心力衰竭药物治疗新证据与新视野课件

1、心力衰竭药物治疗新证据与新视野李勇复旦大学附属华山医院心脏科上海 200040治疗心力衰竭的药物1、强心苷类药物2、利尿剂3、ACE抑制剂及血管紧张素II（AT1）受体拮抗剂4、受体阻断剂 5、其他治疗CHF的药物： （1）钙拮抗剂 （2）磷酸二酯酶抑制剂 （3）其他血管扩张剂：长效硝酸酯类，肼苯哒嗪 DIG 研究50403020100Placebon=3403Digoxinn=3397480122436Mortality %N Engl J Med 1997;336:525Monthsp = 0.8DigitalisN=6800NYHA II-III 0.6Probability of De

2、ath0Placebo (273)Prazosin (183)Hz + ISDN (186)Months0.70.50.30.40.20.1N Engl J Med 1986;314:1547Nitrates06121824303642V-HeFT-I研究combination of hydralazine (300mg/day) and isosorbide dinitrate (160mg/day23% reduction in mortalityPlaceboEnalapril12111098765Probabiility of DeathMonths0.10.800.20.30.70.

3、40.50.6p 0.001p 0.002N Engl J Med 1987;316:142943210CONSENSUS 研究253 patients with class IV heart failureEnalapril： 2.5-40mg/day31% reduction in mortality50403020100Months0612p = 0.0036% Mortality241830364248Enalapriln=1285Placebon=1284N Engl J M 1991;325:293n = 2589CHF - NYHA II-III- EF 35SOLVD (Tre

4、atment) 研究11.3% reduction in mortality0,540,480122448600.750.500.2500.470.360.250.130.090.310.180.4236Monthsp = 0.08N Engl J Med 1991; 325:303EnalaprilHZ + ISDNn = 804p = 0.016Probability of deathNitrate + HydralazineVsEnalaprilV-HeFT II研究心力衰竭药物治疗AsymptomaticMild to moderateModerateLV dysfunctionCHF

5、to severe CHFACE inhibitorDigoxinDigoxinBeta blockerDiureticsDiureticsACE inhibitorACE inhibitorBeta blockerBeta blockerSpironolactone 心力衰竭治疗指南：常规治疗所有收缩性心力衰竭患者必需应用ACE抑制剂，包括无症状性心力衰竭，LVEF ACE抑制剂？ARBsACE抑制剂 ACE抑制剂？0.20.40.60.8No. of PatientsFavors Valsartan Favors Placebo Combined end pointACE-I y, BB

6、n 3034ACE-I y, BB y 1610ACE-I n, BB n 226ACE-I n, BB y 140MortalityACE-I y, BB n 3034ACE-I y, BB y 1610ACE-I n, BB n 226ACE-I n, BB y 1401.21.41.61.81.0Val-HeFT: Combined Morbidity/Mortality in SubgroupsBB = -blocker; y = yes; n = no.Cohn J et al. N Engl J Med. 2001;345:1667-1675.CHARM-Added: 预设亚组,

7、心血管死亡或心力衰竭住院-阻滞剂 Yes 223/702 274/711 No260/574264/561ACE I.Yes232/643275/648推荐剂量No251/633263/624所有患者 483/1276538/1272Candesartan安慰剂Candesartan betterHazard ratioPlacebo better0.60.81.01.21.4P value fortreatment interaction0.140.26McMurray JV et al. Lancet. 2003. /extras/03art7417web.pdfESC Guideline

8、s on the diagnosis and treatment of CHF, EHJ 2005对ACE抑制剂有不能耐受症状的患者， ARBs 可以很好的替代ACE抑制剂，可以降低发病率和死亡率 (证据水平 B, I级)ARBs 和 ACE抑制剂在治疗CHF方面，有相似的功能 (证据水平 B, I级)急性心肌梗死后有心衰 或左室功能障碍征兆 ，ARBs 与 ACE 抑制剂有相似的疗效 (证据水平 B, I级)联合使用ARBs与ACE抑制剂治疗有症状的患者，能够降低死亡率 (证据水平 B, IIa级) 和心衰的入院治疗率 (证据水平 A, I级) The Role of ARBs in Hea

9、rt Failure坎地沙坦 4-32缬沙坦 80-320依普沙坦 400-800氯沙坦 50-100依贝沙坦 150-300替米沙坦 40-80通常被用来治疗心衰的ARBs 可降低死亡率/发病率的ARB 每日剂量（mg)ESC Guidelines on the diagnosis and treatment of CHF, EHJ 2005Stable dosesof diuretics,digoxin, nitratesBaseline/screeningUp-titrationPhase A0 wkUp-titration Phase BMaintenancePhase91836121

10、50Down-titrationPhaseFollow-up (months)CARMEN 研究设计Group 2Placebo (blinded)Carvedilol (blinded)Group 1Carvedilol (blinded)Ealapril (blinded)Enalapril (blinded)Group 3Enalapril (blinded)Placebo (blinded)CARMEN Primary Endpoint: Comparison of LVESVI Between TreatmentsMonth 6Month 12Month 18NSP0.002Base

11、lineLVESVI (biplane) ml/m2LVESVI = left ventricular endsystolic volume indexBisoprolol-first (o.d.)Enalapril-first (b.i.d.)Bisoprolol o.d.Enalapril b.i.d.Bisoprolol o.d.Enalapril b.i.d weekStudy end1 - 2.5 years0 2 4 6 8 10 26 28 30 32 34 36 weekStudy end1 - 2.5 yearsFirst up-titrationFirst up-titra

12、tionSecond up-titrationSecond up-titrationMaintenance periodMaintenance periodSecond maintenance period22-100 weeksSecond maintenance period16-94 weeks1.252.53.755.07.51.252.53.755.07.52.55.02.55.0* * * * * * * * * * * * * * * * . * * * * * * = visits10.0 mg10.0 mg10.0 mg10.0 mgCIBIS III 研究设计Bisopro

13、lol o.d.Enalapril b.i.d0 2 4 6 8 10 26 28 30 32 34 36* * * * * * * * * * * * * * * * . * * * * *DOI: 10.1161/CIRCULATIONAHA.105.582320 不同-受体阻断剂的药理学差异121 blockadeantioxidant blockade blockade (vasodilat.)effects美托洛尔+-比索洛尔+-阿替洛尔+-卡维地络+布辛洛尔+(+)-奈比洛尔+-(+)-受体阻断剂治疗心力衰竭1-受体阻断是-受体阻断剂治疗获益的主要来源在获得等同的1-受体阻断作用下

14、，其他作用1阻断胰岛素敏感性血脂代谢 可否带来进一步的获益？0.500.751.001.251.50SexMaleFemaleAge25%Heart rate80 beats/min80 beats/minSystolic BP 3 monthsLV function 35% ( 40% if LV dilated per echo)90% receiving diuretics, 69% ACE-inhibitor, 17% angiotensin receptor blocker, 74% beta-blockerA-Heft Trial: Primary Endpoint Presented at AHA 2004All individual components of the primary composite