ACS治疗原则培训课件

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

2、CS治疗原则3ST Segment Depression (Non-traACS治疗原则4ACS治疗原则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治疗原则5NSTE ACS : Key ThemesNSTE ACS:Antman EM et al N Engl J Med 1996;335:1342-9ACS治疗原则6ACS治疗原则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治疗原则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治疗原则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治疗原则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治疗原则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治疗原则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治疗原则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治疗原则

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治疗原则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治疗原则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治疗原则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治疗原则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治疗原则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治疗原则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治疗原则20Trial: .751.01.5(P=0CLASS Ia （Ia 级推荐）一旦出现UA/NSTEMI，需尽快在抗血小板治疗的基础上给予患者抗凝药物。a. 介入方案：证据级别A-包括依诺肝素和普通肝素；证据级别B-包括比伐卢定和戊聚糖钠b. 保守方案：药物选择可以是依诺肝素、普通肝素（证据级别A）或者戊聚糖钠（证据级别B），有效性已经确立。c.对于选择保守治疗的病人，如果有较高的出血风险，倾向于选择

19、戊聚糖钠（证据级别B）CLASS IIa （IIa 级推荐）对于最初选择保守治疗策略的UA/NSTEMI病人，作为抗凝治疗，依诺肝素或者戊聚糖钠要优于普通肝素，除非计划在24小时内进行冠脉搭桥手术。（证据级别B）2007年ACC/AHA UA/NSTEMI的指南抗凝治疗推荐ACS治疗原则21CLASS Ia （Ia 级推荐）2007年ACC/AHA ACC/AHA 2007更新的抗凝治疗指南高危或确诊ACS实行导管或PCI 疑似/确诊ACS 可能ACS阿司匹林+IV UFH/LMWH*GP IIb/IIIa拮抗剂阿司匹林+皮下 LMWH *或 IV UFH氯吡格雷氯吡格雷阿司匹林*证据等级Ia

20、：依诺肝素优于IV UFHACS治疗原则22ACC/AHA 2007更新的抗凝治疗指南高危或确诊ACS实ACC/AHA 治疗建议2007 “不稳定型心绞痛/非ST段抬高心梗患者，除非计划在24小时内行冠脉搭桥手术，相对于普通肝素，依诺肝素（Enoxaparin）作为抗凝剂应优先选用。(证据级别 A )”2002 update ACC/AHA guidelineACS治疗原则23ACC/AHA 治疗建议2007 “不稳定型心绞痛/非SACCP7指南对LMWH的治疗建议急性期LMWH优于UFH（1B级）；LMWH治疗时不需常规监测（1C级）；已使用LMWH的患者如需进行PCI，应继续使用LMWH（

21、2C级）；应用GPIIb/IIIa 受体拮抗剂者，LMWH安全性优于UFH（2B级）。NSTE ACS 患者中LMWH的疗程评价是：NSTE ACS患者应早期介入治疗，如果冠脉干预延迟，可考虑延长LMWH治疗作为血运重建的“桥梁”。 ACS治疗原则24ACCP7指南对LMWH的治疗建议急性期LMWH优于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治疗原则25Rest pain 5 min andHeparinBiTIMI - 8: Bivalirudin vs. Placebo in ACS4-6 wks7 days4-6 wks7 daysp=0.008p=0.024p=NSp=NSACS治疗原则26TIMI - 8: Bivalirudin vs. PlacACS治疗原则27ACS治疗原则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治疗原则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治疗原则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治疗原则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治疗原则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治疗原则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危险分层 (TIMI 危险评分)高危 TIMI 评分 5-7低危 TIMI 评分 0-2中危 TIMI 评分3-4

29、ASA+LMWH (普通肝素)+氯吡格雷 依替巴肽/替罗非班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/替罗非班Cath/PCI/CABG进行监测 /危险评估缺血二级预防无缺血 ACS治疗原则33UA / NSTEMI: Pharmacological ACS治疗原则培训课件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治疗原则35Initiate clopidogrel (Class I,Evidence for Primary PCI as Treatment of Choice for STEMI A

32、CSACS治疗原则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治疗原则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治疗原则38Primary, Transfer, FacilitatedACS治疗原则39ACS治疗原则39ACS治疗原则40ACS治疗原则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治疗原则41Door-To-Balloon (DTB) Time& CEvidenc

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