1、ACS治療原則ACS治療原則Early RepolarizationBrugada SyndromeAnterior AMIPrinzmetal AnginaPericarditisAcute Inf. AMIST Segment Elevation (Transmural ischemia)Non-infarct ST ElevationACS治療原則2Early RepolarizationBrugada SyST Segment Depression (Non-transmural ischemia)ST Depression NSTEMIT wave inversion NSTEMIA

2、CS治療原則3ST Segment Depression (Non-traACS治療原則4ACS治療原則4NSTE ACS : Key ThemesNSTE ACS: a high risk population patient risk benefit from treatment with medications, an invasive strategyInteraction between invasive strategy and pharmacologic txAntithrombotics cornerstone of treatmentAnticoagulants: hepar

3、in, LMWH, direct thrombin inhibitorsAntiplatelet agents: aspirin, IIb/IIIa, ADP inhibitorsACS治療原則5NSTE ACS : Key ThemesNSTE ACS:Antman EM et al N Engl J Med 1996;335:1342-9ACS治療原則6ACS治療原則6Invasive vs. Conservative Strategy for ACSDeath or (re)-MITrial N PCI ConsRITA 3 1810 7.6 8.3VINO 131 6.3 22.4TA

4、CTICS 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 7876Fox, Lancet 360:743 03Death/(re)Infarction RR= 0.88, p=0.05Intervention better 0.1 0.2 0.3 0.5 0.7 1.0 1.5 2.0Death/(re)-MIACS治療原則7Invasive vs. Conservative StraCP971744-45 %Cons InvTACTICSTI

5、MI 18TnT cut point = 0.01 ng/mL (54% of pt TnT +) Troponin T: Death, MI, Rehosp ACS, 6 MonthsOR=0.52*P0.001InteractionP0.001P=NS*n=414n=396n=463n=495ACS治療原則8CP971744-45 %Cons InvTACTICSTBenefits of an Invasive Strategy in Non-ST Elevation ACS Only shown to reduce death and MI in high risk pts Reduce

6、s re-hospitalization, angina in many others Shortens hospitalization, may be cost effective What about the optimal timing of an invasive strategy?ACS治療原則9Benefits of an Invasive StrateMedical Tx for 72-170 hrThen, cath labn=207Cath lab 6 hrn=203ISAR-COOLCP1107655-4Neumann FJ et al JAMA 200467% had t

7、roponin, 65% had ST depressionAspirin500 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 depressionn=410ACS治療原則10Medical Tx for 72-170 hrCath lISAR-COOLPrimary EndpointCP1107655-230-day

8、event rate (%)Death & MIDeathNeumann FJ et al JAMA 2004P=0.04P=0.23P=0.12P=0.56Any nonfatal MINonfatal Q-wave MIRR 1.96 (1.01-3.82)Cooling off (n=207)Early intervention (n=203)ACS治療原則11ISAR-COOLPrimary EndpointCP11Timing of an Invasive Strategy in Non-ST Elevation ACS ISAR-REACT was a small, single

9、center study.Clinical trials are still going on. Other analyses also indicate that cath within 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? ACS治療原則12Timing of an Invasive StrategyAntith

10、rombotic Trialists Collaboration. BMJ. 2002;324:7186. OR*0.51.01.52.05001500 mg34 19160325 mg19 2675150 mg12 3275 mg3 13Any aspirin65 23Antiplatelet BetterAntiplatelet WorseAspirin DoseNo. of Trials(%)Odds Ratio0Aspirin Dose and Events in High-Risk PtsFrequency of CV Death, MI, StrokeP=0.0001ACS治療原則

11、13 OR*0.51.01.52.05001500 mCURECP999547-2Yusuf S et al NEJM 2001;16:494-502Non-ST elevation ACS12,562 patientsASA 75 to 325 mg po qdplacebon=6,3033-12 month follow-up(average 9 mo)ASA + clopidogrel(300 mg load, 75 mg qd)n=6,259ACS治療原則14CURECP999547-2Yusuf S et al NECURECV Death/MI/Stroke, 1 YearCP99

12、9731-3CV death, MI, stroke (%)Clopidogrel (n=6,303)Placebo (n=6,259)P=0.00003Days after enrollmentACS治療原則15CURECV Death/MI/Stroke, 1 YeaCUREEventrate(%)RR 0.80P=0.00005CP995058-6CV death,MI, strokeClopidogrel (n=6,259)Placebo (n=6,303)Aspirin andCVdeathMIStrokeNon-CVdeathRR 0.92P=NSRR 0.77P0.001RR 0

13、.85P=NSRR 0.96P=NSACS治療原則16CUREEventrate(%)RR 0.80CP995CUREMajor/Life-Threatening Bleeds in the 7 Days After CABGPlaceboClopRRpStopped 5g/dl, hypotension (inotropes), surgery to stop bleeding, symptomatic ICH or transfusion 4 unitsACS治療原則17CUREMajor/Life-Threatening BACC/AHA ACS Guideline UpdateClas

14、s 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 CABGBraunwald E, et al. ACS治療原則18ACC/AHA ACS Guideline UpdateClHeparin (UF or LMW) in ACS Without ST Death or MI UFH or LM

15、WH 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%)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

16、%)0.130.03-0.60(LMWH)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%)0.530.38-0.73Only RCTs, placebo or untreated controlsEikelboom JW et al: Lancet 55:1936-4

17、2, 2000CP951342-10.1Heparin better1.010.0Control betterACS治療原則19Heparin (UF or LMW) in ACS WitTrial: FRIC(dalteparin; n=1482)FRAXIS(nadroparin; 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;102:1193-1209LMWHBetterUFHBetter

18、LMWH versus UFH in UA/NSTEMI Managed Non-invasively:Effect on Death, MI, Recurrent IschemiaACS治療原則20Trial: .751.01.5(P=0CLASS Ia （Ia 級推薦）一旦出現UA/NSTEMI，需盡快在抗血小板治療的基礎上給予患者抗凝藥物。a. 介入方案：證據級別A-包括依諾肝素和普通肝素；證據級別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（證據級別A）或者戊聚糖鈉（證據級別B），有效性已經確立。c.對于選擇保守治療的病人，如果有較高的出血風險，傾向于選擇

19、戊聚糖鈉（證據級別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于普通肝素，除非計劃在24小時內進行冠脈搭橋手術。（證據級別B）2007年ACC/AHA UA/NSTEMI的指南抗凝治療推薦ACS治療原則21CLASS Ia （Ia 級推薦）2007年ACC/AHA ACC/AHA 2007更新的抗凝治療指南高危或確診ACS實行導管或PCI 疑似/確診ACS 可能ACS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*證據等級Ia

20、：依諾肝素優于IV UFHACS治療原則22ACC/AHA 2007更新的抗凝治療指南高危或確診ACS實ACC/AHA 治療建議2007 “不穩定型心絞痛/非ST段抬高心?；颊撸怯媱澰?4小時內行冠脈搭橋手術，相對于普通肝素，依諾肝素（Enoxaparin）作為抗凝劑應優先選用。(證據級別 A )”2002 update ACC/AHA guidelineACS治療原則23ACC/AHA 治療建議2007 “不穩定型心絞痛/非SACCP7指南對LMWH的治療建議急性期LMWH優于UFH（1B級）；LMWH治療時不需常規監測（1C級）；已使用LMWH的患者如需進行PCI，應繼續使用LMWH（

21、2C級）；應用GPIIb/IIIa 受體拮抗劑者，LMWH安全性優于UFH（2B級）。NSTE ACS 患者中LMWH的療程評價是：NSTE ACS患者應早期介入治療，如果冠脈干預延遲，可考慮延長LMWH治療作為血運重建的“橋梁”。 ACS治療原則24ACCP7指南對LMWH的治療建議急性期LMWH優于UFH（Rest pain 5 min andST 0.1 mVorDocumented CADor CK-MBN=132Heparin70 U/kg bolus+15 U/kg/hr infusion Bivalirudin0.1 mg/kg bolus+0.25 mg/kg infusion

22、TIMI - 8: Bivalirudin vs. Placebo in ACSACS治療原則25Rest pain 5 min andHeparinBiTIMI - 8: Bivalirudin vs. Placebo in ACS4-6 wks7 days4-6 wks7 daysp=0.008p=0.024p=NSp=NSACS治療原則26TIMI - 8: Bivalirudin vs. PlacACS治療原則27ACS治療原則27Beta BlockersReduce CV death, MI, stroke by 25-30% in high risk ptsNot well st

23、udied in non-STE ACSReduce heart rate, blood pressure, ischemia, chest discomfortClass 1 indication; quality indicatorUse in everyone without contraindicationsACS治療原則28Beta BlockersReduce CV death, 15.75.617.911.712.814.23.812.910.311.805101520Primary Endpoint %PlaceboGP IIb/IIIaPURSUIT30 daysPRISM4

24、8 hrsPRISM PLUS7 daysP = 0.04P = 0.01P = 0.004PARAGON A30 daysP = 0.48PARAGON B30 daysP = 0.33Platelet GP IIb/IIIa Inhibition for Non-ST ACSPrimary Endpoint Results from the 5 Major RCTsACS治療原則2915.75.617.911.712.814.23.812.91.02.00.25All PCI trials17,3930.668.55.6All ACS trials24,3110.8912.811.4ACS

25、 troponin (+)1,3680.4216.36.9ACS PCI2,3110.6614.49.6ACS no PCI12,6850.9314.313.3ACS troponin ()2,9011.056.26.5IIb/IIIa Meta-Analysis30-Day Death, MI at 30 DaysCP944328- 1RelativeriskPlaceboIIb/IIIaNo.ratio(%)(%)Chew DP et al: JACC 2000;36:2028 35IIb/IIIa betterPlacebo betterACS治療原則301.02.00.25All PC

26、I trials17,39IIb/IIIa Inhibitors in ACS PatientsGreatest benefit 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 administration to all ACS pts

27、in whom a non-invasive strategy is plannedACS治療原則31IIb/IIIa Inhibitors in ACS PatConclusionsMuch remains to be learned about the optimal medical therapy for ACS ptsThe data favor an invasive strategy, and suggest different medications and doses ought be administered if pursuing an invasive vs. non-i

28、nvasive strategy, and in high vs. low risk ptsACS治療原則32ConclusionsMuch remains to be UA / NSTEMI: Pharmacological and Mechanical InterventionBraunwald E et al. J Am Coll Cardiol 2000;36:970-1062Braunwald E et al. Circulation 2002;106:1893-1900危險分層 (TIMI 危險評分)高危 TIMI 評分 5-7低危 TIMI 評分 0-2中危 TIMI 評分3-4

29、ASA+LMWH (普通肝素)+氯吡格雷 依替巴肽/替羅非班ASA+LMWH or 普通肝素+氯吡格雷ASA+LMWH (普通肝素)+氯吡格雷依替巴肽/替羅非班Cath/PCI/CABG進行監測 /危險評估缺血二級預防無缺血 ACS治療原則33UA / NSTEMI: Pharmacological ACS治療原則培訓課件Initiate clopidogrel (Class I, LOE: A) Consider adding IV eptifibatide or tirofiban (Class IIb, LOE: B) Conservative StrategyInitiate A/C

30、Rx (Class I, LOE: A): Acceptable options: enoxaparin or UFH (Class I, LOE: A) or fondaparinux (Class I, LOE: B), but enoxaparin or fondaparinux are preferable (Class IIA, LOE: B)Select Management StrategyASA (Class I, LOE: A)Clopidogrel if ASA intolerant (Class I, LOE: A)Diagnosis of UA/NSTEMI is Li

31、kely or DefiniteAlgorithm for Patients with UA/NSTEMI Managed by an Initial Conservative StrategyProceed with Invasive Strategy(Continued)Anderson JL. J Am Coll Cardiol. 2007. In press. Figure 8 C2 C1 AACS治療原則35Initiate clopidogrel (Class I,Evidence for Primary PCI as Treatment of Choice for STEMI A

32、CSACS治療原則36Evidence for Primary PCI as A Summary of 23 Randomized Trials (n=7739)p=0.0003p0.0001p=0.0004p0.0001OR=0.57Keeley & Grines Lancet 2003PCILyticRisk ReductionDeath28%Death/MI/CVA43%Primary PCI: The Preferred Reperfusion StrategyACS治療原則37 Summary of 23 Randomized TPrimary, Transfer, Facilita

33、ted & Rescue PCI for STEMI Primary PCI (PPCI)Direct to CVL for PCI reperfusion therapyTransfer PCIPts 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

34、mins)*Thrombolysis may be Pre-hospitalACS治療原則38Primary, Transfer, FacilitatedACS治療原則39ACS治療原則39ACS治療原則40ACS治療原則40Door-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 beneficialACS治療原則41Door-To-Balloon (DTB) Time& CEvidenc

35、e for Pre-Hospital Thrombolysis for Early ( 2 Hour) STEMIACS治療原則42Evidence for Pre-Hospital ThroEvidence to support Transfer to PCI Centers from Hospitals without PCI facilities for STEMI ACSACS治療原則43Evidence to support Transfer tEvidence Against Facilitated PCI for STEMI ACSACS治療原則44Evidence Against Facilitated PEvidence for Resue PTCA after