药物对心脏性猝死(SCD)的预防作用课件.ppt
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- 药物 心脏 猝死 SCD 预防 作用 课件
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1、The Role of Drugs in Prevention of Sudden Cardiac Death Weimin Li Professor of Medicine Cardiovascular Department,the First Clinical Hospital,Harbin Medical University,Harbin Presentation Overview Sudden Cardiac Death Epidemiology,etiology,pathophysiology Overview of ICD therapy to prevent SCD Roles
2、 of Drugs in SCD Prevention Summary and conclusionsEpidemiology of SCD Accounts for 63%of all cardiac related deaths in the US.One of the most common causes of death in developed countries:MMWR.Vol 51(6)Feb.15,2002.Myerberg RJ,Catellanos A.Cardiac Arrest and Sudden Cardiac Death.In:Braunwald E,ed.He
3、art Disease:A Textbook of Cardiovascular Medicine.5th Ed.New York:WB Saunders.1997:742-779.Zheng Z.Circulation.2001;104:2158-2163.Vreede-Swagemakers JJ et al.J Am Coll Cardiol 1997;30:1500-1505.WorldwideUS300,000350,0003,000,000W.Europe400,000Magnitude of SCD in China0.1%0.04%0.2%ChinaUS544,000300,0
4、00350,000ChinaUSIncidence RateAbsolute Number0.04%0.1%0.2%Incidence of SCD in Specific Populations Adapted from:Myerburg RJ.Sudden Cardiac Death:Exploring the Limits of Our Knowledge.J Cardiovasc Electrophysiol Vol.12,pp.369-381,March 2001.300,000200,000100,000Absolute number of SCD Per Year Multipl
5、e risk subgroupsPatients with any previous coronary eventPatients with ejectionfraction 35%or CHFCardiac arrest,VT/VF survivorsHigh-risk post-MI subgroupsGeneral adult population3025201050Incidence of SCD(%of group)MADIT II SCD-HeFT AVID,CASH,CIDS MADIT,MUSTT,nSudden death was the first manifestatio
6、n of coronary heart disease in 50%of men and 63%of women.nCHD accounts for at least 80%of sudden cardiac deaths in Western cultures.80%Coronary Heart Disease15%Cardiomyopathy5%Other Disease Cause of SCDAmerican Heart Association.Heart Disease and Stroke Statistics2003 Update.Dallas,Tex.:American Hea
7、rt Association;2002.Adapted from Heikki et al.N Engl J Med,Vol.345,No.20,2001.Myerberg RJ.Heart Disease,A Textbook of Cardiovascular Medicine.6th ed.P.895.Arrhythmic Cause of SCDAlbert CM.Circulation.2003;107:2096-2101.12%Other Cardiac Cause88%Arrhythmic CauseBradycardia16.5%VF62.4%Primary VT8.3%Tor
8、sades de Pointes12.7%Bays de Luna A.Am Heart J.1989;117:151-159.Application of ICD in China200544,000“Even the wealthiest nations cannot afford to pay to use every medical advance in any patient who might benefit.”Thomas Bigger,Lancet,2001Roles of Drugs in SCD PreventionRoles of Drugs in SCD Prevent
9、ionValue of Antiarrhythmic Drugs Class I antiarrhythmics Beta Blockers Amiodarone SotalolValue of Non-antiarrhythmic Drugs Electrolytes ACE inhibitors,ARBs and aldosterone blockers Antithrombotic and antiplatelet agents Statins n-3 Fatty acidsSCD Prevention by Antiarrhythmic DrugsAll-cause mortality
10、Days after randomization050100 150 200 250 300 350 400 450 500859095100Survival(%)Placebo(n=725)Encainide or flecainide(n=730):406CAST Investigators.N Engl J Med 1989;32112.P=0.000380 Roles of Class I antiarrhythmics in SCD PreventionCAST:Cardiac Arrhythmia Suppression TrialCAST II:Cardiac Arrhythmi
11、a Suppression Trial II As with the antiarrhythmic agents used in CAST-I,the use of moricizine in CAST-II to suppress asymptomatic or mildly symptomatic ventricular premature depolarizations to try to reduce mortality after myocardial infarction is not only ineffective but also harmful.Roles of Beta
12、Blockers in SCD PreventionStudyBHATNorwegianCOPERNICUSCIBIS-IICAPRICORNMERIT-HFPublished1981Follow upTarget Dosage(mg/day)Patientsmild/moderate HFPost-MI LVDPost-MI LVDPost-MI LVDmoderate/severe HFsevere HFDrugPropranoloTimololmetoprololcarvedilolbisoprololcarvedilol 200 qd 25 bid 10 bid 180240 25 b
13、id 10 qd25m17m15m2.4y1.3y10.4m19822000199919992001 Norwegian Multicentre Study Group.N Engl J Med.1981;304:801-807.36333027242118151296300.000.050.100.150.200.25TimololPlaceboMonthCumulative Mortality Raten=945n=939P0.0005Overview of Norwegian Timolol Trialand BHAT(Beta-Blocker Heart Attack)Trial (P
14、ost-MI LVD patients)39%Reduced mortality Placebo n=1921061824303612024681012N=383737063647395921631310406Cumulative Mortality(%)Months of Follow-upPropranolol n=1916P0.00526%Decreased mortalityBeta-Blocker Heart Attack Trial Research Group.JAMA.1982;247:1707-1714.BHATNorwegianAverage incidence of SC
15、D in long term trials comparing blockers with placebo after MINuttall SL,Toescu V,Kendall MJ.BMJ.2000;320:581.Average incidence of sudden death in long term trials comparing -blockers with placebo after myocardial infarction Placebo treatment Blocker treatment Norwegian timolol trialBlocker heart at
16、tack trialTotal No of patients 9391921Total No of deaths152188No(%)of sudden deaths95(63)89(47)Total No ofpatients 9451916Total No of deaths 98138No(%)of sudden deaths47(48)64(46)PlaceboCarvedilolHazard Ratio(95%CI)Cardiovascular Death1391040.75(0.58-0.96)Sudden Death69510.74(0.51-1.06)Death Due to
17、Pump Failure30180.60(0.33-1.07)CAPRICORN:Carvedilol Post-Infarct Survival Control in LV Dysfunction -TRIAL RESULTS-Dargie HJ et al.Eur J Heart Fail.2000;2:325-332.CIBIS II:Cardiac Insufficiency Bisoprolol Study II -RESULTS-PPrimary endpoint All-cause mortality Secondary endpoints All-cause hospital
18、admission All cardiovascular deaths Combined endpoint Exploratory analyses Sudden death Hospital admission for worsening heart failure17 39 12 35 6 1812 33 9 29 4 120.66(0.54 0.81)0.80(0.71 0.91)0.71(0.56-0.90)0.79(0.69 0.90)0.56(0.39-0.80)0.64(0.53 0.79)0.0001 0.0006 0.0049 0.0004 0.0011 0.0001Prim
19、ary and secondary outcomesPlacebo(n=1320)(%)(n=1327)(%)Hazard ratio(95%CI)CIBIS-II Investigators and Committees.Lancet 1999;353MERIT-HF:Metoprolol CR/XL Randomized Intervention Trial in congestive Heart Failure -RESULTS-MERIT-HF Study Group.Lancet 1999;353:20017.00.51.01.5Relative risk for mortality
20、Relative risk(95%CI)MortalityMetoprolol CR/XL betterRiskreduction(%)Total mortalityCardiovascular mortalitySudden deathDeath from worseningheart failure343841490.00620.000030.00020.0023PCOPERNICUS:Carvedilol Prospective Randomized Cumulative Survival trial-SUMMARY-In patients with severe chronic hea
21、rt failure,carvedilol in addition to standard therapy reduced:l All-cause mortalityl Combined endpoint of all-cause mortality and hospitalization for any reasonPacker M,Coats AJ,Fowler MB et al.N Engl J Med 2001;344:16518.Roles of Beta Blockers in SCD PreventionStudyBHATNorwegianCOPERNICUSCIBIS-IICA
22、PRICORNMERIT-HFSCD Risk Reduction(p-value)DrugPropranoloTimololmetoprololcarvedilolbisoprololcarvedilolTotal Death Risk Reduction(p-value)34%(0.00009)23%(0.031)26%(0.005)39%(0.0005)35%(0.001)34%(0.0001)Not reportedNot reported26%(0.099)41%(0.0002)44%(0.001)Not reported Roles of Amiodarone in SCD Pre
23、ventionConnolly SJ.Meta-analysis of antiarrhythmic drug trials.Am J Cardiol 1999;84:90R3R.A meta-analysis of effects of amiodarone on SCD Meta-analysis of effects of amiodarone on SCD-RESULTS-Cumulative risk of total mortality and arrhythmic/sudden death from a meta-analysisof 13 trials of amiodaron
24、eAmiodaroneControlTotal mortalityArrhythmic/sudden death29%reduction inarrhythmic deathP=0.0003Meta-analysis of the ICD secondary prevention trialsConnolly SJ.et al.Meta-analysis of the implantable cardioverter defibrillator secondary prevention trialsEuropean Heart Journal.2000;20712078Meta-analysi
25、s of effects of amiodarone on SCD -RESULTS-Cumulative risk of fatal events or the amiodarone and treatment arms.Hazard ratio:0.73P0.001Hazard ratio:0.49P35%and 35%The efficacy of the ICD over amiodarone appears to be dependent upon the degree of left ventricular dysfunction.MortalityFolow-up(m)Morta
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