选择性醛固酮封锁需与瞬态或永久心脏的急性心肌梗死住院期间衰竭患者.ppt
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1、Need for Selective Aldosterone Blockade for Patients with Transient or Persistent Heart Failure During Hospitalisation for AMI,Professor C Richard CONTI University of Florida College of Medicine, Gainsville, Florida (USA),Hospital Events in NRMI AMI Patients,AMI and HF,Conclusions from NMRI CHF and
2、AMI is a high risk situation Despite the high risk, these patients are less frequently treated with medications with proven mortality benefit or with primary reperfusion strategies None of these patients were treated with aldactone or eplerenone,Cardiac Echo performed within 24 hrs after AMI,Prognos
3、is after Myocardial Infarction,GRACE: Impact of Heart Failure on Cumulative Mortality From ACS,ACS = acute coronary syndromes. Steg PG et al. Circulation. 2004;109:494-499.,Time to Death Within 6 Months (n = 10,771),0.3,0.2,0.1,0.0,0,1,2,3,4,6,HR = 3.8 (95% CI, 3.33 to 4.36),Heart failure at admissi
4、on No heart failure at admission,Proportion Dead,5,ACE-I = angiotensin-converting enzyme inhibitor; Ang I = angiotensin I; ARB = angiotensin II blocker.,Pathophysiologic effects on cardiovascular system,Ang II,Ang I,Angiotensinogen,Renin,Na+/H2O retention K+, Mg+ loss,Aldosterone,ACE,ACE-i,Non-RAAS
5、Stimulators,ARB,ARB,Aldosterone Blockers,Aldosterone,Non-RAAS stimulators,Alternative Pathways,Aldosterone: Important Component of Renin-Angiotensin-Aldosterone System,Fibrosis,Fibrosis,No fibrosis,Adapted from Weber KT, Brilla CG. Circulation 1991;83:1849-1865.,Unilateral Renal Artery Stenosis,Aldo
6、sterone Infusion in Uninephric Rat,Infrarenal Aortic Banding,Plasma,HBP,LVH,Fibrosis,Angiotensin II Aldosterone Angiotensin II Aldosterone Angiotensin II Aldosterone,Yes,Yes,Yes,Yes,Yes,Yes,Yes,Yes,No,HBP = high blood pressure; LVH = left ventricular hypertrophy,Aldosterone Stimulates Myocardial Fib
7、rosis,Myocardial Fibrosis in Hypertension and CHF: The Aldosterone Hypothesis, Aldosterone,Cardiac fibroblasts, Collagen synthesis, Collagen deposition,Myocardial Fibrosis, LV stiffness,LVD,CHF,Aldosterone Receptor Antagonists,Adapted from Hameedi and Chadow. Curr Hypertens Rep. 2000;2:378-383,Patho
8、physiologic Mechanisms of Aldosterone in Heart Failure,VSMC = vascular smooth muscle cell; NO = nitric oxide; ET-1 = endothelin-1. Rajagopalan and Pitt. Med Clin North Am. 2003;87:441-457.,Adrenal,Myocardial/Vascular,Angiotensin II, K+, ACTH, Aldosterone, Fibroblast Collagen Synthesis,VSMC Hypertrop
9、hy, Free Radical Production, NO (in adrenal), AT1R Binding of Ang II, ACE Activity, PAI-1, ET-1,McKelvie et al. Circulation 1999;100:1056-64,50,40,30,20,10,0,-20,-10,-30,-40,D Aldosterone (pg/mL),17 weeks,43 weeks,Candesartan 4 mg,Candesartan 8 mg,Candesartan 16 mg,Candesartan + Enalapril 4 mg/20mg,
10、Candesartan + Enalapril 8 mg/20mg,Enalapril 20 mg,Aldosterone Rebound Occurs Even with Combined ACE-I and AII Blocker (RESOLVD),11,AIRE: ACE Inhibition for Post-MI LV Dysfunction,The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet. 1993;342:821-828.,Placebo Ramipril,RR: 27%,LV
11、= left ventricular; HR = hazard ratio; RR = risk reduction.,12,CAPRICORN: Beta-blockade for Post-MI LV Dysfunction (Only Event-free for All-cause Mortality),HR = hazard ratio; RR = risk reduction. The CAPRICORN Investigators. Lancet. 2001;357:1385-1390.,Placebo,Carvedilol,Proportion Event-Free,Years
12、,1.0,0.9,0.8,0.7,0.6,0.5,0.4,0.3,0.2,0.1,0.0,0,0.5,1.0,1.5,2.0,2.5,HR 0.77 (95% CI, 0.60 to 0.98) P = .031,RR: 23%,13,VALIANT: ARB and/or ACEI Post MI,Adapted from Pfeffer MA et al. N Engl J Med. 2003;349:1893-1906.,Probability of Event,0.4,0.3,0.2,0.1,0.0,0,6,12,18,24,30,36,Months,Probability of Ev
13、ent,12,Months,0.4,0.3,0.2,0.1,0.0,0,6,18,24,30,36,Captopril,Valsartan,Valsartan and Captopril,Death From Any Cause,Combined Cardiovascular Endpoint,14,EPHESUS: Study Design,Primary endpoints:,Secondary endpoints:,Total mortality CV mortality/CV hospitalizations CV mortality Total mortality/total hos
14、pitalizations,Eplerenone 25 to 50 mg qd (n = 3319),Placebo (n = 3313),6632 Patients 3 to 14 Days Post-MI 1012 Deaths,Pitt B et al. N Engl J Med. 2003;348:1309-1321.,Acute MI, Heart Failure, LVEF 40%, Standard Therapy,RR: 31%,Pitt B et al. Abstract presented at: ESC Working Group on Acute Cardiac Car
15、e; 2004.,EPHESUS Co-Primary Endpoint: Total Mortality (30 Days),Eplerenone + standard care,Placebo + standard care,Cumulative Incidence (%),Days From Randomization,HR = 0.69 (95% CI, 0.54 to 0.89),(4.6%),(3.2%),P = .004,HR = hazard ratio. RR = risk reduction.,EPHESUS Co-Primary Endpoint: Total Morta
16、lity (Duration of Study),Adapted from Pitt B et al. N Engl J Med. 2003;348:1309-1321.,Eplerenone + standard care (n = 3319),Placebo + standard care (n = 3313),RR: 15%,(16.7%),(14.4%),HR = hazard ratio. RR = risk reduction.,HR = 0.87 (95% CI, 0.74 to 1.01),EPHESUS Co-Primary Endpoint: CV Mortality/CV
17、 Hospitalization (30 Days),Pitt B et al. Abstract presented at: ESC Working Group on Acute Cardiac Care; 2004.,RR: 13%,Eplerenone + standard care,Placebo + standard care,Cumulative Incidence (%),Days From Randomization,(9.9%),(8.6%),HR = hazard ratio. RR = risk reduction.,P = .074,EPHESUS Co-Primary
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- 关 键 词:
- 选择性 醛固酮 封锁 瞬态 永久 心脏 急性 心肌梗死 住院 期间 衰竭 患者
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