ACEI心衰治疗专题知识培训课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,ACEI心衰治疗专题知识,*,ACEI心衰治疗专题知识,ACEI心衰治疗专题知识,神经激素异常激活带来异常刺激后果,去甲肾上腺素,血管紧张素,肥厚，凋亡，缺血，心律失常，,心室重塑，纤维化,-,阻滞剂,ACE,抑制剂,ACEI心衰治疗专题知识,2,神经激素异常激活带来异常刺激后果去甲肾上腺素血管紧张素肥厚,循证医学证据：ACEI 治疗心力衰竭,试验,例数,心功能,治疗药物,随访,死亡率,P 值,CONSENSUS,253,IV,依那普利,6 m, 40%,0.002,V-HeFT II *,804,IIIII,依那普利,30 m, 28%,0.016,SOLVD-T,2569,IIIV,依那普利,41 m, 16%,0.0036,AIRE,2006,IIIII,雷米普利,15 m, 27%,0.002,AIREX,603,IIIII,雷米普利,59 m, 36%,0.002,*,与肼屈嗪-硝酸异山梨酯治疗相比较,ACEI心衰治疗专题知识,3,循证医学证据：ACEI 治疗心力衰竭试验例数心功能治疗药物随,ACEI治疗慢性心力衰竭/左室功能异常,前瞻性五大临床试验死亡率资料总结*,ACEI组,（n=6391）,对照组,（n=6372）,机会比,（95% CI）,P 值,6周,212 (3.3%),281 (4.4%),0.73 (0.61-0.88),0.0009,1年,724 (11.3%),828 (13.0%),0.85 (0.76-0.94),0.0028,2年,1038 (16.2%),1248 (19.6%),0.79 (0.72-0.86),0.0001,4年,1419 (22.2%),1659 (26.0%),0.80 (0.74-0.87),0.0001,总计,1467 (23.0%),1710 (26.8%),0.80 (0.74-0.87),225.2,mol/L,(,3mg/dl,),）,高血钾症（5.5 mmol/L）,低血压（SBP90 mmHg）,中华心血管病杂志,2002, 30(1):7-23,ACEI心衰治疗专题知识,8,ACE抑制剂心力衰竭应用要点（3） 中华医学会心血管病学分,氯沙坦心力衰竭试验（,ELITE-II）,假设和目的,假设,：在有症状心力衰竭患者中，与卡托普利相比，氯沙坦能更多地降低总死亡率（主要终点）、降低心脏猝死（包括复苏成功者）的发生率（第二终点）,如果上述假设得到证实，,氯沙坦将取代血管紧张素转换酶抑制剂作为治疗心力衰竭的标准,Pitt B, et al. J Card Fail 1999, 5(2):146-154,ACEI心衰治疗专题知识,9,氯沙坦心力衰竭试验（ELITE-II） 假设和目的假设：在,ELITE-II 试验：研究终点小结,卡托普利组,（n=1574）,氯沙坦组,（n=1578）,校正后危险比,（95% CI）,P 值,主要终点,总死亡率,250 (15.9%),280 (17.7%),0.88 (0.751.05),0.16,二级终点,猝死,/,复苏,115 (7.3%),142 (9.0%),0.80 (0.631.03),0.08,三级终点,总死亡,/,住院,707 (44.9%),752 (47.7%),0.94 (0.851.04),0.21,副作用停药,228 (14.5%),149 (9.4%),18,岁,;,EF18岁; EF40%ACE inhibitor treated/not treated,Primary outcome for Overall Programme: All-cause death,Primary outcome for each trial: CV death or CHF hospitalisation,ACEI心衰治疗专题知识,17,CHARM ProgrammeCHARM 相加组CHARM,CHARM-Alternative Trial,Median follow-up of 33.7 months,Candesartan,n=1013,Placebo,n=1015,Completed Study,n=1011,Completed Study,n=1014,Lost to follow-up,n=2,Lost to follow-up,n=1,2028 patients randomised,NYHA IIIV,LVEF ,40%,ACE inhibitor intolerant,ACEI心衰治疗专题知识,18,CHARM-Alternative TrialMedian,CHARM-Alternative: Primary outcome,心血管死亡和心衰住院率,Number at risk,Candesartan 1013 929 831 434 122,Placebo 1015 887 798 427 126,0,1,2,3,years,0,10,20,30,40,50,Placebo,Candesartan,%,HR 0.77 (95% CI 0.670.89), p=0.0004Adjusted HR 0.70, p0.0001,3.5,406 (40.0%,),334 (33.0%),ACEI心衰治疗专题知识,19,CHARM-Alternative: Primary out,CHARM-Added Trial,Median follow-up of 41 months,Candesartan,n=1276,Placebo,n=1272,Completed Study,n=1273,Completed Study,n=1271,Lost to follow-up,n=3,Lost to follow-up,n=1,2548 patients randomised,NYHA IIIV,LVEF ,40%,ACE inhibitor treated,ACEI心衰治疗专题知识,20,CHARM-Added TrialMedian follow,CHARM-Added:,Primary outcome,心血管死亡和心衰住院率,Number at risk,Candesartan 1276 1176 1063 948 457,Placebo 1272 1136 1013 906 422,0,1,2,3,years,0,10,20,30,40,50,Placebo,Candesartan,3.5,HR 0.85 (95% CI 0.750.96), p=0.011Adjusted HR 0.85, p=0.010,483 (37.9%),538 (42.3%),%,ACEI心衰治疗专题知识,21,CHARM-Added: Primary outcome心,CHARM,试验的临床意义,ARB用于慢性收缩性心力衰竭患者是有效的,康得沙坦显著降低心血管病死亡和病残联合终点事件发生率,总死亡率未能显著降低，提示疗效不如ACE抑制剂,ARB作为心力衰竭治疗二线药物（替代）的地位得到确立,ARB和ACE抑制剂合用有相加的效益,康得沙坦显著降低心血管病死亡和病残联合终点事件发生率,ARB、ACE抑制剂和,-阻滞剂三药合用可能是安全的,已用ACE抑制剂和,-阻滞剂的患者是否加ARB，仍需研究,ACEI心衰治疗专题知识,22,CHARM试验的临床意义ARB用于慢性收缩性心力衰竭患者是有,Standard post-AMI care,ASA, BB, ACEI, statin, revascularization,急性心肌梗死后(314 d), LVEF 40, rales or S3,Randomization,(n=6642),Eplerenone initiation (n=3319),25 mg qd, 50 mg at 4 wk,Matching placebo,(n=3313),Follow-up (16 month),依普利酮急性心肌梗死后心力衰竭的效益和生存研究（EPHESUS）,Pitt B, et al. N Engl J med 2003;348(14):13091321,ACEI心衰治疗专题知识,23,Standard post-AMI care急性心肌梗死后(,EPHESUS：主要终点事件,0.002,0.87,(0.79-0.95),993,885,心血管病死亡或住院,0.008,0.85,(0.75-0.96),554,478,死亡,P 值,相对危险,(95% CI),安慰剂 (N=3313),依普利酮(N=3319),Pitt B, et al. N Engl J med 2003; 348(14):13091321,ACEI心衰治疗专题知识,24,EPHESUS：主要终点事件 0.0020.87 99388,ACE抑制剂治疗心力衰竭新动态,ACE抑制剂是治疗慢性心力衰竭的基石和首选药物,慢性收缩性心力衰竭的标准治疗，就是ACE抑制剂单用或加用利尿剂，心功能 级的患者加用,-受体阻滞剂，地高辛可合用也可不用。,能耐受ACE抑制剂的患者不宜用ARB取代,醛固酮拮抗剂有望成为第三类神经激素拮抗药,ACEI心衰治疗专题知识,25,ACE抑制剂治疗心力衰竭新动态ACE抑制剂是治疗慢性心力衰竭,Evidences from systematic overview of trials on early ACEI after Myocardial Infarction,ACE Inhibitor Myocardial Infarction Collaborative Group,Circulation 1998; 97: 22022212,ACEI心衰治疗专题知识,26,Evidences from systematic over,ACEI心衰治疗专题知识,27,ACEI心衰治疗专题知识27,ACEI心衰治疗专题知识,28,ACEI心衰治疗专题知识28,Effect of ACE-inhibitor therapy on cumulative mortality during days 0 to 30,ACEI心衰治疗专题知识,29,Effect of ACE-inhibitor therap,AMI,早期,ACE,抑制剂降低死亡率的绝对效益,（,非选择性患者，,n=98 496）,0,1000,2000,3000,4000,Number of deaths,01 days,27 days,830 days,Total,Control,ACE-I,104,39,239,96,Lives saved per 1000,0.9,4.8,95%CI,-1.0 2.9,1.5 8.0,2.2,0.0 4.4,1.9,0.3 3.6,ACEI心衰治疗专题知识,30,AMI早期ACE抑制剂降低死亡率的绝对效益010002000,卡托普利早期应用对心肌梗死患者远期病死率的影响：中国心脏研究-远期随访报告,CCS-1入选的AMI（发病36h内）患者,卡托普利（12.5mg，3次/d）或安慰剂治疗 4 周,随访,7079例,：平均随访23.316.9月（192个月）,与安慰剂组（n=3525）相比，卡托普利组（n=3554）,累计,总死亡率,降低10.6%（16.0%:17.9%, p=0.03）,累计,心血管病死亡率,降低11.4% （14.7%:16.6%, p=0.03）,累计,心力衰竭死亡率,降低25.0% （4.5%:6.0%, p=0.004）,结论：AMI 患者早期接受卡托普利治疗4周，能显著降低长期死亡率（每治疗1000例，2 年中累计可救命19人）,ACEI心衰治疗专题知识,31,卡托普利早期应用对心肌梗死患者远期病死率的影响：中国心脏研究,CCS-1：早期与远期病死率（%）,死亡原因,早期死亡率,死亡减少,远期死亡率,死亡减少,对照组,治疗组,1000人,对照组,治疗组,1000人,总病死率,9.6,9.0,6,8.3,7.0 *,13,心血管病,9.5,8.8,7,7.2,5.9,13,心力衰竭,2.5,1.9,6,3.6,2.6 *,10,猝死,0.2,0.3,-1,1.5,1.3,2,脑出血,0.8,0.6,2,0.4,0.3,1,非心血管病,0.2,0.1,1,0.9,0.9,0,与安慰剂组比较，*,p=0.05, *,p=0.02,ACEI心衰治疗专题知识,32,CCS-1：早期与远期病死率（%）死亡原因早期死亡率死亡减少,ACEI心衰治疗专题知识培训课件,Evidence from early and late trials overviews,Early approach of an unselected population of AMI patients, 5 lives saved per 1000p=0.004, 6 nonfatal CHF per 1000p=0.01,followed by a,Late treatment of the patients with LV dysfunction/heart failure, 44 lives saved per 1000p0.0001, 20 reAMI saved per 1000p=0.0004,心肌梗死后,A,CE,抑制剂效益汇总分析,ACEI心衰治疗专题知识,34,Evidence from early and late t,UA & NSTEMI,治疗指南：新特点,（ACC/AHA，2002 update）,急性期：在伴有左室收缩功能异常的AMI或新近有过MI的患者中，在左室功能异常的糖尿病患者中，在各种高危慢性冠心病患者中，,包括左室功能正常的患者,，ACE抑制剂都能降低死亡率。因此，在所有这些患者中，以及用,-,阻滞剂和硝酸盐未能控制的高血压患者中，都应该使用ACE抑制剂。,长期用：有心力衰竭、左室功能异常(LVEF,40%,)、高血压或糖尿病的患者（,A级,证据水平）,ACEI心衰治疗专题知识,35,UA & NSTEMI 治疗指南：新特点（ACC/AHA，,Heart Outcomes Prevention Evaluation Study,A large randomized trial of Ramipril and vitamin E in patients at high risk for cardiovascular events,ACEI心衰治疗专题知识,36,Heart Outcomes Prevention Eval,HOPE,：主要终点发生率及总死亡率,心肌梗死/中风/心血管病死亡,心血管病死亡,*,心肌梗死,*,中风,*,非心血管病死亡,总死亡率(任何原因),14.0 17.8 0.78 0.70- 0.86 0.001,6.1 8.1 0.74 0.64- 0.87 0.001,9.9 12.3 0.80 0.70- 0.90 0.001,3.4 4.9 0.68 0.56- 0.84 18,岁（,n=12 218）,有冠心病客观证据,既往心肌梗死, 3,个月,PCI / CABG 6,个月,冠状动脉造影证据,（,狭窄,70%,）,男性胸痛患者：运动试验或负荷试验阳性,没有冠状动脉介入治疗或搭桥手术的计划,没有心力衰竭的临床表现,ACEI心衰治疗专题知识,39,EUROPA: Selection criteria 男性,%,CV death, MI or cardiac arrest,Placebo annual event rate: 2.4%,Perindopril,Placebo,p = 0.0003,RRR: 20%,Years（,平均随访4.2年,）,0,2,4,6,8,10,12,14,0,1,2,3,4,5,EUROPA: Primary endpoint,ACEI心衰治疗专题知识,40,% CV death, MI or cardiac arre,EUROPA：Summary of results,培哚普利（8mg qd）治疗50例冠心病患者4年，能预防1例心血管病死亡、非致死心肌梗死或心脏骤停,在一个有60 000 000人口的国家，采用培哚普利治疗冠心病患者4年，能预防50 000例心肌梗死或心血管病死亡,效益在其他最佳治疗（抗血小板药、调脂药、,-,阻滞剂）基础上取得，各亚组中有一致的效益,培哚普利应该用作所有冠心病患者的长期治疗,Fox KM, et al. Lancet 2003, 362(9386): 782788,ACEI心衰治疗专题知识,41,EUROPA：Summary of results培哚普利（,老年冠心病患者的二级预防,（AHA指南 2002-01）,所有发生心肌梗死的患者都应该接受,ACE抑制剂,治疗，病情稳定的高危患者应早期开始治疗。,所有冠心病或其他血管疾病的患者都应该考虑,ACE抑制剂,治疗，除非有禁忌证。,ACEI心衰治疗专题知识,42,老年冠心病患者的二级预防（AHA指南 2002-01）所,心肌梗死后使用血管紧张素II受体拮抗剂氯沙坦最佳试验,（OPTIMAAL）,第一项在急性心肌梗死后患者中直接比较ACE抑制剂和ARB治疗对死亡率影响的大规模临床试验,5477例,50岁,急性心肌梗死后的高危患者,急性期有心力衰竭症状或体征,左室功能异常（LVEF65mm）,新发生有Q波前壁心肌梗死、或前壁导联原有异常Q波患者发生再次心肌梗死,卡托普利（50mg tid）,vs,氯沙坦（50mg qd）,Dickstein K, et al. Lancet 2002,ACEI心衰治疗专题知识,43,心肌梗死后使用血管紧张素II受体拮抗剂氯沙坦最佳试验（OPT,OPTIMAAL:,试验终点发生率比较,氯沙坦（n=2744）,卡托普利（n=2733）,相对危险（95% CI）,P 值,总死亡率,499 (18.2%),447 (16.4%),1.13 (0.991.28),0.069,心猝死复苏,239 (8.7%),203 (7.4%),1.19 (0.991.43),0.072,再次心肌梗死,384 (14.0%),379 (13.9%),1.03 (0.891.18),0.722,心血管病死亡,420 (15.3%),363 (13.3%),1.17 (1.011.34),0.032,中风,140 (5.1%),132 (4.8%),1.07 (0.841.36),0.587,Dickstein K, et al. Lancet 2002,ACEI心衰治疗专题知识,44,OPTIMAAL: 试验终点发生率比较氯沙坦（n=2744,Pfeffer MA, et al. N Engl J Med 2003, 349(20):18931906,Supported by a grant from Novartis Pharmaceuticals,Marc A. Pfeffer, MD, PhD (Chair), John J.V. McMurray, MD (Co-Chair), Eric J. Velazquez, MD, Jean-Lucien Rouleau, MD, Lars Kber, MD, Aldo P. Maggioni, MD, Scott D. Solomon, MD, Karl Swedberg, MD, PhD, Frans Van de Werf, MD, PhD, Harvey D. White, DSc, Jeffrey D. Leimberger, PhD, Marc Henis, MD, Susan Edwards, MS, Steven Zelenkofske, DO, Mary Ann Sellers, MSN, and Robert M. Califf, MD, for the VALIANT Investigators,VAL,sartan,I,n,A,cute,myocardial,i,N,farc,T,ion,Other Steering Committee Members: P. Armstrong, P. Aylward, S. Barvik, Y. Belenkov, A. Dalby, R. Diaz, H. Drexler, G. Ertl, G. Francis, J. Hampton, A. Harsanyi, J. Kvasnicka, V. Mareev, J. Marin-Neto, J. Murin, M. Myers, R. Nordlander, G. Opolski, J. Soler-Soler, J. Spac, T. Stefenelli, D. Sugrue, W. Van Gilst, S. Varshavsky, D. Weaver, F. Zannad.,ACEI心衰治疗专题知识,45,Pfeffer MA, et al. N Engl J M,Captopril,(4909),50mg tid,4871 (99.2%),Vital status unknown:,38 (0.8%),VALIANT: Enrollment and Follow-up,Median follow-up: 24.7 months,Valsartan,(4909),160mg bid,4856 (98.9%),Vital status unknown:,53 (1.1%),14 808 Patients Randomized,4837 (99.0%),Vital status unknown:,48 (1.0%),Combination,(4885),50mg bid + 80mg bid,Informed consent,not ensured: 105 patients,Vital status ascertained in 14 564 patients (99.05%),Vital status not ascertained in 139 patients (0.95%),14 703 Patients,ACEI心衰治疗专题知识,46,Captopril (4909)4871 (99.2%)Vi,VALIANT: Mortality by Treatment,Valsartan 4909 4464 4272 4007 2648 1437 357,Captopril 4909 4428 4241 4018 2635 1432 364,Valsartan+Cap 4885 4414 4265 3994 2648 1435 382,Captopril,0,0.05,0.1,0.15,0.2,0.25,0.3,0,6,12,18,24,30,36,Probability of Event,Months,Valsartan vs. Captopril: HR = 1.00; P = 0.982,Valsartan + Captopril vs. Captopril: HR = 0.98; P = 0.726,Valsartan,Valsartan + Captopril,ACEI心衰治疗专题知识,47,VALIANT: Mortality by Treatmen,VALIANT: Adverse Experience Leading to Study Drug Discontinuation,*,*,*,*,Valsartan,Valsartan + Captopril,Captopril,Hypotension Renal Hyperkalemia Cough Skin Taste Angioedema,Causes Rash Disturbance,* P 0.05 Valsartan vs. Captopril,P 0.05 Valsartan + Captopril vs. Captopril,0,0.5,1,1.5,2,2.5,3,3.5,% of Patients,ACEI心衰治疗专题知识,48,VALIANT: Adverse Experience L,VALIANT:,Conclusion,In ptients with MI complicated by heart failure, left,ventricular dysfunction or both:,Valsartan is as effective as a proven dose of captopril in reducing the risk of:,Death,CV death or nonfatal MI or heart failure admission,In these patients, valsartan is a clinically effective alternative to an ACE inhibitor,Combining valsartan with captopril produced no further reduction in mortalityand more adverse drug events,ACEI心衰治疗专题知识,49,VALIANT: ConclusionIn ptients,ACE,抑制剂治疗心肌梗死新动态,绝大多数急性心肌梗死患者需要ACE抑制剂治疗,绝大多数心肌梗死后的患者需要ACE抑制剂治疗,绝大多数冠心病患者需要ACE抑制剂治疗,在心肌梗死后患者中，大剂量ARB降低死亡率的效果与常规剂量ACE抑制剂相似，但副作用发生率显著增高,在心肌梗死后患者中，ARB与ACE抑制剂可能不宜合用,ACEI心衰治疗专题知识,50,ACE抑制剂治疗心肌梗死新动态绝大多数急性心肌梗死患者需要A,