1、diureticdigoxindiureticdigoxinACEIdiureticdigoxinACEIdiureticdigoxinACEIBeta blockerdiureticdigoxinACEIBeta blockerdiureticdigoxinACEIBeta blockerARBSOLVD-T(1991)RRR 21%CIBIS-2(1999)RRR 33%CHARM-Added(2003)(Beta-blocker subgroup)RRR 30%Improving Survival in CHF One-year MortalityCV Death,MI,or HFby
2、TreatmentPfeffer,McMurray,Velazquez,et al.N Engl J Med 2003;349CaptoprilMonthsValsartan vs.Captopril:HR=0.96;P=0.198Valsartan+Captopril vs.Captopril:HR=0.97;P=0.36900.10.20.30.4061218243036Probability of EventValsartanValsartan+CaptoprilACE-I in HF-Who and How?HFSA Practice Guidelines 2004All pts(sy
3、mptomatic and asymptomatic)with LV systolic dysfunction(LVEF 2.0 mg/dl or serum potassium is 5.0 mmol/L.ACEI should be titrated as tolerated,in conjunction with BBs,to target doses used in clinical trials.Weight Of Evidence:-BlockadeOver 18,000 patients evaluated in long-term placebo-controlled clin
4、ical trialsImprovement in cardiac function and symptoms;(equivocal effects on exercise tolerance)Decrease in all-cause mortality by 30%-35%(P.0001);effect shown in 5 individual trialsDecrease in combined risk of death and hospitalization by 35%-40%(P9 monthsNYHA Class I-IVCOMPANIONHypothesesBiventri
5、cular CRT alone decreases combined all-cause mortality and all-cause hospitalization.ICD prevents sudden death1520 Patients Randomized Medical vs CRT vs CRT-ICD Endpoint:All-cause MortalityICD ImplantsMayo ICDs/yearCP985319-12Year(1985-2003)“Even the wealthiest nationscannot afford to pay to use eve
6、ry medical advance in any patient who might benefit.”.Thomas Bigger,Lancet,2001PHYSIOLOGIC FACTORS AFFECTING VENTRICULAR RELAXATIONCHARM Programn=3025LVEF 40%ACEI treated/not treatedCHARM-“Added”CHARM-“Preserved”3 component trials comparingcandesartan to placeboCHARM-“Alternative”n=2028 LVEF 40%ACEI
7、 intolerantn=2548LVEF 40%ACEI treatedPrimary outcome:CV death or CHF hospCHARM-Preserved Investigator-reported CHF HospitalizationsP=0.014P=0.017Patients hospitalizedHospitalizationsPlaceboCandesartanProportion of patients(%)Number of episodesHR=0.85RRR=29%New Approaches to the Patient with Heart Fa
8、ilureAssessment of LV functionLow LVEFEjection fraction 40%Signs/symptoms offluid retentionNo signs/symptoms offluid retentionDiureticACEI/or ARBBeta blockerPreserved LVEFEjection fraction 40%ARBARBNo signs/symptoms offluid retentionDigoxinSpironolactoneNYHA Class II/IIINYHA Class III/IVCOPERNICUS:O
9、UTCOMESCHARM“Added”CHARM“Preserved”CHARM Program3 component trials comparing candesartan to placebo in patients with symptomatic heart failureCHARM“Alternative”n=2028 LVEF 40%ACEI intolerantn=2548LVEF 40%ACEI treatedn=3025LVEF 40%ACEI treated/not treatedPrimary outcome for Overall Program:All-cause
10、deathPrimary outcome for each trial:CV death or CHF hospitalizationMortality Benefit of Beta Blockers and ACEIs in CHF trials11.915.67.812.40246810121416%death at 1 yearSOLVD (1991)diureticdigoxin diuretic digoxin ACEIdiuretic digoxin ACEIdiuretic digoxin ACEI Beta blockerCIBIS IIMERIT-HF(1999)McMur
11、ray 2001CHARM-Overall:Permanent Study Drug DiscontinuationsPlaceboCandesartan0510152025Percent of patientsP0.0001P0.0001P0.0001P0.0001Hypo-tensionIncreased creatinineIncreasedpotassiumAE/lab.abnorm.16.71.73.00.621.03.56.22.2CardiovascularMortality and MorbidityCV Death,MI,or HF(3096 events)0.000001N
12、oninferiorityVal Superior to CapCap Superior to ValNoninferiority not Demonstrated0.811.2Hazard Ratio(97.5%CI)1.13P-value(noninferiority)noninferiority marginCV Death(1657 events)0.001CV Death or HF(2661 events)0.0001CV Death or MI(2234 events)0.00001Favors ValsartanFavors CaptoprilCHARM-Preserved D
13、evelopment of new diabetes 47770.600.005(0.41-0.86)Number of casesHRp-valueCandesartanPlacebo(CI)Drugs Vasopressin receptor antagonists?Others?Devices External counterpulsation?Implantable hemodynamic monitors?CHARM-Preserved Development of new diabetes 47770.600.005(0.41-0.86)Number of casesHRp-val
14、ueCandesartanPlacebo(CI)MADIT II Patient Eligibility I.Prior myocardial infarction,II.andIII.EF 30%Exclusion Criteria:NYHA Class IV at enrollmentMI 1 monthCABG 3 monthsAdvanced organ system diseaseUnder age 21MADIT II Patient Eligibility I.Prior myocardial infarction,II.andIII.EF 30%Exclusion Criter
15、ia:NYHA Class IV at enrollmentMI 1 monthCABG 9 months NYHA Class I-IVUse of the ICD in Patients with Non-Ischemic Dilated CardiomyopathyPrimary Prevention Trial-DEFINITEMean QRS 116 ms No ICD ICDTotal deaths 33 222 yr mortality 14%8%p=.06Mortality risk reduction -34%Arrhythmic death risk reduction -
16、74%Kadish et al,AHA abstract,Nov,2003Endpoint:All-cause MortalityMortality Reduction with ICD TreatmentCP1108035-1%Overall deathArrhythmic deathAVIDCASHCIDSMADITMUSTT MADIT-II020406080100Conclusions is safe and well tolerated improves quality of life,functional class,and exercise capacity improves h
17、eart failure composite response may have a favorable effect on combined measures of morbidity and mortalityIn NYHA Class III and IV systolic heart failure patients with intraventricular conduction delays,cardiac resynchronization therapy:NEJM 2002;346:1845-53MIRACLEWorldwide ICD Implantation Rate pe
18、r YearCP1108035-3Year1980First Human implant1985FDA approval of ICDs1993Smaller devices1996Steroid leadsMADIT2000Cardiac resynchro-nizationICD implants(000s)1989Transvenous leadsBiphasic waveform1999MUSTT1988Tiered therapy1997/98DC ICDsAT therapiesAVIDCASHCIDSCHARM-Preserved:Primary outcome CV death
19、 or CHF hospitalisation0123years3.50102030PlaceboCandesartan51525HR 0.89(95%CI 0.77-1.03),p=0.118Adjusted HR 0.86,p=0.051%366(24.3%)333(22.0%)Use of the ICD in Patients with Non-Ischemic Dilated CardiomyopathyPrimary Prevention Trial-DEFINITEMean QRS 116 ms No ICD ICDTotal deaths 33 222 yr mortality 14%8%p=.06Mortality risk reduction -34%Kadish et al,AHA abstract,Nov,2003演讲完毕，谢谢观看！Thank you for reading!In order to facilitate learning and use,the content of this document can be modified,adjusted and printed at will after downloading.Welcome to download!汇报人：XXX 汇报日期：20XX年10月10日
