沈潞華心衰講稿b受體阻滯劑

1、1,心力衰竭臨床治療進(jìn)展,首都醫(yī)科大學(xué)附屬北京友誼醫(yī)院　　　　 沈潞華,流行病學(xué),美國FRAMINGHAM心臟研究2000,發(fā)病率,年均心衰死亡率:30～50%,流行病學(xué),美國FRAMINGHAM心臟研究2000,5年存活率,中國心衰的發(fā)病率,35~74歲居民，15518人（10個(gè)省市20個(gè)城鄉(xiāng)抽樣調(diào)查）心率發(fā)病率0.9% 男性0.7% 女性1.0% 北

2、方1.4% 南方0.5% 城市1.1% 農(nóng)村0.8%隨著年齡的增高，患病率顯著上升,心力衰竭的形成過程,各種原因所致的心臟損害,,心臟結(jié)構(gòu)的改變,,心肌重量,,心室容量,,心室形態(tài),,心室重構(gòu),,心臟功能減退,心力衰竭,AMI 后神經(jīng)內(nèi)分泌激活界導(dǎo)左室重構(gòu)的結(jié)果,AMI,,血液動力學(xué)異常 (SV ? EF CO ?LVEDP ? 　心室擴(kuò)張, 　　　 　　　室壁張力增加）,,神經(jīng)

3、內(nèi)分泌激活(RAAS SNS細(xì)胞因子),心肌細(xì)胞肥厚心肌間質(zhì)纖維化 心肌細(xì)胞壞死 心肌毛細(xì)血管生長不足,,心功能受損,心肌缺血,心律失常,,左室重構(gòu)進(jìn)展,心力衰竭,,,,,,心衰時(shí)神經(jīng)內(nèi)分泌激活的危害性,循環(huán)和組織中NE, ANG II, 醛固酮, 內(nèi)皮素, 加壓素等,,鈉水潴留, 血管收縮,室壁張力升高, 心臟毒性作用, 刺激心肌纖維化,,,促進(jìn)心室重構(gòu), 加速心衰進(jìn)展,腎上腺素超負(fù)荷,血液動力學(xué)超負(fù)荷,心室重構(gòu)

4、心肌細(xì)胞肥大收縮功能異常細(xì)胞凋亡,交感神經(jīng)系統(tǒng)興奮,,,,,心力衰竭,,Cir 93;87(SVI):VI-40-48,Plasma noradrenaline and mortality in congestive heart failure,CHF過程,心衰惡化可能機(jī)制,心衰病情加重,心衰,,血腎素水平升高血管緊張素Ⅱ升高,交感神經(jīng)系統(tǒng)長期激活,心臟處于極度氧化應(yīng)激狀態(tài),,,對心臟產(chǎn)生毒性作用于心肌需氧增加,,,,,心

5、臟交感神經(jīng)活性?,血管緊張素 II,心肌肥厚， 凋亡， 缺血，心律失常，心肌重構(gòu)，纖維化,,,,心室重塑,?1受體 ?2受體 ?1受體,,,,,,,血管收縮,,衰竭心肌?-受體密度?，非胞內(nèi)重新分布 受體總數(shù)? 表面受體反應(yīng)性?（脫敏）主要下調(diào)為?1， ?2密度正常或相對提高主要部位為內(nèi)膜下選擇性? 衰竭時(shí)其受體密度為外膜的63? 5% （正常時(shí)應(yīng)為115 ? 6%） 非均一下調(diào)的機(jī)制

6、：血CA、局部NE釋放 心內(nèi)膜外膜血流量代謝不同,衰竭心肌?受體的改變,SNA增強(qiáng)是心衰的主要原因,衰竭時(shí)的心肌?1受體激酶mRNA水平減少,*P<0.05,正常,肥厚性心肌病,缺血性心臟病,,*,*,Ref: Circulation 1993,87:454-463.,β1 receptor mRNA, cpm,SNA增強(qiáng)是心衰的主要原因,?2 receptor mRNA, cpm,,正常,肥厚性心肌病,缺血性心臟病,R

7、ef: Circulation 1993,87:454-463.,衰竭時(shí)的心肌?2受體激酶mRNA水平不變,兒茶酚胺激活外周α1－受體引起外周血管收縮，而外周α2－受體使釋放入突觸間隙的兒茶酚胺再攝取。心力衰竭時(shí)，外周α－腎上腺素受體未下調(diào)，而其反應(yīng)可能被增加。心臟存在α－受體（幾乎全部為α1－受體），受刺激導(dǎo)致磷酯酰肌醇水解，生成三磷酸肌醇酯，釋放細(xì)胞內(nèi)貯存的鈣離子。正常狀態(tài)下，心臟總腎上腺素受體中α－受體所占的比例很小，但在衰

8、竭心臟，其比例升高。能介導(dǎo)心肌肥厚和增加心臟的興奮性。,心力衰竭時(shí)血管和心臟的?受體,1. 使衰竭心肌?受體密度?，恢復(fù)對CA敏感性2. 糾正交感支配不勻引起室壁局部異常運(yùn)動 恢復(fù)舒縮協(xié)調(diào)、改善心肌遲緩、充盈與順應(yīng)性3. 抑制交感神經(jīng)介導(dǎo)血管收縮、RAA釋放和繼發(fā)效應(yīng)4. 降低血CA，改善CA長期 ?所致代謝和心血管損害5. 降低心肌耗氧、乳酸釋放及心臟作功 糾正衰竭心肌中異常細(xì)胞內(nèi)Ca++的作用,?受體阻斷劑治

9、療充血心衰可能機(jī)制,抑制NE促使心臟肥大的作用，改善心肌供血。減輕因NE增加心肌細(xì)胞自律性、觸發(fā)心臟電活動，低血鉀所致心律失常。減輕因NE增加所致細(xì)胞凋亡。增加金屬蛋白酶組織型抑制劑（TIMP-I）的活性而不影響基質(zhì)金屬蛋白酶（MMP-3）活性，因而減少細(xì)胞外重塑，減少缺血心肌纖維化。 β阻滯劑通過降低心肌耗氧，降低CA水平，降低AngII水平及氧化損傷，擴(kuò)張血管作用而改善心功能，延緩心衰進(jìn)程。,?受體阻斷劑治療充血心衰可能機(jī)

10、制（續(xù)）,?-受體阻滯劑,降低心肌需氧,降低血漿兒茶酚胺水平,降低腎素血管緊張素Ⅱ,,抗氧化損傷擴(kuò)張血管,改善心功能,延緩心衰進(jìn)程,,,,,,,,,,?受體阻斷劑治療充血性心衰,Interactions between betablockers and promoters of congestive heart failure and arrhythmias in CHF,How can betablockers improv

11、e myocardial energy balance in heart failure?,↓Heart rate↑Diastolic flow time↑ Relaxation↓ Myocardial restriction↑ Perfusion pressure↓ Filing pressure↓ Hypertrophy↓ Free fatty acids↓ Remodeling,目的：評估Bisoprolol對心衰

12、死亡率影響設(shè)計(jì)：隨機(jī)、雙盲、安慰劑對照、多中心病人：641例各種病因心衰，18~75歲，Ⅲ/Ⅳ級（EF<0.4） （除外：限制、肥厚心、瓣膜病、3月內(nèi)AMI）、 Biso,1.25mg/d?5mg/d隨訪：1.9?0.1年 對照：常規(guī)（強(qiáng)心、利尿、CCB）結(jié)果：

13、 治療組 安慰劑組 死亡率 53/320(16.6%) 67/321(20.9%) p =0.22,,,,CIBIS(cardiac Insufficiency Bisoprolol Study)(Lencet 1994;90:1765),CIBIS Ⅱ-心功能不全比索洛爾研究,雙盲，安慰劑對照的隨

14、機(jī)實(shí)驗(yàn)2647例患者，包括（NYHA Ⅲ+Ⅳ）常規(guī)治療（利尿劑+AECI）的基礎(chǔ)上加比索洛爾,,CIBISⅡ-生存率,1.00.80.6,0,0,200,400,600,800,比索洛爾死亡156例(n=1327),安慰劑死亡228例(n=1320),P<0.0001,入選后時(shí)間(天),比索洛爾組全因死亡率降低34%,,,MERIT-HF 結(jié)果,總死亡累積百分率的Kaplan-Meuer曲線經(jīng)2次中期階段分析校正的P值

15、,,下降34%,MERIT-HF結(jié)果,下降38%,心血管死亡致死的累積百分率的Kaplan-Meier曲線,,,猝死致死的累積百分率的Kaplan-Meier曲線,MERIT-HF 結(jié)果,下降41%,心力衰竭惡化致死的累積百分率的Kaplan-Meier曲線,MERIT-HF 結(jié)果,下降49%,,Carvedilol,同時(shí)阻滯β1，β2，α1受體阻滯β受體 　 心率，心縮力↓阻滯α1受體 　 前，后負(fù)荷↓,抗自由基，抗氧化損傷直

16、接清除氧自由基抑制氧自由基介導(dǎo)的脂質(zhì)過氧化保護(hù)內(nèi)源性抗氧化系統(tǒng)α,對心率影響小　　阻滯β受體→心率↓　　阻滯α1受體→心率↑,心率變化小,→ 抑制心肌細(xì)胞凋亡,心肌需氧,↓改善心功能,,,Injury to heart,Sympathetic activation,Disease progression,,,,,,,,Metoprolol,Bucindolol,Carvedilol,Sympathetic Nervous Sy

17、stem Activation in Heart Failure,Bisoprolol,?2receptors,?1 receptors,?1receptors,Nebivolol,?1 receptors,卡維地洛降低輕中度慢性心衰病人的死亡危險(xiǎn)（NYHA-II~III）,,,,,,,,,,,,,,,Carvedilol（n=696）,Placebo（n=398）,Survival 1.0,0.9,0.8,0

18、.7,0.6,0.5,0 50 100 150 200 250 300 350 400,Days,死亡危險(xiǎn) 65%,,P<0.001,US Carvedilol Program,COPERNICUS研究,隨機(jī)分組2289 例嚴(yán)重心力衰竭患者按 1:1 隨機(jī)分組至安慰劑組卡維地洛組起始劑量為 3.125 mg 每日2次，每二周劑量加倍，

19、直至達(dá)到目標(biāo)劑量 25 mg 每日2次?；颊叻盟苣褪艿淖罡邉┝?,卡維地洛降低重度心衰病人死亡危險(xiǎn) （ NYHA-III~IV）,,Placebo,% Survival,90,80,70,60,50,0 4 8 12 16 20 24 28,Months,Carvedilo

20、l,COPERNICUS Study,35% P=0.00014,,100,卡維地洛降低極重心衰病人死亡率,,,100,,,,,,80,60,40,20,3,9,0,6,21（月）,18,15,12,,Carvedilol,Placebo,39% (P = 0.009),%生存,觀察時(shí)間,,,哥白尼研究高危亞組,,,P=0.0017,300,900,700,500,,,安慰劑,卡維地洛,,20%,任何原因,,,P=0.0002,0,

21、600,400,200,,,,28%,心血管原因,,,P=0.0001,0,450,300,150,,,,33%,心力衰竭,安慰劑,卡維地洛,安慰劑,卡維地洛,COPERNICUS研究住院率,0,Packer et al (2000),CIBIS-II Investigators (1999),,,,,,,,,,,,,,,0 200 400 600 800

22、,1.00.80.60,Bisoprolol,Placebo,Time after inclusion (days),p<0.0001,Survival,Risk reduction = 34%,The MERIT-HF Study Group (1999),Months of follow-up,Mortality %,0,3,6,9,12,15,18,21,20,15,10,5,0,Placebo

23、,Metoprolol CR/XL,p=0.0062,Risk reduction = 34%,,,,,,,,,,,,,,,,? Blockade in systolic HF –All-cause mortality,CIBIS-II,MERIT-HF,Months,8,4,12,16,20,24,28,70,80,90,100,60,50,Placebo,Carvedilol,Nominal p=0.0001435% risk

24、reduction,% Survival,COPERNICUS,,,,,,,,,,,,,,,,,,,,,0.2,0.4,0.6,0.8,1.0,1.2,Carvedilol (US trials)All cause mortalitySudden deathBisoprolol (CIBIS-II)All cause mortalitySudden deathMetoprolol (MERIT-HF)All cause m

25、ortalitySudden death,Risk ratio (95% CI),?阻斷劑降低心衰死亡率和猝死率,重度心力衰竭,,Myocardial 　function,Time,,The two modes of death in heart failure,,,,Sudden death,Progressive heart failure death,,,Antiremodeling effects of metoprolol

26、CR/XL in congestive heart failure,,,,,,,,,,,,,,,,,,,,,,,,,,,,,-30,-25,-20,-15,-10,-5,0,5,10,Δ LVEDVI ml/m2,Δ LVESVI ml/m2,Δ Ejection fraction units,,,Placebo,,Metoprolol,ml/m2 or EF units,Ad

27、apted from Groenning BA et al J Am Coll Cardiol 2000;36:2072,p=0.01,P=0.001,p=0.03,Beta-Blockers Are Underutilized in Heart Failure,,Annual Prescriptions for Heart Failure (1000s),MDC (1993)CIBIS I (1994),U.S Carvedilol

28、ANZ,MERIT-HFCIBIS II,COPERNICUS,,,,,,,,,,,,,,,,,,,,,,0,4,000,8,000,12,000,16,000,20,000,Total prescriptions for heart failure,,,Diuretics,,,ACEs,,,Digoxin,,,,,,Beta-blockers,,,,,,,,,,,,,,,,,,IMS NPA, NDTI,,2000年上海16家二三

29、級醫(yī)院心力衰竭藥物使用率調(diào)查,中華心血管病雜志。 2001，29（11）：644-648,國內(nèi)心力衰竭藥物使用率調(diào)查顯示： β受體阻滯劑僅為27.20%,,Komajda M et al. Eur Heart J 2003,Utilisation of ?-Blockade for CHFin Clinical Practice,33,21,21,17,62,37,36,87,0%,50%,100%,Diuretics,ACE Inh

30、ibitors,β-blockers,Digoxin,Nitrates,Calcium antagonists,Spironolactone,ACEi, βB, diuretics,Why Do Physicians Not Give Beta-blockers to Patients?,Patient is too old for beta-blockersPatient has COPDPatient has Diabetes

31、 mellitusPatient has BP which is too lowPatient has EF which is too lowBeta-blockers cause impotence, claudication and depressionCan only tolerate low doseToo expensive drugs -no cost-benefit,Myths about side effect

32、s and tolerability:,MERIT-HF: Risk reduction with Beta-blockade in the Elderly,Deedwania P et al. Circulation 104 (Suppl II):II-753,,,<65 yearsn=2009,>65 yearsn=1982,,,,,,,,,,¯30%,¯37%,¯38%,¯

33、43%,¯8%,¯61%,¯22%,¯38%,All Cause Mortality,Sudden Death,Death/Worsening HF,Hosp for worsening HF,Risk reduction (%),-60,-50,-40,-30,-20,-10,0,10,20,-70,Why Do Physicians Not Give Beta-blockers to

34、Patients?,Patient is too old for beta-blockersPatient has COPDPatient has Diabetes mellitusPatient has BP which is too lowPatient has EF which is too lowBeta-blockers cause impotence, claudication and depressionCan

35、 only tolerate low doseToo expensive drugs -no cost-benefit,Myths about side effects and tolerability:,Meto CR/XL PlaceboNet differenceAdverse event1 (Meto CR/XL-Placebo) n=1990n=2001 One year of trea

36、tment,Infection25874-0.8%Dyspnoea30270.1%Pulmonary oedema89-0.1%Bronchospasm68-0.1%COPD367-0.1%Haemoptysis17-0.3%Any respiratory AE　　　　108　　　　121-0.7%,The MERIT-HF Study Group,R

37、espiratory System Disorders: All AE/SAE Reported,,1One patient may have more than one AE in a system organ class2Pneumonia, Bronchitis or Respiratory infection3Chronic obstructive pulmonary disease,,,,Why Do Physicians

38、 Not Give Beta-blockers to Patients?,Patient is too old for beta-blockersPatient has COPDPatient has Diabetes mellitusPatient has BP which is too lowPatient has EF which is too lowBeta-blockers cause impotence, cla

39、udication and depressionCan only tolerate low doseToo expensive drugs -no cost-benefit,Myths about side effects and tolerability:,MERIT-HF: Risk Reductions in Diabetics Patients,Deedwania P et al. ACC 2002,,,-30,-20,-1

40、0,0,10,,,,,All Deaths,All deaths/All Hosp,All Deaths/ HF Hosp,¯ 21%,¯ 15%,¯ 29%,Risk reduction* vs placebo (%),n=984,* Time to first event,5,-5,-15,-25,Meto CR/XL PlaceboNet differenceAdverse event

41、(Meto CR/XL-Placebo) n=1990n=2001 One year of treatment,Hyperglycaemic reaction24200.2%Hypoglycaemic reaction430.1%Diabetic ulcer44 - New onset diabetes mellitus3

42、4-0.1%Total number of patients35310.2%,The MERIT-HF Study Group, JAMA 2000;283:1295-1302,Diabetes Mellitus: All AE/SAE Reported,The MERIT-HF Study Group,,,,,Why Do Physicians Not Give Beta-blockers to Patients?,

43、Patient is too old for beta-blockersPatient has COPDPatient has Diabetes mellitusPatient has BP which is too lowPatient has EF which is too lowBeta-blockers cause impotence, claudication and depressionCan only tole

44、rate low doseToo expensive drugs -no cost-benefit,Myths about side effects and tolerability:,SBP: 120 (mean 142 mm Hg),144/213167/226,Total mortality/hospitalization for heart failureEffect of systoilic blood pressure

45、,Favours metoprolol,Favours placebo,Why Do Physicians Not Give Beta-blockers to Patients?,Patient is too old for beta-blockersPatient has COPDPatient has Diabetes mellitusPatient has BP which is too lowPatient has E

46、F which is too lowBeta-blockers cause impotence, claudication and depressionCan only tolerate low doseToo expensive drugs -no cost-benefit,Myths about side effects and tolerability:,EF: 0.25 (mean 0.32),146/231165/20

47、8,Favours metoprolol,Favours placebo,Total mortality/hospitalization for heart failureEffect of ejection fraction,EF: 0.25 (mean 0.32),Total mortality/hospitalization for heart failureEffect of ejection fraction,Why Do

48、 Physicians Not Give Beta-blockers to Patients?,Patient is too old for beta-blockersPatient has COPDPatient has Diabetes mellitusPatient has BP which is too lowPatient has EF which is too lowBeta-blockers cause imp

49、otence, claudication and depressionCan only tolerate low doseToo expensive drugs -no cost-benefit,Myths about side effects and tolerability:,Depression59-0.2%Impotence630.1%Anxiety25-0.2%Other psychi

50、atric AE1623-0.4%Any psychiatric AE2837-0.5%,,The MERIT-HF Study Group, JAMA 2000;283:1295-1302,Psychiatric Disorders: All AE/SAE Reported,*One patient may have more than one AE in a system organ class,The MER

51、IT-HF Study Group,Meto CR/XL PlaceboNet differenceAdverse event* (Meto CR/XL-Placebo) n=1990n=2001 One year of treatment,,,,Why Do Physicians Not Give Beta-blockers to Patients?,Patient is too old for

52、 beta-blockersPatient has COPDPatient has Diabetes mellitusPatient has BP which is too lowPatient has EF which is too lowBeta-blockers cause impotence, claudication and depressionCan only tolerate low doseToo expe

53、nsive drugs -no cost-benefit,Myths about side effects and tolerability:,Why Do Physicians Not Give Beta-blockers to Patients?,Patient is too old for beta-blockersPatient has COPDPatient has Diabetes mellitusPatient h

54、as BP which is too lowPatient has EF which is too lowBeta-blockers cause impotence, claudication and depressionCan only tolerate low doseToo expensive drugs -no cost-benefit,Myths about side effects and tolerability:

55、,Hospitalizations in MERIT-HF trial,,,,,,,,,,,,,,,,,,,,,,,,,,514,349,362,379,424,441,0,200,400,600,800,1000,1200,1400,Standard Rx,Metoprolol,Hospitalizations per 1000 Patients,Non-CVD Hosp,Other CVD Hosp,HF Hosp,Total Nu

56、mber of Days in Hospital,Heart failure,p<0.00001,-36%,All-cause,p=0.0042,-17%,The MERIT-HF Study Group, JAMA 2000;283:1295-1302,ACE inhibitor,,Fluid retention,Diuretics,No fluid retention,Beta-blocker,,Digoxin,,,,Spir

57、onolactone,,,Nitrates + hydralazine,,,,,Algorithm for treatment ofsystolic heart failure,所有慢性收縮性心力衰竭，NYHA心功能II、III級患者，LVEF<40%，病情穩(wěn)定者均必須應(yīng)用β受體阻滯劑，除非有緊急或不能耐受。應(yīng)告知患者：（1）癥狀改善常在治療2-3個(gè)月后才出現(xiàn)，即使癥狀不改善，也可防止疾病的進(jìn)展。（2）不良反應(yīng)常發(fā)生在治療的早

58、期，一般不妨礙長期用藥。β受體阻滯劑不能應(yīng)用于“搶救”急性心衰患者，包括難治性心衰需靜脈給藥者。NYHA心功能IV級心衰患者，需待病情穩(wěn)定（4天內(nèi)未靜脈給藥；已無液體潴留并體重穩(wěn)定）后，在嚴(yán)密監(jiān)護(hù)下由?？漆t(yī)生指導(dǎo)應(yīng)用。應(yīng)在ACEI和利尿劑基礎(chǔ)上加用β受體阻滯劑、地高辛也可應(yīng)用。,中華醫(yī)學(xué)會心衰治療指南,β受體阻滯劑的應(yīng)用要點(diǎn)：,β受體阻滯劑的禁忌癥:支氣管痙攣性疾病心動過緩（心率小于60次/分）二度以上房室傳導(dǎo)阻滯（除非已安

59、裝起博器）有明顯液體潴留，需大量利尿劑者，暫時(shí)不能應(yīng)用。β受體阻滯劑的起始和維持起始治療前患者已無明顯液體潴留，體重恒定，利尿劑已維持在最合適劑量。β受體阻滯劑必須從極小量開始，每2-4周劑量加倍。達(dá)到最大耐受量或目標(biāo)劑量后長期維持，不按照患者的治療反應(yīng)來確定劑量。,β受體阻滯劑的應(yīng)用要點(diǎn)：,中華醫(yī)學(xué)會心衰治療指南,β受體阻滯劑應(yīng)用時(shí)的監(jiān)測低血壓：特別是有α-受體阻滯作用的制劑易于發(fā)生，一般在首劑或加量的24-48小時(shí)內(nèi)發(fā)生。

60、可將ACEI或血管擴(kuò)張劑與β受體阻滯劑在每日不同時(shí)間應(yīng)用，一般不將利尿劑減量。液體潴留和心衰惡化：常在起始治療3-5天出現(xiàn)體重增加，如不處理，1-2周后常致心衰惡化。應(yīng)告知患者每日秤體重，如有增加，立即加大利尿劑用量。心動過緩和房室阻滯：與β受體阻滯劑劑量大小成正比，如心率小于55次/分，或出現(xiàn)二、三度房室傳導(dǎo)阻滯，應(yīng)將β受體阻滯劑減量或停用。,β受體阻滯劑的應(yīng)用要點(diǎn)：,中華醫(yī)學(xué)會心衰治療指南,,,對心力衰竭患者合理加用β受體阻滯劑

61、治療------穩(wěn)定、逆轉(zhuǎn)左室功能不全改善生存率減輕癥狀提高生活質(zhì)量　　　成為心功能不全患者規(guī)范治療的一個(gè)重要組成部分,最大耐受量以清醒靜息時(shí)心率≥55次/分,如何使用ß受體阻斷劑（1）,,55,中華心血管病雜志。 2002，30（1),,如何使用ß受體阻斷劑（2）,靶劑量后應(yīng)避免突然撤藥，以防引起病情惡化如患者不能耐受，亦可用較低劑量即最大耐受量,中華心血管病雜志。 2002，30（1),,,,在用藥

62、期間如心衰有加重,首先調(diào)整利尿劑和ACEI劑量，以達(dá)到臨床穩(wěn)定,中華心血管病雜志。 2002，30（1),如何使用ß受體阻斷劑（3）,如病情惡化需靜脈用藥，可減量或停用,中華心血管病雜志。 2002，30（1),如何使用ß受體阻斷劑（4）,,,CAPRICORN研究目的 / 設(shè)計(jì),在現(xiàn)代治療的基礎(chǔ)上，評價(jià)卡維地洛對急性心肌梗死后左心室功能障礙的患者的臨床轉(zhuǎn)歸的影響在左心室射血分?jǐn)?shù)? 40%合并或不合并心力衰竭患者中

63、，進(jìn)行多中心, 隨機(jī), 平行，安慰劑對照試驗(yàn),CAPRICORN研究,各研究者的最佳治療,一般 3 – 5 天但是MI后可長達(dá) 21天,卡維地洛 (n=975),安慰劑 (n=984),遞增,遞減,,,,,,,起始劑量為 6.25 mg 或 3.125 mg 每日2次在2-4周內(nèi)遞增至最大耐受劑量目標(biāo)劑量為 25 mg 每日2次,(n=1959),維持,直到發(fā)生 633 次事件的時(shí)間 平均隨訪: 1.3 年,,,,1,無事件

64、比例,年,0.9,0.85,0.7,0.75,0.8,0.95,0,0.5,1,1.5,2,2.5,卡維地洛,安慰劑,與安慰劑相比，降低23% P = 0.031,CAPRICORN研究主要終點(diǎn): 所有原因的死亡,CAPRICORN: 降低復(fù)發(fā)性心梗,無事件百分率,卡維地洛,安慰劑,年,0,0.92,0.2,0.4,0.6,0.8,1.0,1.2,1.4,1.6,1.8,0.94,0.96,0.98,1,,,,,,,CAPRICOR

65、N: 抗心律失常作用,房顫/房撲,相對危險(xiǎn)降低%,所有SVA,所有VA,VF/VT,59%P=0.0003,63%P<0.0001,76%P<0.0001,,,,,,,,,,52%P=0.0015,,0,-10,-20,-30,-40,-50,-60,-70,-80,,,,CAPRICORN: 明顯降低心梗后心律失常,無事件比值,年,無事件比值,年,卡維地洛,安慰劑,卡維地洛,安慰劑,P=0.0003,P<0.

66、0001,房撲或房顫,室性心動過速或心室顫動,,,,,,,0,0.5,1.0,1.5,2.0,2.5,0.90,0.92,0.94,0.96,0.98,1.00,,,,,,,,,0,0.5,1.0,1.5,2.0,2.5,0.90,0.92,0.94,0.96,0.98,1.00,,,CAPRICORN研究,是目前唯一的評價(jià)? 阻滯劑治療急性心肌梗死后出現(xiàn)左心室功能障礙的大規(guī)模臨床試驗(yàn)在已獲目前心肌梗死最佳治療(溶栓、血運(yùn)重建、AC

67、E抑制劑)的基礎(chǔ)上，卡維地洛仍顯示出其顯著的臨床益處如果不存在特異的反指證，應(yīng)考慮給予所有急性心肌梗死后左心室功能障礙的患者卡維地洛治療對心肌梗死后的患者，卡維地洛應(yīng)及早使用并長期維持,,0 wk,,,,,,,,,,,,隨訪 (月),,,CARMEN 研究設(shè)計(jì),組 2,,,,,,,,,,安慰劑 (雙盲),,,,,,,卡維地洛 (雙盲),組 3,安慰劑 (雙盲),首要終點(diǎn): 不同治療組間 LVESVI 的比較,第 6 月,第 12 月

68、,第 18 月,,NS,,P<0.002,基線,LVESVI = left ventricular endsystolic volume index,LVESVI (biplane) [ml/m2],,,4,2,0,-2,-4,-6,-8,-10,++,++,++,+,+,+,M6,M12,M18,M6,M12,M18,M6,M12,M18,+P<0.05, ++P<0.001,CARMEN: 卡維地洛®改善