acs治療原則

1、The Management of Acute Myocardial Infarction北京協(xié)和醫(yī)院急診科 朱華棟,Early Repolarization,Brugada Syndrome,Anterior AMI,Prinzmetal Angina,Pericarditis,Acute Inf. AMI,ST Segment Elevation (Transmural ischemia),Non-infarct ST E

2、levation,ST Segment Depression (Non-transmural ischemia),ST Depression NSTEMI,T wave inversion NSTEMI,NSTE ACS : Key Themes,NSTE ACS: a high risk population? patient risk ? ? benefit from treatment with medic

3、ations, an invasive strategyInteraction between invasive strategy and pharmacologic txAntithrombotics cornerstone of treatmentAnticoagulants: heparin, LMWH, direct thrombin inhibitorsAntiplatelet agents: aspirin, IIb

4、/IIIa, ADP inhibitors,,,Antman EM et al N Engl J Med 1996;335:1342-9,Invasive vs. Conservative Strategy for ACSDeath or (re)-MI,Trial N PCI ConsRITA 3 1810 7.6 8.3VINO

5、 131 6.3 22.4TACTICS 2220 7.3 9.5TRUCS 148 7.6 16.7FRISC II 2451 10.4 14.1MATE 201 9.9 6.7VANQUISH 920 24.0 12.2Overall 7876

6、,,,,,Fox, Lancet 360:743 ‘03,,Death/(re)-MI,CP971744-45,%,TACTICS–TIMI 18,TnT cut point = 0.01 ng/mL (54% of pt TnT +),Troponin T: Death, MI, Rehosp ACS, 6 Months,OR=0.52*P<0.001InteractionP<0.001,P=NS,*,n=4

7、14,n=396,n=463,n=495,,,Benefits of an Invasive Strategy in Non-ST Elevation ACS,,Only shown to reduce death and MI in high risk pts Reduces re-hospitalization, angina in many others Shortens hospitalization, may be

8、 cost effective What about the optimal timing of an invasive strategy?,,,Medical Tx for 72-170 hrThen, cath labn=207,,Cath lab ?6 hrn=203,ISAR-COOL,CP1107655-4,Neumann FJ et al JAMA 2004,,67% had ? troponin, 6

9、5% had ST depression,Aspirin500 mg, 100 mg bidClopidogrel600 mg, 75 mg bidTirofiban10 mg/kg bolus, 0.10 mg/kg/min infusionHeparin(PTT 60-85 seconds),,Non-ST? Acute Coronary Syndrome? troponin or ST depression

10、n=410,,ISAR-COOLPrimary Endpoint,CP1107655-2,30-day event rate (%),Death & MI,Death,Neumann FJ et al JAMA 2004,P=0.04,P=0.23,P=0.12,P=0.56,Any nonfatal MI,Nonfatal Q-wave MI,RR 1.96 (1.01-3.82),Cooling off (n=207

11、),Early intervention (n=203),,,Timing of an Invasive Strategy in Non-ST Elevation ACS,,ISAR-REACT was a small, single center study.Clinical trials are still going on. Other analyses also indicate that cath within

12、24 hours is better than later cath Ought to use intensive antiplatelet therapy with a very early invasive strategyWhat medical therapy ought to be used in ACS?,Antithrombotic Trialists’ Collaboration. BMJ. 2002;324:

13、71–86.,OR*,,,,,,,,,,0.5,1.0,1.5,2.0,500–1500 mg34 19160–325 mg19 2675–150 mg12 32<75 mg3 13Any aspirin65 23,Antiplatelet Better,Antiplatelet Worse,Aspirin DoseNo. of Trials(%),Odds Ratio,,0,,,,Asp

14、irin Dose and Events in High-Risk PtsFrequency of CV Death, MI, Stroke,P=0.0001,CURE,CP999547-2,Yusuf S et al NEJM 2001;16:494-502,Non-ST elevation ACS12,562 patients,ASA 75 to 325 mg po qdplacebon=6,303,3-12 month f

15、ollow-up(average 9 mo),ASA + clopidogrel(300 mg load, 75 mg qd)n=6,259,,,,CURECV Death/MI/Stroke, 1 Year,CP999731-3,CV death, MI, stroke (%),Clopidogrel (n=6,303),Placebo (n=6,259),P=0.00003,,Days after enrollment,CU

16、RE,Eventrate(%),RR 0.80P=0.00005,CP995058-6,CV death,MI, stroke,CVdeath,MI,Stroke,Non-CVdeath,RR 0.92P=NS,RR 0.77P<0.001,RR 0.85P=NS,RR 0.96P=NS,,,,CUREMajor/Life-Threatening Bleeds in the 7 Days After CAB

17、G,Major Bleeds: Significantly disabling, intraocular, or transfusion ?2 unitsLife Threatening: Hgb ? >5g/dl, hypotension (inotropes), surgery to stop bleeding, symptomatic ICH or transfusion ? 4 units,ACC/AHA ACS Gu

18、ideline Update,Class IAspirin 75 to 325 mg/day (level of evidence: A)ASA and clopidogrel for 9 months after NSTE ACS (level of evidence: B)Class 3Do not administer clopidogrel in the 5 days before CABG,Braunwald E, e

19、t al. www.acc.org,Heparin (UF or LMW) in ACS Without ST ?Death or MI,UFH or LMWH ControlOR95% CITheroux2/122 (1.6%)4/121 (3.3%)0.500.10-2.53Cohen0/371/32 (3.1%)0.120.01-5.89RISC3/210 (1.4%)7/189 (3.7%)

20、0.400.11-1.39Cohen4/105 (3.8%)9/109 (8.2%)0.460.15-1.41Holdright*42/154 (27.3%)40/131 (30.5%)0.850.51-1.43Gurfinkel4/70 (5.7%)7/73 (9.6%)0.580.17-1.98(UFH)Gurfinkel0/687/73 (9.6%)0.130.03-0.60(LMW

21、H)FRISC4/70 (5.7%)36/757 (4.8%)0.390.22-0.68UFH vs55/698 (7.9%)68/655 (10.4%)0.670.45-0.99placebo/controlLMWH vs13/809 (1.6%)43/830 (5.2%)0.340.20-0.58placeboTotal68/1507 (4.5%)104/1412 (7.4%)0.530.

22、38-0.73,Only RCTs, placebo or untreated controlsEikelboom JW et al: Lancet 55:1936-42, 2000,CP951342-1,,,,,,,,,,,,,,0.1Heparin better,1.0,10.0Control better,,,Trial: FRIC(dalteparin; n=1482)FRAXIS(nadroparin

23、; n=2357)ESSENCE(enoxaparin; n=3171)TIMI IIB(enoxaparin; n=3910),.751.01.5,,,?,?,,?,,?,(P=0.032),(P=0.029),Braunwald E et al.Circulation 2000;102:1193-1209,LMWHBetter,UFHBetter,LMWH versus UFH in UA/NSTEMI Manag

24、ed Non-invasively:Effect on Death, MI, Recurrent Ischemia,,CLASS Ia （Ia 級推薦）一旦出現(xiàn)UA/NSTEMI，需盡快在抗血小板治療的基礎(chǔ)上給予患者抗凝藥物。a. 介入方案：證據(jù)級別A-包括依諾肝素和普通肝素；證據(jù)級別B-包括比伐盧定和戊聚糖鈉b. 保守方案：藥物選擇可以是依諾肝素、普通肝素（證據(jù)級別A）或者戊聚糖鈉（證據(jù)級別B），有效性已經(jīng)確立。c.對于選擇

25、保守治療的病人，如果有較高的出血風(fēng)險，傾向于選擇戊聚糖鈉（證據(jù)級別B）CLASS IIa （IIa 級推薦）對于最初選擇保守治療策略的UA/NSTEMI病人，作為抗凝治療，依諾肝素或者戊聚糖鈉要優(yōu)于普通肝素，除非計劃在24小時內(nèi)進(jìn)行冠脈搭橋手術(shù)。（證據(jù)級別B）,2007年ACC/AHA UA/NSTEMI的指南抗凝治療推薦,ACC/AHA 2007更新的抗凝治療指南,高?；虼_診ACS實(shí)行導(dǎo)管或PCI,疑似/確診ACS,可能ACS,,

26、阿司匹林+IV UFH/LMWH*GP IIb/IIIa拮抗劑,阿司匹林+皮下 LMWH *或 IV UFH,氯吡格雷,氯吡格雷,阿司匹林,*證據(jù)等級Ia：依諾肝素優(yōu)于IV UFH,ACC/AHA 治療建議2007,“不穩(wěn)定型心絞痛/非ST段抬高心梗患者，除非計劃在24小時內(nèi)行冠脈搭橋手術(shù)，相對于普通肝素，依諾肝素（Enoxaparin）作為抗凝劑應(yīng)優(yōu)先選用。(證據(jù)級別 A )”,2002 update ACC/AHA gu

27、ideline,ACCP7指南對LMWH的治療建議,急性期LMWH優(yōu)于UFH（1B級）；LMWH治療時不需常規(guī)監(jiān)測（1C級）；已使用LMWH的患者如需進(jìn)行PCI，應(yīng)繼續(xù)使用LMWH（2C級）；應(yīng)用GPIIb/IIIa 受體拮抗劑者，LMWH安全性優(yōu)于UFH（2B級）。NSTE ACS 患者中LMWH的療程評價是：NSTE ACS患者應(yīng)早期介入治療，如果冠脈干預(yù)延遲，可考慮延長LMWH治療作為血運(yùn)重建的“橋梁”。,Rest pa

28、in > 5 min andST Δ > 0.1 mVorDocumented CADor? CK-MBN=132,,Heparin70 U/kg bolus+15 U/kg/hr infusion,Bivalirudin0.1 mg/kg bolus+0.25 mg/kg infusion,,,TIMI - 8: Bivalirudin vs. Placebo in ACS,TIMI - 8: B

29、ivalirudin vs. Placebo in ACS,4-6 wks,7 days,4-6 wks,7 days,p=0.008,p=0.024,p=NS,p=NS,,Beta Blockers,Reduce CV death, MI, stroke by 25-30% in high risk ptsNot well studied in non-STE ACSReduce heart rate, blood pressur

30、e, ischemia, chest discomfortClass 1 indication; quality indicatorUse in everyone without contraindications,Platelet GP IIb/IIIa Inhibition for Non-ST ? ACSPrimary Endpoint Results from the 5 Major RCTs,,All PCI trial

31、s17,3930.668.55.6All ACS trials24,3110.8912.811.4ACS troponin (+)1,3680.4216.36.9ACS PCI2,3110.6614.49.6ACS no PCI12,6850.9314.313.3ACS troponin (–)2,9011.056.26.5,IIb/IIIa Meta-Analysis30-D

32、ay Death, MI at 30 Days,CP944328- 1,RelativeriskPlaceboIIb/IIIaNo.ratio(%)(%),Chew DP et al: JACC 2000;36:2028 –35,,,,,,,,,,,,,IIb/IIIa better,Placebo better,IIb/IIIa Inhibitors in ACS Patients,Greatest bene

33、fit is during PCIIf pursuing a non-invasive strategy, recommend treating pts with elevated troponins, high TIMIscores, etc; probably those with diabetes, marked ST segment shiftsDo not recommend their routine administr

34、ation to all ACS pts in whom a non-invasive strategy is planned,Conclusions,Much remains to be learned about the optimal medical therapy for ACS ptsThe data favor an invasive strategy, and suggest different medications

35、and doses ought be administered if pursuing an invasive vs. non-invasive strategy, and in high vs. low risk pts,,UA / NSTEMI: Pharmacological and Mechanical Intervention,Braunwald E et al. J Am Coll Cardiol 2000;36:970-

36、1062Braunwald E et al. Circulation 2002;106:1893-1900,,,,,,Algorithm for Patients with UA/NSTEMI Managed by an Initial Invasive Strategy,Proceed to Diagnostic Angiography,ASA (Class I, LOE: A)Clopidogrel if ASA intoler

37、ant (Class I, LOE: A),Diagnosis of UA/NSTEMI is Likely or Definite,Invasive StrategyInitiate A/C Rx (Class I, LOE: A)Acceptable options: enoxaparin or UFH (Class I, LOE: A) bivalirudin or fondaparinux (Class I, LOE:

38、 B),Select Management Strategy,Proceed with an Initial Conservative Strategy,,Anderson JL. J Am Coll Cardiol. 2007, In press. Figure 7,,,,,,A,B,B1,B2,Prior to AngiographyInitiate at least one (Class I, LOE: A) or both

39、(Class IIa, LOE: B) of the following:ClopidogrelIV GP IIb/IIIa inhibitor,Factors favoring admin of both clopidogrel and GP IIb/IIIa inhibitor include:Delay to AngiographyHigh Risk FeaturesEarly recurrent ischemic d

40、iscomfort,,,,,,,Initiate clopidogrel (Class I, LOE: A) Consider adding IV eptifibatide or tirofiban (Class IIb, LOE: B),Conservative StrategyInitiate A/C Rx (Class I, LOE: A): Acceptable options: enoxaparin or UFH (Cl

41、ass I, LOE: A) or fondaparinux (Class I, LOE: B), but enoxaparin or fondaparinux are preferable (Class IIA, LOE: B),Select Management Strategy,ASA (Class I, LOE: A)Clopidogrel if ASA intolerant (Class I, LOE: A),Diagnos

42、is of UA/NSTEMI is Likely or Definite,Algorithm for Patients with UA/NSTEMI Managed by an Initial Conservative Strategy,Proceed with Invasive Strategy,(Continued),Anderson JL. J Am Coll Cardiol. 2007. In press. Figure 8,

43、,,,C2,C1,A,,Evidence for Primary PCI as Treatment of Choice for STEMI ACS,Summary of 23 Randomized Trials (n=7739),p=0.0003,p<0.0001,p=0.0004,p<0.0001OR=0.57,Keeley & Grines Lancet 2003,,,PCI,Lytic,Risk Reduc

44、tionDeath28%Death/MI/CVA43%,Primary PCI: The Preferred Reperfusion Strategy,Primary, Transfer, Facilitated & Rescue PCI for STEMI,Primary PCI (PPCI)Direct to CVL for PCI reperfusion therapyTransfer PCIP

45、ts transferred from hospitals without PCI facilities (no lysis) to a PCI centreFacilitated PCIPatients receiving thrombolysis* followed by intentional PCIRescue PCIPCI after failed thrombolysis (at 90 mins)*Thromb

46、olysis may be Pre-hospital,Door-To-Balloon (DTB) Time& Choice of Reperfusion Therapy in STEMI,Sx onset 60 minSx onset >3 hrs 12hr:No lysis but PCI may still be beneficial,Evidence for Pre-Hospital Thrombolysi

47、s for Early ( <2 Hour) STEMI,Evidence to support Transfer to PCI Centers from Hospitals without PCI facilities for STEMI ACS,Evidence Against Facilitated PCI for STEMI ACS,,Evidence for Resçue PTCA after faile

48、d fibrinolysis (RESCUE I trial),,,,,,,,,PTCA,,No PTCA,,P=0.001,,12,,6,,0,,62,,36,,24,,48,0.6,,0.7,,0.8,,0.9,1.0,,Time,(weeks),,,,Ellis, Am Heart J 2000; 139:1046,A.II.030,% Survival,Options for Patients with Prolonged Tr

49、ansfer Times,Full dose fibrinolytic with elective transfer or for rescueFull dose fibrinolytic with routine transfer and rescue as neededPrimary PCI (no matter how long it takes) Facilitated PCIAll of the above: Dep

50、ending on the time of day and which cardiologist is on call!,,2006 ESC Guidelines for STEMI,LATE RECANALIZATION OF INFARCT-RELATED ARTERY,BENEFITSRISKSPrevention of remodellingRisks of PCI& improved LV fun

51、ctionDecreased Vent. Arryhthm.Risk of RestenosisEnhance collaterals,ACS 臨床策略,體格檢查，ECG，實(shí)驗(yàn)室檢查,持續(xù)ST段抬高,非持續(xù)ST段抬高,診斷不明確,溶栓，PCI,肝素（LMWH，UFH），ASA，氯吡格雷，beta 阻滯劑，硝酸鹽,ASA,高危,低危,GP IIb/IIIa,冠脈造影,第2次肌鈣蛋白測定,陽性,兩次陰性,運(yùn)動試驗(yàn)，冠脈造影,