急性心肌梗塞的溶栓治疗课件.ppt

1、Unfractionated heparinEnoxaparinUnfractionated heparinEnoxaparinAbciximabAbciximabNoneNoneENTIREACC/AHA heparin doseLow-dose heparinEnoxaparinNoneAbciximabNoneASSENT-3Standard-dose heparinLow-dose heparinNoneAbciximab50%TNK-tPA50%TNK-tPA100%TNK-tPA100%TNK-tPA100%TNK-tPA50%TNK-tPA100%TNK-tPA100%r-PA5

2、0%r-PAGUSTO-VAnticoagulantGP IIb/IIIaReceptor InhibitorLyticTrialLow-dose heparinLow-dose heparinLow-dose heparinEptifibatideEptifibatideEptifibatide50%TNK-tPA75%TNK-tPA100%TNK-tPAINTEGRITILow-dose heparinLow-dose heparinLow-dose heparinTirofibanTirofibanTirofiban50%TNK-tPA75%TNK-tPA100%TNK-tPAFASTE

3、RAnticoagulantGP IIb/IIIaReceptor InhibitorLyticTrial03050604020%TIMI Grade 3 Flowt-PASK10t-PA5SK876040801006020%Patients With TIMI Grade 3 FlowGUSTO-I90 minT14 t-PA90 minT14 r-PA90 minSPEED60-90 minINTRO-AMI60 minPooled60-90 min5473704740567873545664Lytic aloneCombination There was a 7.4%improvemen

4、t in the rate of TIMI Grade 3 flow If a 20%improvement is required to improve mortality by 1%,then a 7.4%improvement would be predicted to improve mortality by 0.3%04080100r-PA 10+10 Ur-PA 5+5 U+Abx6020Patency(%)TIMI-2TIMI-3The GUSTO-V Investigators.Lancet.2019;357:1905-1914.ST ,lytic eligible,6 h(n

5、=16,588)ASANo Abciximab2 x 10 U bolus(30)Full-dose r-PA AbciximabLow-dose Heparin:60 U/kg bolus followed by 7 U/kg/h infusion1 end point:mortality at 30 days2 end point:clinical and safety events at 30 days2 x 5 U bolus(30)Half-dose r-PAStandard Heparin:5000 U bolus followed by800 U/h(80 kg)or 1000

6、U/h(80 kg)infusionThe GUSTO-V Investigators.Lancet.2019;357:1905-1914.0%MortalityDays051015202530P=.43 for superiorityNon-Inferiority RR 0.95(95%CI,0.84-1.08)Std.Reteplase(n=8260)Abx+Dose Reteplase(n=8328)4625.9%5.6%Adapted with permission from the GUSTO-V Investigators.Lancet.2019;357:1905-1914.Non

7、-Inferiority RR 0.95(95%CI,0.84-1.08)OR and 95%CIThe GUSTO-III Investigators.N Engl J Med.2019;337:1118-1123.The GUSTO-V Investigators.Lancet.2019;357:1905-1914.037851264GUSTO IIIGUSTO V7.4%5.9%DeathP.00104050203010GUSTO IIIGUSTO V48%37%Anterior MI00.50.91.00.70.30.40.80.60.2GUSTO IIIGUSTO V0.91%0.5

8、9%ICHP=.0150.10.21.21.72.3*Unblinded,unadjudicatedThe GUSTO-V Investigators.Lancet.2019;357:1905-1914.01342Myocardial Infarction(%)AnyQ-waveEnzymaticIschemic STChange*3.50.51.62.7r-PAr-PA+AbxP 70 yrs 75 yrs 75 yrs0.41.20.51.11.50.42.1r-PA(n=8260)r-PA+Abx(n=8328)0.3P=.66P=.53P=.27*P=.069*P.0001.The G

9、USTO-V Investigators.Lancet.2019;357:1905-1914.01525302010PCI(%)UrgentThrough Day 75r-PAr-PA+Abx2.89.05.4Heartwire News.September 2,2019.GUSTO-V:Combination half-dose fibrinolytic plus IIb/IIIa blocker.An Alternative approach to MI?6.74.89.60410128Myocardial Infarction(%)r-PAr-PA+Abxn=1173DeathRepea

10、t MIDeath Plus Repeat MI26 Compared with r-PA monotherapy,combination therapy with r-PA and abciximab resulted in A mortality rate that was not inferior to r-PA monotherapy Fewer nonfatal reinfarctions(primarily a reduced incidence of recurrent ST elevation)A lower rate of urgent revascularization M

11、ore noncerebral bleeding complications,transfusions,and thrombocytopenia A higher rate of ICH in elderly patients over the age of 75 years TNK-tPA plus enoxaparin Favorable effects of LMWHs in recent small-scale thrombolysis trials Higher late patency:HART-2ASSENT-PlusAMI-SK Less reocclusion:HART-2

12、Fewer reinfarctions:ASSENT-PlusAMI-SKWilson,et al.ASSENT-3 is the first large-scale trial to test LMWHST-Segment Elevation AMI(n=6095 patients)150 to 325 mg ASA(daily)RandomizedFull-dose TNK-tPAPlus EnoxaparinHalf-dose TNK-tPAPlus AbciximabPlus Low-dose HeparinFull-dose TNK-tPAPlus Weight-adjusted U

13、FHThe ASSENT-3 Investigators.Lancet.2019;358:605-613.Primary Efficacy End Point:Composite of 30-day mortality or in-hospital reinfarction or in-hospital refractory ischemia.Primary Efficacy Plus Safety End Point:Composite of 30-day mortality or in-hospital reinfarction or in-hospital refractory isch

14、emia plus in-hospital intracranial haemorrhage or in-hospital major bleeding other than intracranial.05101520%Risk of 30-Day D/MI/Ref IschTNK-tPA+EnoxTNK-tPA+AbxTNK-tPA+UFH*P-values are the Bonferroni P-values after correcting for multiple comparisons.The uncorrected P-values were P=.0002 for the en

15、ox vs UFH comparison,and P.0001 for the abx vs UFH comparison.11.411.115.43-way P=.0001P=.0002*P=.0009*%Risk of 30-Day D/MI/Ref Isch/Maj Bleed/ICH*P-values are the Bonferroni P-values after correcting for multiple comparisons.The uncorrected P-values were P=.0037 for the enox vs UFH comparison,and P

16、=.0142 for the abx vs UFH comparison.05101520TNK-tPA+EnoxTNK-tPA+AbxTNK-tPA+UFH13.814.217.03-way P=.0062P=.0057*P=.0146*UFHAbx*51015202530024681012141620180Enox*log-rank P=.0001*vs UFHDays to death,reinfarction,orrefractory ischemiaPrimary Efficacy End PointProbability(%)Reprinted with permission fr

17、om the ASSENT-3 Investigators.Lancet.2019;358:605-613.51015202530024681012141620180log-rank P=.0062*vs UFH+AbxDays to death,reinfarction,refractoryischemia,ICH,or major bleedingPrimary Efficacy PlusSafety End PointProbability(%)UFHAbxEnox*There was a statistically significant interaction between tre

18、atment with abciximab and age such that patients over the age of 75 had poorer outcomes with abciximab(P=.001).%Risk of 30-Day Efficacyand Safety End Point015253545TNK-tPA+EnoxTNK-tPA+AbxTNK-tPA+UFH25.536.928.0P=.001*520304010*There was a statistically significant interaction between treatment with

19、abciximab and diabetes,such that diabetics had poorer outcomes with abciximab therapy(P=.0007).%Risk of 30-Day Efficacyand Safety End Point0152530TNK-tPA+EnoxTNK-tPA+AbxTNK-tPA+UFH13.922.316.5P=.007*5201004810TNK-tPA+EnoxTNK-tPA+AbxTNK-tPA+UFH5.46.66.03-way P=.2562%Risk of 30-Day Mortality%Risk of 3

20、0-Day Death or MI04810TNK-tPA+EnoxTNK-tPA+AbxTNK-tPA+UFH6.87.39.13-way P=.019862%Risk of In-HospitalRecurrent MI0245TNK-tPA+EnoxTNK-tPA+AbxTNK-tPA+UFH2.72.24.23-way P=.000931%Risk of 30-DayRefractory Ischemia04810TNK-tPA+EnoxTNK-tPA+AbxTNK-tPA+UFH4.63.26.53-way P.000162*While 3-way P-value is signif

21、icant,Enox vs UFH comparison P=NSEnoxAbxUFHP-Value(n=2040)(n=2019)(n=2038)3-wayAny thrombocytopenia1.23.21.3.0001Thrombocytopenia.000120,000 cells/L0.10.50.220,000 to 50,000 cells/L0.20.60.250,000 to 100,000 cells/L0.92.01.0Bleeding episodesTotal25.6*39.721.1.0001Major3.0*4.32.2.0005Minor22.6*35.418

22、.8.0001Blood transfusion3.4*4.22.3.0032*Including hemorrhagic conversionUnclassifiedHemorrhagic conversionIschemic stroke*Intracranial hemorrhageTotal strokes0.150.150.070.070.400.640.940.881.491.62Abx(n=2019)Enox(n=2040)0.590.050.770.000.570.540.980.930.941.52P-ValueUFH(n=2038)ASSENT-3:In-Hospital

23、PCIGUSTO-V:Urgent PCI057863Mortality(%)4212.53.72.75.46.7TNK-tPA+EnoxTNK-tPA+AbxTNK-tPA+UFHr-PA+UFHr-PA+AbxReprinted with permission from Cannon CP,et al.J Am Coll Cardiol.2019;37:323A.Correlation Between Estimated and Actual Patient Weight in TIMI 10B40.536.4188.5Actual Patient Weight(kg)Estimated

24、Patient Weight(kg)R2=0.93,P.0001181 Errors in estimating weight are uncommon,especially those that would lead to a dose change(1.3%or 49/3730 for TNK-tPA and 4.5%or 13/290 for t-PA).No adverse outcomes were seen among patients who received an incorrect dose,suggesting a broad safety profile for the

25、new single-bolus agent TNK-tPA.Cannon CP,et al.J Am Coll Cardiol.2019;37:323A.“The results obtained with half-dose tenecteplase plus abciximab are very similar to those with half-dose reteplase and abciximab seen in GUSTO-V.”“In both trials,these benefits are obtained at the cost of a higher rate of

26、 major bleeding complications and blood transfusions.”“No benefit and perhaps even harm was observed in patients above 75 years and in diabetics.”“Taken together they suggest that caution should be exercised regarding the use of conjunctive therapy with abciximab in elderly patients with an acute my

27、ocardial infarction treated with a fibrinolytic agent.”The ASSENT-3 Investigators.Lancet.2019;358:605-613.“In view of the present data and the ease of administration,enoxaparin might be considered an attractive alternative anticoagulant treatment when given in combination with tenecteplase.”The ASSE

28、NT-3 Investigators.Lancet.2019;358:605-613.ST MI 6h(n=461)UFH60 U/kg bolus12 U/kg/h infusion 36 h ENOXvarying doses+/-IV bolusIndex Hosp(8 d)ASA ENOXvarying doses+/-IV bolusIndex Hosp(8 d)Combination Reperfusion:Half-dose TNK-tPA+Abx(0.27 mg/kg)Standard Reperfusion:Full-dose TNK-tPA(0.53 mg/kg)Antma

29、n E,et al.Eur Heart J.2019;22:15.Abstract 145.UFH 40 U/kg bolus7 U/kg/h infusion 36 h Should enoxaparin replace UFH as the optimal antithrombin agent for AMI?Will similar improvements in efficacy and safety occur if enoxaparin is combined with a less fibrin-specific agent such as r-PA?Will physician

30、s accept the use of enoxaparin in selected patients with ST-elevation MI who may require rescue PCI?Will trials of TNK-tPA plus the small molecule GP IIb/IIIa receptor inhibitors produce results similar to ASSENT-3?What is the optimal strategy for facilitated PCI?Large embolii:Filters Small embolii(

31、thrombii):Filters&GP IIb/IIIa inhibitors,p-selectin inhibitors Vasoconstrictor release:GP IIb/IIIa inhibitors Spasm:Adenosine,Ca channel blockers,alpha blockers,avoid over sizing with PCI,high pressure inflations,serotonin inhibitors,endothelin inhibitors Endothelial&Myocardial swelling:Myocardial cooling,Ca channel blockers,DHEA,Na/H pump inhibitors,anti-inflammatory approaches