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1、正确评价-受体阻滞剂在高血压治疗中 一线药物的地位华中科技大学同济医学院协和医院心血管病研究所戴闺柱,SNS 在心血管疾病的重要性 高血压早期已有SNS激活-受体阻滞剂具有证据确鑿的 心脏保护作用-受体阻滞剂的临床实践,Medalie JH,et al.J Chronic Dis,以色列公务员研究：心率与心肌梗死危险,Framingham：心率与死亡率,Gillman MW,et al.Am Heart J 1993;125:1148-1154,Adjusted survival curves for overall mortality by RHR quintiles,Cumulative
2、survival,RHR in quintilies,-83 bpm,1.0,0.9,0.8,0.7,0.6,0.5,0.00,5.00,10.00,15.00,20.00,Years after enrolment,Figure 1 adjusted for age,gender,hypertension,diabetes mellitus,cigarette smoking,clinically significant coronary vessel,EF,recreational activity,treatment with antiplatelets,diuretics,b-bloc
3、kers,and lipid-lowering drugs.RHR,resting heart rate.,n=24,913FU 14.7 years,Ariel Diaz et al.EHJ 2005,reference 1.06(0.97-1.17)1.09(0.98-1.21)1.16(1.04-1.28)1.32(1.19-1.47)(p-value0.0001),Cumulative survival,RHR in quintilies,-83 bpm,1.0,0.9,0.8,0.7,0.6,0.5,0.00,5.00,10.00,15.00,20.00,Years after en
4、rolment,Adjusted survival curves for CV mortality by RHR,Figure 2 Asterisk indicates adjusted as Figure 1 plus BMI.CV,cardiovas-cular;RHR,resting heart rate.,n=24,913FU 14.7 years,Ariel Diaz et al.EHJ 2005,reference 1.05(0.97-1.17)1.07(0.98-1.21)1.14(1.04-1.28)1.31(1.19-1.47)(p-value0.0001),静息心率冠心病病
5、残率、死亡率的强预测因素,静息心率增快与心血管病死率和病残率呈前瞻 性正相关,独立于动脉粥样硬化其他危险因素 静息心率80-85bpm是正常和异常心率的分割水平 心率80bpm被证实易于使冠状动脉斑快破裂-阻滞剂有保护作用 大量证据证明心动过速不仅是其他心血管危险 因素的一个“marker”，而且可导致额外的心血 管系统的损害 应将静息心率作为心血管病人危险因素分层的 参数，预防性治疗可使病人获得更大的益处。,Paolo Palatini.European Heart Journal(2005)26,943-945,心理社会应激为触发因素,猝死,应激事件 防御反应,导致迷走抑制 2.增加交感张
6、力(中枢神经系统、心脏),b1,增加猝死发生的危险性,降低心脏电稳定性,心率 收缩力 收缩压 缺血发生,Wikstrand 17:165A,January 1994,Leor et al,NEJM 1996,0,10,20,30,Number of Sudden Deaths,11,14,17,20,23,The Northridge EarthquakeJanuary 17,1994,at 4.31 am,Relative Risk 5.2(p0.001),Psychosocial Stress and the Triggering of Sudden Death,-阻滞剂的作用机制,降低交
7、感神经张力 防止儿茶酚胺的心脏毒性作用 抑制异常、过度、持续的神经激素活性增高 和 RAS 间的相互作用:降低血压 缓解心肌缺血(减少心肌耗氧、冠脉血流有利的重分配）改善心肌重构 减慢心率 减少心律失常（包括复杂室性心律失常）提高心室颤动阈值 降低猝死,ESC Expert Consensus Document on-blockers 2004,高血压早期已有SNS激活,Schlaish MP Hypertension 2004;43:169,去甲肾上腺素释放增加,肌肉交感兴奋,高血压时交感活性增加,BP 107/58,BP 148/102,ECG,MSNA,BP(mmHg),B,A,48 y
8、.o.femaleBP:107/58 mmHgMSNA:32 bursts per min 45 bursts per 100 hb,49 y.o.femaleBP:148/102 mmHgMSNA:42 bursts per min 77 bursts per 100 hb,150,100,50,p 0.01,MSNA(bursts/100 heartbeats),100,80,60,40,20,0,NT,EH,A,800,600,400,200,0,Total body NE spillover(ng/min),Cardiac NE spillover(ng/min),Ronal NE s
9、pillover(ng/min),B,80,60,C,40,20,0,250,200,150,100,50,0,NT,EH,NT,EH,NT,EH,Schlaich MP Circulation 2003;108:560,高血压交感活性增加和左心室肥厚的关系,去甲肾上腺素释放增加,左室重量/交感活性,A,70,60,50,40,30,20,10,0,HEART,Cardiac NE spillover(ng/min),NT,EH-,EH+,100,80,60,40,20,0,MSNA(burals/105 heartbeaths),MSNA,NT,EH-,EH+,250,200,150,100
10、,50,0,B,C,KIDNEY,NT,EH-,EH+,Renal NE spillover(ng/min),200,A,160,140,120,100,80,60,40,20,0,Left Vontilcular Miss inder(g/m2),200,C,160,140,120,100,80,60,40,20,0,Left Vontilcular Miss inder(g/m2),200,D,160,140,120,100,80,60,40,20,0,Left Vontilcular Miss inder(g/m2),180,180,180,0,10,20,30,40,50,60,70,
11、Cardiac NE Spillover(ng/min),0,200,400,600,800,1000,1200,1400,Whole Body NE Spillover(ng/min),180,160,140,120,100,80,60,40,20,0,Left Vontilcular Miss inder(g/m2),B,0,50,100,150,200,250,Reral NE Spillover(ng/min),0,20,40,60,80,MSNA(bursts/100 hoartboats),r=0.50;p 0.01,r=0.41;p=0.054,r=0.52;p 0.001,r=
12、0.50;p 0.01,100,Schlaish MP Hypertension 2004;43:169,高血压心脏NE和AII释放之间缺乏关系,动脉,冠脉窦,EH=原发性高血压,NT=正常血压,20,A,15,10,5,0,Anglotonsin II(fmol/ml),NT,EH,C,NT,EH,1.4,1.2,1.0,0.8,0.6,0.4,0.2,0.0,Anglotensln II/I ratlo(fmol/fmol,NT,EH,Anglotonsin I(fmol/ml),B,D,20,15,10,5,0,50,40,30,20,10,0,0,2,4,6,8,10,12,14,Ca
13、rdiac NESpillover(ng/min),CS Angiotensin II(fmol/ml),r=-0.009p=0.961,原发性高血压交感活性增加,中枢交感活性输出增加总体、心脏及肾脏去甲肾上腺素释放增加肌肉交感张力增加神经元去甲肾上腺素重新摄取降低左心室肥厚程度与心脏交感活性相关血管紧张素-II 浓度不增加,研究结果提示高血压时交感神经系统激活先于肾素血管紧张素系统激活,Slaich MP Hypertension 2004;43:169,因此治疗高血压时在阻断RAS之前阻断NE活性可能更为合理,治疗无并发症的高血压患者 阻滞剂可在ACEI或ARB之前应用,SNS 在心血管疾
14、病的重要性 高血压早期已有SNS激活-受体阻滞剂具有证据确鑿的 心脏保护作用-受体阻滞剂的临床实践,高血压病的一级预防,MAJOR CARDIOVASCULAR EVENTS Comparisons of different active treatments,RR(95%CI),Favours first listed,Favours second listed,BP difference(mm Hg),0.5,1.0,2.0,Relative Risk,ACEI vs.CA,CA vs.D/BB,ACEI vs.D/BB,0.97(0.92,1.03),1.04(0.99,1.08),1.
15、02(0.98,1.07),2/0,1/0,1/1,BPLT 2003,CARDIOVASCULAR DEATHComparisons of different active treatments,RR(95%CI),Favours first listed,Favours second listed,BP difference(mm Hg),0.5,1.0,2.0,Relative Risk,ACEI vs.CA,CA vs.D/BB,ACEI vs.D/BB,1.03(0.94,1.13),1.05(0.97,1.13),1.03(0.95,1.11),2/0,1/0,1/1,BPLT 2
16、003,TOTAL MORTALITYComparisons of different active treatments,RR(95%CI),Favours first listed,Favours second listed,0.5,1.0,2.0,Relative Risk,BP difference(mm Hg),ACEI vs.CA,CA vs.D/BB,ACEI vs.D/BB,1.04(0.98,1.10),0.99(0.95,1.04),1.00(0.95,1.05),2/0,1/0,1/1,BPLT 2003,Similar net effects on total card
17、io-vascular events of:ACE inhibitorsCalcium antagonistsDiuretics/beta-blockers,Conclusions I,高血压的一级预防 阿替洛尔随机研究(22150 病人年),HAPPHY,MRC 老年病人,两个研究荟萃分析,利尿剂组(n=1604),阿替洛尔组(n=1599),利尿剂组(n=1081),阿替洛尔组(n=1102),利尿剂组(n=2685),阿替洛尔组(n=2701),死亡例数,Wikstrand J et al,In Clinical trials in Hypertension,2001,pp 141-58
18、;The Steering Com.of the HAPPHY Trial,JAMA 1989;262:3273-74;MRC Working Party,Br Med J 1992;304:405-12.,26,33,134,160,160,200,0,50,100,150,200,250,美托洛尔预防高血压患者动脉粥样硬化研究（MAPHY）,3234例男性高血压患者，40-64y，平均随访 5.0年总病死率 22%（P=0.028）美托洛尔组4.0%（65/1609例）利尿剂组5.1%（83/1625例）与利尿剂组相比，美托洛尔组心血管猝死 30%（P=0.017）冠心病事件(致死+非致死
19、)24%（P=0.0010）,Wikstrand J et al JAMA 1988,一级预防-MAPHY,利尿剂,美托洛尔,p=0.028,随访时间，年,5,10,0,累计死亡数,90,50,0,累计死亡数,50,40,0,20,70,30,20,10,总死亡率,心血管猝死,利尿剂,美托洛尔,p=0.017,随访时间，年,5,10,0,Olsson G et alAm J Hypertens 1991,Wikstrand J et alJAMA 1988,一级预防 MAPHY致死性非致死性事件(至首次事件发生时间),冠脉事件,累计事件数,160,40,0,20,60,100,80,120,1
20、40,5,10,0,卒中事件,危险性降低 24%,利尿剂,美托洛尔,p=0.0010,利尿剂,美托洛尔,随访时间，年,Wikstrand et al,Hypertension 1991;17;579-88,MRC,IPPPSH 和 MAPHY研究结果荟萃分析10,951 例病人随机分组,随访51,100 病人年,总死亡率24720220%0.023猝死1016438%0.003冠心病(致死32526321%0.006+非致死性),随机分组非阻滞剂1 阻滞剂 危险性(n=5452)(n=5499)降低p值 事件发生数(%),研究终点,Wikstrand et al,In Clinical tri
21、als in Hypertension,ed Henry Black,New York,2001,pp 141-158,1主要为利尿剂,卡托普利与阿替洛尔：型糖尿病患者终点事件发生率比较（UKPDS）,UK Prospective Diabetes Study Group.BMJ 1998;317(7160):713-20,LIFE研究：主要结果,9193例高血压左室肥厚患者，平均随访54个月主要终点（中风/心肌梗死/心血管病死亡）氯沙坦组11%vs 阿替洛尔组13%（降低13.0%，p=0.021）二级终点（10项，包括总死亡率）致死或非致死中风降低24.9%（5%vs 7%p=0.001）
22、致死或非致死心肌梗死增高7.3%（p=0.49）心血管病死亡率降低11.4%（p=0.21）,Lancet 2002,所有终点总结,The area of the blue square is proportional to the amount of statistical information,阿替洛尔 苄氟噻嗪更好,0.50,0.70,1.00,1.45,主要终点Non-fatal MI(incl silent)+fatal CHD次要终点Non-fatal MI(exc.Silent)+fatal CHDTotal coronary end pointTotal CV event a
23、nd proceduresAll-cause mortalityCardiovascular mortalityFatal and non-fatal strokeFatal and non-fatal heart failure3级终点 Silent MIUnstable anginaChronic stable anginaPeripheral arterial diseaseLife-threatening arrhythmiasNew-onset diabetes mellitusNew-onset renal impairment事后分析 Primary end point+coro
24、nary revasc procsCV death+MI+stroke,2.00,Unadjusted Hazard ratio(95%CI)0.90(0.79-1.02)0.87(0.76-1.00)0.87(0.79-0.96)0.84(0.78-0.90)0.89(0.81-0.99)0.76(0.65-0.90)0.77(0.66-0.89)0.84(0.66-1.05)1.27(0.80-2.00)0.68(0.51-0.92)0.98(0.81-1.19)0.65(0.52-0.81)1.07(0.62-1.85)0.70(0.63-.078)0.85(0.75-0.97)0.86
25、(0.77-0.96)0.84(0.76-0.92),氨氯地平 培哚普利更好,only 14.3%of patients in the amlodipine group and 8.6%in the beta-blocker group remained on monotherapy at the end of the study,making this a trial of combination regimens.Dahlf said.Devereux said.I think the differences should be interpreted as being between r
26、egimens rather than between classes of drugs.,ASCOT,为药物联合方案之间的比较,而非 二类药物之间的比较 一级终点:非致死性MI和致死性冠心病 二组无差异-受体阻滞剂应用的是氨酰心胺,The results observed are not necessarily applicable to all blockers.They could simplyindicate particular disadvantages of the specific drugs usedeg.atenolol,as recently suggested.Bjrn
27、 Dahlf et al in ASCOT-BPLA,Lancet,Carlberg B Lancet 2004;364:1684,Atenol vs placebo in hypertension,Stroke,Mortality,AMI,CV Mortality,Atenolol in hypertension:is it a wise choice?Bo Carlberg,Ola Samuelsson,Lars Hjalmar Lindholm Lancet 2004,Hence,based on the results of our meta-analyses and on the e
28、ffects of atenolol in other cardiovascular disorders,we have doubts about the suitability ofatenolol as a first-line antihypertensive drug and as areference drug in outcome trials of hypertension.,However,pending further information,we believe the combination of a blocker and a diuretic should not b
29、e recommended in preference to the comparator regimenused in ASCOT-BPLA for routine use,but only forspecific circumstances.Bjrn Dahlf et al in ASCOT-BPLA,Lancet,Carlberg B,et al.Atenolol in hypertension:is it a wise choice?Lancet 2004;364:16841689.Lindholm LH,et al.Should-blockers remain first choic
30、e in the treatment of primary hypertension?A meta-analysis.Oct.18,2005.,Clinical Trials in Lindholms Meta-analysis,Dutch-TIA Coope(HEP)MRC-old STOP-H TEST IPPPSH(Oxprenolol)MRC-1,vs.placebo or no treatment,ASCOT-BPLA MRC-old Berglund NORDIL CONVINCE STOP-2 ELSA UKPDS HAPPHY Yurenev INVEST MRC-1 LIFE
31、,vs.other antihypertensive treatment,Berglund Yurenev MRC-1,Non-atenolol trials,如何认识-阻滞剂治疗高血压的荟萃分析(1),20个临床试验中,17个试验使用的-阻滞剂是阿替洛尔。其中3个为混合性。3个非阿替洛尔与其它降压药的比较试验:Berglund:：n=106 Yurenev：n=304 MRC：是唯一样本量较大的临床试验 n=8700 上述三试验应用的-阻滞剂均是普萘洛尔，属非选择性。而不同-阻滞剂存在药理异质性。MAPHY试验未包括在内,非阿替洛尔与其它降压药的比较试验,非阿替洛尔与其它降压药的比较试验,各
32、项终点事件(MI、总死亡率、卒中）均无显著差异 其中，MI、总死亡率、倾向有利于受体阻滞剂 L H Lindholm 等认为：所有的受体阻滞剂均不宜再作为 治疗高血压的首选药物 但从荟萃分析未能提供有力的证据,荟萃分析搜集的临床试验 治疗随访脱落率较高，影响 ITT分析 有的试验样本量太小,95%可信限极宽 异质性检验均有显著差异 缺乏整个试验期间的血压数据，因而，终点事件的差异未能用血压差值校正。药物的剂量、剂型与试验结果未作相关分析 入选试验跨度二十年，病人的特征与 高血压保健等均有改变,如何认识-阻滞剂治疗高血压的荟萃分析(2),Comment The end of blockers f
33、or uncomplicated hypertension?,Their current endorsement of blockers must surely be changed.But in the process they may be in danger of“throwing out the baby with the bath water”.Some patients genuinely do need blockers as their first line therapy，and there are also distinct theoretical hazards from
34、 their rapid discontinuation，particularly in patients who might be judged to be“coronary prone”.,D Gareth Beevers.Lancet 2005,Dr Peter S Sever(Imperial College London,UK)told a press conference here.We recognize that there are clearly subgroups of patients in whom beta blockers are indicated:”those
35、with a prior myocardial infarction or symptomatic coronary heart disease”.but in uncomplicated hypertension,I think the ASCOT data seriously raise questions about the future position of beta blockers in the management of hypertension.“We have reason to believe there may well be an adverse interactio
36、n between atenolol,thiazides,and statins and also a potential for beneficial interaction between amlodipine,perindopril,and statins,Effects of combined statin and beta-blocker treatment onone-year morbidity and mortality after acute myocardialinfarction associated with heart failure,30,25,20,15,10,5
37、,0,0,6,12,18,24,30,36,Month,Neither(n=830)Beta-blocker only(n=2004)Statin only(n=496)Both(n=1971),Endpoint rate(%),A Hognestad et al.Am J Cardid 2004;93:603-6,How to define the“uncomplicated hypertension”?,Importance of Primary Prevention,Women,0,Patients(%),Men,20,40,60,Murabito et al Circ 1993 88:
38、2548,Framingham Heart Study(n=5144)MI or SD as 1st Presentation,朝鲜战争死亡者 300人尸检平均年龄 22.1岁 77.3%冠脉AS 39%阻塞斑块 ENOS JAMA,Tuzcu Circ 1999,32 Year Old Female,Prevalence of Atherosclerosis by Donor Age,Atherosclerosis:Change in Approach,Early intervention pays long term dividends,John Deanfield,高血压病早期受体阻滞剂
39、的应用？高血压病早期已有交感神经系统的过度激活 受体阻滞剂在高血压病一级预防 对心脏的保护作用从未被超越 如何识别高血压病早期 晚期？高血压病早期仍应针对最佳人群 及早应用受体阻滞剂,冠心病高危患者心梗后患者心衰患者室上性和室性心律失常心源性猝死糖尿病,高血压病的二级预防,ACC/AHA指南：慢性稳定性心绞痛药物治疗（2002年版，推荐水平“Class I”）,阿斯匹林（无禁忌证者）-阻滞剂：作为首选抗心绞痛药（无禁忌证者）ACE抑制剂：用于合并糖尿病和（或）左室收缩功能异常的 确诊冠心病患者降胆固醇药：LDL-C 130mg/dl的冠心病患者（目标 100mg/dl）硝酸甘油舌下或喷雾：用于
40、迅速缓解心绞痛发作钙拮抗剂或长效硝酸盐：-阻滞剂有禁忌证的患者,全部患者必需 长期应用-阻滞剂,ESC Expert Consensus Document on-blockers 2004,慢性、稳定性冠心病,-阻滞剂治疗慢性稳定性冠心病指南（ESC 2004-阻滞剂专家共识）,UA/NSTEMI 指南如何使用-阻滞剂（ACC/AHA 2002）,若无禁忌证，-阻滞剂应早期开始使用(I类推荐)高危患者以及持续胸痛的患者，-阻滞剂先静脉注射再继以口服中、低危患者口服给予-阻滞剂休息时的目标心率为5060bpm，除非发生限制性副作用,NSTEMI ACS 应尽早开始应用-阻滞剂(I B)急性期后全
41、部病人均应接受-阻滞剂(I A)目标心率：50-60次/分,ESC Expert Consensus Document on-blockers 2004,-阻滞剂早期治疗急性心肌梗死的疗效28 项临床试验汇总分析（n27000）,ISIS Collaborative Group.Lancet 1986,2(8498):57-66,AMI后长期使用-阻滞剂的效益,总死亡率绝对危险显著降低（p0.0001）827/10452例（7.9%）：986/9860例（10.0%）总死亡率相对危险降低23%95%可信区间15%30%（p0.00001）非致死性心肌梗死绝对危险显著降低（p0.0001）549
42、/9643例（5.7%）：693/9198例（7.5%）非致死性心肌梗死相对危险降低26%95%可信区间17%34%（p0.0001）猝死相对危险降低30%95%可信区间20%40%（p0.00001）,Yusuf S,et al.Prog Cardiovasc Dis 1985,27(5):335-371,-阻滞剂降低老年心肌梗死患者死亡率,STEMI-阻滞剂治疗（ACC/AHA Guidelines 2004）,无禁忌证的患者应立即给予-阻滞剂口服治疗 不论是否同时接受溶栓治疗或直接 PCI 治疗（I类推荐、A级证据）除非有禁忌证或低危（心室功能正常或接近正常、再灌注成功、没有明显室性心律
43、失常），所有 STEMI 后的患者都应该接受-阻滞剂治疗。这种治疗是无限期的。（I 类推荐、A级证据）,-阻滞剂与心肌梗死 AMI:口服-阻滞剂适用于全部病人无禁忌症者(I A）i.v.-阻滞剂亦可应用（I B）MI后长期预防：口服-阻滞剂适用于全部病人无禁忌症者(I A）无限期使用。可：改善生存率、防止再梗、猝死 效益可见于并用再灌注治疗、ACE-I者 高危病人受益更大：大的、前壁梗死；糖尿病、心梗后缺血、迟发室律失常、Q波与非Q波心梗、老年人 下列情况效益大于危险：I 型糖尿病、COPD、严重外周血管病、PR间期达0.24秒,ESC Expert Consensus Document on
44、-blockers 2004,STEMI：-阻滞剂的相对禁忌证（ACC/AHA Guidelines 2004）,现有证据提示：-阻滞剂降低再梗死和死亡率的效益实际上超过其危险，包括非活动期轻度哮喘、胰岛素依赖糖尿病、COPD、严重外周血管疾病、PR0.24s、中度心力衰竭的患者。上述患者使用-阻滞剂时需加强监测，避免发生不良反应。大多数哮喘患者能够耐受心脏选择性的 1-阻滞剂。,二级预防：-阻滞剂的受益人群（ACC/AHA 2004 STEMI Guidelines）,接受或未接受再灌注治疗的患者病程早期或较迟开始接受-阻滞剂治疗的患者所有各种年龄组的患者高危患者得益最大（死亡率降低）：左室
45、功能异常、室性心律失常、未接受再灌注治疗的患者已经接受冠状动脉重建治疗（介入或搭桥手术）的患者，仍然需要长期-阻滞剂治疗；因为-阻滞剂能够进一步降低死亡率。,心肌梗死后的二级预防：-阻滞剂治疗（ESC 2004-阻滞剂专家共识）,-受体阻滞剂在冠心病中的应用从治疗指南到临床实践(全部I类推荐),稳定性心绞痛不稳定性心绞痛急性心肌梗死患者心肌梗死后患者相对禁忌证患者也应积极考虑使用 因为得益超过危险冠心病二级预防,心力衰竭,阻滞剂开拓了心力衰竭 生物学治疗的新纪元,美托洛尔提高扩张型心肌病的左心室射血分数,*P0.05*P0.0001#P=0.013，与标准治疗比较,Hall SA,et al.
46、J Am Coll Cardiol 1995;35:1154-1161,4035302520,左心室射血分数(),标准治疗美托洛尔,基线第一天第一月第三月,*,*,#,b受体阻滞剂之所以能从“心衰的禁忌症”转而成为常规治疗的一部分，就是因为走出了“短期”“药理学”治疗的误区，认识到了长期治疗的“生物学效应”，这也就是近年来心衰治疗概念发生根本性转变的依据，即：修复性策略-改变衰竭心脏的生物学性质。,n=10135，22个随机对照试验(不包括COPERNICUS和BEST)总死亡率的危险比：0.65(95%Cl 0.530.80)一致降低心衰病人的猝死率 MERIT-HF41%(P=0.002)
47、CIBIS II44%(P=0.001),b 阻滞剂治疗心力衰竭荟萃分析(Brophy JM et al.Ann Intern Med 2001),Placebo-controlled trials withbeta-blockers in heart failure,Packer et al.NE JM 1996;CIBIS II Invest.Lancet 1999;MERIT-HF Study Group.Lancet 1999BEST Investigators.Lancet 1999;Packer et al.NE JM 2001,CIBIS II,MERIT-HF,COPERNIC
48、US,BEST,CAPRICORN,Trial,n,Hazard Ratio(95%Cl),2.647,3.991,2.289,2.708,1.259,0.66(0.54-0.81),0.66(0.53-0.81),0.65(0.52-0.81),0.90(0.78-1.02),0.77(0.60-0.98),Mild-moderate-Severe CHF,Severe CHF,Post-MlCHF,0,0.2,0.4,0.6,0.8,1,Pre-planned Subgroup Analysis of Post-MI Patients,MERIT-HF,n=192648%of all ra
49、ndomized,Jnosi A,et al.Am Heart J 2003,MERIT-HF Subgroup Analysis of Post-MI Patients,Outcome in PMI Patients with Heart Failure,CAPRICORN(n=1959)and MERIT-HF(n=1926)1,1Subgroup analysis history of AMI 2Time to first event,CAPRICORN,All-cause mortality,All-cause mortality/CV hosp.2,MERIT-HF,23%,8%,R
50、isk reduction,p-value,p=0.03,Plac/Beta,151/116122/74,40%,p=0.0004,CAPRICORN,MERIT-HF,367/340326/258,ns,22%,p=0.002,The CAPRICORN Investigators.Lancet 2001;357:1385-1390.Janosi A et al.In preparation.,Relative risk and 95%CI,0.0,1.0,Metoprolol CR/XL 1,Metoprolol CR/XL 1,Carvedilol 1 2(1),Carvedilol 1
