105-1111.,Placebo,Placebo,Placebo,Placebo,Patients (%),阿司匹林的不同剂量,* Odds reduction. Treatment effect P.0001. ASA, acetylsalicylic acid. Adapted with permission from BMJ Publishing Group. Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86.,0.5,1.0,1.5,2.0,500-1500 mg 34 19,160-325 mg 19 26,75-150 mg 12 32,75 mg 3 13,Any aspirin 65 23,Antiplatelet Better,Antiplatelet Worse,Aspirin Dose No. of Trials (%),Odds Ratio,0,OR*,Clopidogrel in the treatment of ACS,plavix+ASA: ASA ACS患者持续服用氯吡格雷9-12个月能使缺血性事件相对危险降低达20 (p=0.00009),plavix+ASA: ASA 波立维的长期治疗（1年）可以显著地减少PCI病人的死亡，心梗和中风 (RRR 27%, p= 0.02),CAPRIE,CREDO,动脉粥样硬化疾病患者长期服用波立维1-3年比阿司林更能有效降低缺血性卒中、心肌梗死和血管性死亡的相对危险性达8.7%,plavix: ASA,2019/4/30,CAPRIE: 氯吡格雷 vs 阿司匹林 心梗，中风，血管性死亡 (N = 19,185),* ITT analysis. CAPRIE, Clopidogrel vs aspirin in Patients at Risk of Ischemic Events; MI, myocardial infarction; RRR, relative risk ratio. CAPRIE Steering Committee. Lancet. 1996;348:1329-1339. (with permission) Plavix (clopidogrel bisulfate) prescribing information.,Follow-up (mo),Cumulative Event Rate (%),0,4,8,12,16,Clopidogrel,Aspirin,Overall RRR2,8.7%*,0,3,6,9,12,15,18,21,24,27,30,33,36,Aspirin 5.83%1,5.32%1 Clopidogrel,P = .0452,Median Follow-up = 1.91 years,CURE, Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events; MI, myocardial infarction; CV, cardiovascular; RRR, relative risk reduction. Plavix package insert; 2002. Adapted with permission (2002) from the Massachusetts Medical Society. Yusuf S, et al. N Engl J Med. 2001;345:494-502.,CURE: Primary End Point 心梗/中风/血管性死亡,CREDO: PCI后一年结果,CV Death, MI or Stroke,* Plus ASA and other standard therapies . Steinhubl S, et al. JAMA. 2002;288:2411-2420. (with permission),Combined Endpoint Occurrence (%),Months From Randomization,27% RRR P=.02,Placebo* Clopidogrel*,0,5,10,15,8.5%,11.5%,0,3,6,9,12,Initial Medical Treatment （初始治疗）,ASA Betablockers LMWH,Clopidogrel,Planned CABG,Clopidogrel Withheld for 5 days Prefer 7 days,New ACC/AHA guidelines 2002:,Planned catheterisation and PCI,Early non interventional approach,ASA Betablockers LMWH,ASA Betablockers LMWH,Clopidogrel,Clopidogrel,GP b/a Receptor Inhibitor,ASA,Clopidogrel for 9 months,Beta-blockers,+,+,Lipid lowering therapy,+,ACE I,+,Class I Recommendations for Long Term Therapy*,ACC/AHA 2002 Guidelines Update for UA and NSTEMI（长期治疗）,1. Braunwald E et al. American College of Cardiology (ACC) and the American Heart Association (AHA) Guidelines, USA: ACC/AHA; 2002.,*At hospital discharge and post-hospital discharge In the absence of contraindications Clopidogrel should be administered to hospitalized patients who are unable to take ASA because of hypersensitivity or major GI intolerance,AMI二级预防药物治疗,调脂药,“中国血脂异常防治建议 ” 推荐的治疗目标值,CHD 状况 LDL-C目标 TC目标 动脉粥样硬化病(-)， 140 mg/dl 220 mg/dl 冠心病危险因子 (-) (3.64 mmol/L) (5.72 mmol/L) 动脉粥样硬化病(-)， 120 mg/dl 200 mg/dl 冠心病危险因子(+) (3.12 mmol/L) (5.20 mmol/L) 动脉粥样硬化病 (+) 100 mg/dl 180 mg/d (2.60 mmol/L) (4.68 mmol/L),中华心血管杂志 1997年6月第 25 卷第期。,TG目标值： 150 mg/dl (1.70 mmol/L),0,1,2,3,CHD RISK,100,160,220,LDL- cholesterol (mg/dL),* Men aged 50-70,85,65,45,25,HDL-C (mg/dL),FRAMINGHAM: CHD RISK OVER 4 YEARS,4S Study Group. Lancet. 1995;345:1274-1275 Sacks FM et al. N Engl J Med. 1996;335:1001-1009 LIPID Study Group. N Engl J Med 1998; 339:1349-1357,0,10,20,30,CARE-S,LIPID-S,4S-S,CARE-P,LIPID-P,4S-P,Statin Trials: LDL-C Levels vs Events Secondary Prevention,210 (5.4),90 (2.3),110 (2.8),130 (3.35),150 (3.9),170 (4.4),190 (4.9),LDL-C,S = statin treated P = placebo treated,% with CHD event,(mmol/L),mg/dL,临床试验,5年心梗发生率（%）,危险性,115,150,142,192,94,139,112,150,122,188,35,31,23,24,34,事件 %,终点 LDL,基础 LDL,无冠心病/一般胆固醇水平/低HDL胆固醇水平,冠心病,无冠心病高胆固醇水平,22.6,13.2/15.9,7.9,2.8,4S,CARE Lipid,WOSCOPS,AFCAPS/TexCAPS,4s(Lancet 94344:1383-89).CARE(1001-09), LIPID(NEJM 98:339:1349-57), AFCAPS(Tex Caps)(JAMA98:279:1615-22),WOSCOPS(NEJM95333:1301-07).,LDL 下降幅度（%）,35,25,32,26,23,冠心病高胆固醇水平,MIRACL Study Design,4 months,3073 patients,Atorvastatin 80 mg,Non-Q-wave infarction or unstable angina Randomised 2496 hours from admission Exclusions: Planned CABG/PTCA Prior Q-wave 7.1 mmol/L (270mg/dL),Patient population,Primary end point: Time to ischaemic events (CHD death, non-fatal MI, cardiac arrest, documented angina requiring hospitalisation),Usual care + double-blind placebo,MIRACL Results,Effects on LDL-C:,placebo group 124 mg/dl atorvastatin group 74 mg/dl,MIRACL Results,Effects on primary endpoint (death, non-fatal MI, cardiac arrest, recurrent ischemia requiring hospitalisation),placebo group 17.4% atorvastatin group 14.8% 16% reduction (p 0.05),MIRACL Results,Effects on stroke (secondary endpoint),placebo group 24% atorvastatin group 12% (p 0.05),MIRACL Conclusion,MIRACL provides convincing evidence of the benefits of commencing aggressive LDL lowering very early in patients with acute coronary syndromes,Background,Statin therapy is highly effective vs. placebo in long-term treatment of CHD Are statins effective in reducing events in patients with an acute coronary syndrome (ACS)? Does “intensive” LDL-C lowering to an average of 65 mg/dL achieve a greater reduction in clinical events than “standard” LDL-C lowering to an average of 95 mg/dL?,Cannon CP, Braunwald E, McCabe CH, et al. N Engl J Med 2004;350:15 ,PROVE-IT,4,162 patients with an Acute Coronary Syndrome,ASA + Standard Medical Therapy,“Standard Therapy” Pravastatin 40 mg,“Intensive Therapy” Atorvastatin 80 mg,Duration: Mean 2 year follow-up (925 events),Primary Endpoint: Death, MI, Documented UA requiring hospitalization, revascularization ( 30 days after randomization), or Stroke,PROVE-IT,Double-blind,Cannon CP, Braunwald E, McCabe CH, et al. N Engl J Med 2004;350:15 ,Patient Population,Hospitalization for acute MI or high-risk unstable angina Total cholesterol 240 mg/dL ( 200 mg/dL if on Lipid Rx) Stabilized (i.e., without ischemia, CHF, post PCI if performed),PROVE-IT,Cannon CP, Braunwald E, McCabe CH, et al. N Engl J Med 2004;350:15 ,Baseline Characteristics,Atorvastatin 80mg Pravastatin 40mg (2099) (2063) Mean Age (years) 58 58 Male/Female (%) 78 / 22 78 / 22 History of HTN (%) 51 49 Current Smoker (%) 36 37 History of Diabetes (%) 19 18 History of CHD (%) 37 39 STEMI / NSTEMI / UA (%) 36 / 36 / 29 33 / 37 / 30 Prior Statin Use (%) 26 25,PROVE-IT,Cannon CP, Braunwald E, McCabe CH, et al. N Engl J Med 2004;350:15 ,Changes in LDL-C from Baseline,LDL-C (mg/dL),20,40,60,80,100,120,Rand,1,4,8,16,Final,Pravastatin 40mg,Atorvastatin 80mg,49% ,21%,P0.001,Months,Screen,PROVE-IT,Cannon CP, Braunwald E, McCabe CH, et al. N Engl J Med 2004;350:15 ,All-Cause Death or Major CV Events,% with Event,Months of Follow-up,Pravastatin 40mg (26.3%),Atorvastatin 80mg (22.4%),16% RR (P = 0.005),30,25,20,15,10,5,0,PROVE-IT,Cannon CP, Braunwald E, McCabe CH, et al. N Engl J Med 2004;350:15 ,% with Event,0,3,18,21,24,27,30,6,9,12,15,20,15,10,5,0,Months of Follow-up,All-Cause Death, Non-Fatal MI, or Urgent Revascularization,Pravastatin 40mg 16.7%,Atorvastatin 80mg 12.9%,25% RR P = 0.0004,PROVE-IT,Cannon CP, Braunwald E, McCabe CH, et al. N Engl J Med 2004;350:15 ,PROVE-IT Conclusion,Our findings indicate that patients recently hospitalized for an acute coronary syndrome benefit from early and continued lowering of LDL-C to levels substantially below current target levels.,Cannon CP, Braunwald E, McCabe CH, et al. N Engl J Med 2004;350:15 ,其他治疗 (n=14,071),死亡率 (%)*,*Adjusted for 43 covariates Adapted from Stenestrand U, Wallentin L. JAMA. 2001;285:430-436.,注册后天数,400,300,200,100,0,5,4,3,2,1,5.0%,3.7%,瑞典注册研究:早期应用他汀类药 治疗改善AMI后生存率,RR 0.75 (95% CI, 0.63-0.89) P=.001,他汀治疗 (n=5,528),AMI二级预防血脂目标,TC 40mg/dl TG 150mg/dl,2004年7月12日Circulation发表的NCEP报告:新近的临床研究对NCEP ATPIII指南的影响,高危患者推荐的LDL-C目标100mg/dl 危险度很高时,将LDL-C的目标定为70mg/dl 高危及中等高危患者建议将LDL-C水平降低30%-40%,用什么药物进行治疗更好 （Which drug is better）,分类 TC LDLC TG HDLC 他汀类 20-40 20-60 10-50 5-10 贝特类 10-20 5-20 20-50 10-20 树脂类 15-30 15-30 5-8 3-5 烟酸类 15-25 15-30 5-8 3-5,用什么药物进行治疗更好 （Which drug is better）,ACE抑制剂,AMI二级预防治疗指南 年龄100mmHg者应长期服用ACEI 小剂量开始达到靶剂量或最大耐受剂量 （卡托普利150mg/d，依那普利40mg/d，雷米普利15mg/d，福辛普利10mg/d) 对MI面积小或下壁MI，无明显LV功能障碍者不推荐长期应用ACEI,ACEI降低心肌梗死死亡率研究,早期治疗 CONSENSUS II GISSI 3 ISIS 4 Chinese-Cap,高风险患者、长期治疗 SAVE (EF 40%) AIRE (临床心力衰竭) SMILE (前壁心肌梗死、未溶栓) TRACE (室壁运动评分,EF 35%),SAVE/AIRE/TRACE研究荟萃分析,年,安慰剂,Flather MD, et al. Lancet. 2000;355:15751581,OR: 0.74 (0.660.83),ACE-I: 702/2995 (23.4%),安慰剂: 866/2971 (29.1%),ACEI可以使高危心梗的总死亡率降低26%,总死亡率,ARBs: 用于心梗后的证据,OPTIMAAL OPtimal Trial In Myocardial infarction with the Angiotensin II Antagonist Losartan 血管紧张素II拮抗剂氯沙坦心肌梗死最佳试验,VALIANT VALsartan In Acute myocardial iNfarction Trial 缬沙坦急性心肌梗死试验,OPTIMAAL: 研究特征,目的 比较氯沙坦与卡托普利对高危心梗后患者的疗效 N=5,477; 随机分为: 卡托普利 50 mg tid 氯沙坦 50 mg qd 终点 主要终点: 所有原因死亡率 次级终点: 心源性猝死 或 复苏停搏 致死性及非致死性心梗 安全性与耐受性,OPTIMAAL: 所有原因死亡率,Dickstein K et al. Lancet 2002; 360:752-60.,氯沙坦,卡托普利,20,15,0,5,10,25,终点率,0 6 12 18 24 30 36,月,RR 1.13 95%CI 0.99-1.28 P=0.069,OPTIMAAL: 结论,本研究显示氯沙坦并不比卡托普利占优势，而且也未显示出其与卡托普利等效 根据 OPTIMAAL研究: - 对这组人群不推荐使用氯沙坦 - ACEI 仍是有并发症的急性心梗患者的一线治疗,主要终点: 总死亡率 次要终点: 心血管死亡、心肌梗死、心力衰竭 其他终点: 安全性和耐受性,卡托普利 50mg tid (n = 4909),缬沙坦 160mg bid (n = 4909),卡托普利 50mg tid + 缬沙坦 80mg bid (n = 4885),急性心肌梗死(0.510天)符合SAVE、AIRE或者TRACE研究的入选标准 (具备心力衰竭的临床/放射影象学证据和/或左室收缩功能障碍),随机、双盲、活性对照,平均随访时间:24.7月 事件驱动,VALIANT研究设计,Cap 6.25 mg Val 20 mg,Cap 12.5 mg Val 20 mg,Cap 25 mg Val 40 mg,Cap 50 mg (tid) Val 80 mg (bid),联合用药,Cap 6.25 mg,Cap 12.5 mg,Cap 25 mg,Cap 50 mg (tid),卡托普利 (tid) (Cap),Val 20 mg,Val 40 mg,Val 80 mg,Val 160 mg (bid),缬沙坦 (bid) (Val),步骤I,3个月达到目标剂量,步骤IV,步骤III,步骤II,将得到证实的ACEI有效剂量作为对照,Am Heart J. 2000;140:727734.,Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349,缬沙坦+卡托普利 VS. 卡托普利: 危险比 =0.98； P = 0.726,VALIANT研究主要终点：总死亡率,总死亡率,总死亡率非劣效性检验,0.8,1,1.2,危险比 (97.5%可信区间),1.13,P值 (非劣效性),0.002,方案治疗患者群体 (n = 14,285),0.004,意向治疗患者群体 (n = 14,703),非劣效性成立,缬沙坦优于卡托普利,卡托普利优于缬沙坦,非劣效性不成立,非劣效性 检验界值,非劣效性检验首次证实ARB与ACEI作用相当,代文可降低心肌梗死高危患者死亡率达25%,死亡率危险比,利于有效药物,利于安慰剂,Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349,三项研究的联合死亡率,缬沙坦可保 留卡托普利99.6%的生存利益,25%,心血管死亡、心梗或心衰的发生率,Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349,月,缬沙坦 VS. 卡托普利: 危险比 = 0.96； P = 0.198,缬沙坦+卡托普利 VS. 卡托普利: 危险比 = 0.97； P= 0.369,0,0.1,0.2,0.3,0.4,0,6,12,18,24,30,36,VALIANT研究次要终点,非劣效性成立,缬沙坦优于卡托普利,卡托普利优于缬沙坦,非劣效性不成立,缬沙坦降低心血管死亡和主要心血管事件危险 与ACEI相当,0.8,1,1.2,危险比 (97.5%可信区间),1.13,P值 (非劣效性),非劣效性 检验界值,心血管死亡率和并发症率,研 究 结 论,针对合并心力衰竭和/或左室功能障碍的心肌梗死患者: 缬沙坦与证实剂量的卡托普利可同样有效地降低下列事件的发生危险: 死亡 心血管死亡、非致死性心肌梗死、心衰住院 归因分析缬沙坦可降低心肌梗死高危患者死亡率达25% 缬沙坦与证实剂量的卡托普利联合用药未能进一步降低死亡率,同时可能增加不良反应。,临床意义: VALIANT研究首次证实，ARB(缬沙坦)对心肌梗死后高危患者的治疗作用与ACEI相当.降低心肌梗死高危患者死亡率达25%,钙结抗剂,不主张将CCB作为AMI的常规治疗和二级预防 对合并高血压，心绞痛，周围血管疾病的患者，如其他药物不能有效控制，可应用长效二氢吡定类或非二氢吡定类制剂 如受体阻滞剂禁忌可用维拉帕米或地尔硫卓替代，用于心功能正常患者,抗心律失常药物,MI后室性心律失常的大型临床试验表明I类抗心律失常药虽然抑制心律失常，但死亡率较安慰剂明显增加 负性肌力及致心律失常超过了抑制心律失常的作用 不能把抑制AMI后的心律失常作为治疗的最终目标,CAST-I,Echt DS. N. Engl J Med. 1991;324:781-788.,Prognosis of Post-MI Patients Treated with Placebo vs. Encainide/Flecainide,80,85,90,95,100,0,91,182,273,364,455,Days After Randomization,Patients Without Event (%),Placebo (n = 743),Encainide or Flecainide (n = 755),P = 0.001,CAST-II,CAST-II Investigators. N Engl J Med. 1992;327:227-233.,Moricizine,100,80,60,40,20,0,0,1,2,3,Year,Adjusted P = 0.40,Survival (%),Placebo,No. at risk (% surviving),Placebo Moricizine,574 (100) 581 (100),351 (95.2) 350 (94.9),175 (89.6) 181 (88.8),56 (88.0) 56 (85.0),Absence of Benefit of Moricizine Over Placebo,抗心律失常药物,EMIAT(The European myocardial infarction amiodarone trial) CAMIAT(Canadian amiodarone myocardial infarction arrhythmia trial) 胺碘酮可减少MI后室性心律失常 降低伴/不伴LV功能障碍患者的心律失常死亡和 心脏骤停 总死亡率无影响,EMIAT and CAMIAT Trials,1 Julian DG. Lancet. 1997;349:667-674. 2 Cairns JA. Lancet. 1997;349:675-682.,While amiodarone was effective in reducing arrhythmic death, it did not reduce total mortality.,SWORD Survival Results,Waldo AL. Lancet. 1996;348:7-12.,Patients at risk,Placebo