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

1、会计学1选择性醛固酮封锁需与瞬态或永久心脏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的急性心肌梗死住院期间衰竭患者EVENTAMI + CHF (%)AMI (%)Stroke 2.21.4A V block5.74.6VT or VF11.99.09Rupture/EMD1.81.0Unexpected cardiac arrest8.34.4LOS7.15.3Recurrent MI3.02.7Death21.47.2Cardiac Echo performed within 24 hrs after AMIACS = acute coronary syndromes

2、.Steg PG et al. Circulation. 2004;109:494-499.Time to Death Within 6 Months (n = 10,771)0.30.20.10.0012346HR = 3.8 (95% CI, 3.33 to 4.36)Heart failure at admissionNo heart failure at admissionProportion Dead5ACE-I = angiotensin-converting enzyme inhibitor; Ang I = angiotensin I; ARB = angiotensin II

3、 blocker.Alternative PathwaysAldosterone: Important Component of Renin-Angiotensin-Aldosterone SystemAdapted from Weber KT, Brilla CG. Circulation 1991;83:1849-1865.PlasmaHBP LVHFibrosisAngiotensin II Aldosterone Angiotensin IIAldosteroneAngiotensin IIAldosteroneYesYesYesYesYesYesYesYesNoHBP = high

4、blood pressure; LVH = left ventricular hypertrophy AldosteroneCardiac fibroblasts Collagen synthesis Collagen depositionMyocardial Fibrosis LV stiffnessLVDCHFAldosterone Receptor AntagonistsAdapted from Hameedi and Chadow. Curr Hypertens Rep. 2000;2:378-383VSMC = vascular smooth muscle cell; NO = ni

5、tric oxide; ET-1 = endothelin-1.Rajagopalan and Pitt. Med Clin North Am. 2003;87:441-457.McKelvie et al. Circulation 1999;100:1056-64 5040302010 0-20-10-30-40D D Aldosterone (pg/mL)17 weeks43 weeksCandesartan 4 mgCandesartan 8 mgCandesartan 16 mgCandesartan+ Enalapril 4 mg/20mgCandesartan+ Enalapril

6、 8 mg/20mgEnalapril 20 mgAldosterone Rebound Occurs Even with Combined ACE-I and AII Blocker (RESOLVD)11The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet. 1993;342:821-828. PlaceboRamiprilTime (months)353025201510500612182430HR 0.73 (95% CI, 0.60 to 0.89)P = .002Cumulative Mo

7、rtality (%)RR: 27%LV = left ventricular; HR = hazard ratio; RR = risk reduction.12HR = hazard ratio; RR = risk reduction.The CAPRICORN Investigators. Lancet. 2001;357:1385-1390.PlaceboCarvedilolProportion Event-FreeYears1.00.90.80.70.60.50.40.30.20.10.000.51.01.52.02.5HR 0.77 (95% CI, 0.60 to 0.98)P

8、 = .031RR:23%13Adapted from Pfeffer MA et al. N Engl J Med. 2003;349:1893-1906. Probability of Event0.40.30.20.10.0061218243036MonthsProbability of Event12Months0.40.30.20.10.00618243036CaptoprilValsartanValsartan and CaptoprilDeath From Any CauseCombined Cardiovascular Endpoint14Primary endpoints:S

9、econdary endpoints:Total mortalityCV mortality/CV hospitalizationsCV mortalityTotal mortality/total hospitalizationsEplerenone 25 to 50 mg qd(n = 3319)Placebo (n = 3313)6632 Patients 3 to 14 DaysPost-MI1012 DeathsPitt B et al. N Engl J Med. 2003;348:1309-1321.Acute MI, Heart Failure, LVEF 40%, Stand

10、ard TherapyRR:31%Pitt B et al. Abstract presented at: ESC Working Group on Acute Cardiac Care; 2004.EPHESUS Co-Primary Endpoint:Total Mortality (30 Days)Eplerenone + standard care Placebo + standard care Cumulative Incidence (%)Days From RandomizationHR = 0.69 (95% CI, 0.54 to 0.89)(4.6%)(3.2%)P = .

11、004HR = hazard ratio.RR = risk reduction.Adapted from Pitt B et al. N Engl J Med. 2003;348:1309-1321.Eplerenone + standard care (n = 3319)Placebo + standard care (n = 3313)Cumulative Incidence (%)2220181614121086420369121518212427Months Since RandomizationHR = 0.85 (95% CI, 0.75 to 0.96)P = .0080RR:

12、15%(16.7%)(14.4%)HR = hazard ratio.RR = risk reduction.HR = 0.87 (95% CI, 0.74 to 1.01)Pitt B et al. Abstract presented at: ESC Working Group on Acute Cardiac Care; 2004.RR:13%Eplerenone + standard carePlacebo + standard careCumulative Incidence (%)Days From Randomization(9.9%)(8.6%)HR = hazard rati

13、o.RR = risk reduction.P = .074Adapted from Pitt B et al. N Engl J Med. 2003;348:1309-1321.Eplerenone + standard care (n = 3319)Placebo + standard care (n = 3313)40Cumulative Incidence (%)35302520151050369121518212427HR = 0.87 (95% CI, 0.79 to 0.95)P = .0020Months Since RandomizationRR:13%(30.0%)(26.

14、7%)HR = hazard ratio.RR = risk reduction.Adapted from Pitt B et al. N Engl J Med. 2003;348:1309-1321.Eplerenone + standard care (n = 3319)Placebo + standard care (n = 3313)10Cumulative Incidence (%)86543210369121518212427HR = 0.79 (95% CI, 0.64 to 0.97)P = 0.03097Months Since RandomizationRR:21%HR =

15、 hazard ratio.RR = risk reduction.Eplerenonen (%)Placebon (%)P valueInvestigator reportedHyperkalemia113 (3.4%)66 (2.0%).001Hypokalemia15 (0.5%)49 (1.5%).001Laboratory assessed6.0 mEq/L180 (5.5%)126 (3.9%).0023.5 mEq/L273 (8.4%)424 (13.1%).001Pitt B et al. N Engl J Med. 2003;348:1309-1321.In-hospita

16、l TherapyDischarge TherapyLV = left ventricular; UFH = unfractionated heparin; LMWH = low-molecular-weight heparin; GP = glycoprotein; PCI = percutaneous coronary intervention.22Pitt B et al. N Engl J Med. 2003;348:1309-1321.2324EplerenonePlaceboMalesGynecomastia0.4%0.5% Mastodynia0.1%0.1%Females Ab

17、normal vaginal bleeding0.4%0.4%2526Serum Potassium (mEq/L)ActionDose Adjustment5.0Increase25 mg qod to 25 mg qd25 mg qd to 50 mg qd5.0-5.4MaintainNo adjustment5.5-5.9Decrease50 mg qd to 25 mg qd25 mg qd to 25 mg qod 25 mg qod to withhold6.0Withhold*Eplerenone can be restarted at 25 mg qod when the p

18、otassium level falls to 5.5 mmol/L)15.6%11.2%.001Incidence K (K+ 6.0 mmol/L)5.5%3.9%.002Study drug discontinuation due to K1%1%Deaths adjudicated to Kn = 0n = 1All deaths due to K + all sudden cardiac death + all deaths from unknown causes5.3%6.6%.016ACE-I = angiotensin-converting enzyme inhibitor;

19、Ang I = angiotensin I; ARB = angiotensin II blocker.Alternative PathwaysAldosterone: Important Component of Renin-Angiotensin-Aldosterone SystemMcKelvie et al. Circulation 1999;100:1056-64 5040302010 0-20-10-30-40D D Aldosterone (pg/mL)17 weeks43 weeksCandesartan 4 mgCandesartan 8 mgCandesartan 16 mgCandesartan+ Enalapril 4 mg/20mgCandesartan+ Enalapril 8 mg/20mgEnalapril 20 mgAldosterone Rebound Occurs Even with Combined ACE-I and AII Blocker (RESOLVD)In-hospital TherapyDischarge TherapyLV = left ve