非ST段抬高急性冠脈綜合征介入治療

1、非非STST段抬高急性冠脈綜合征介入治療段抬高急性冠脈綜合征介入治療- -策略與選擇策略與選擇阜外心血管病醫(yī)院阜外心血管病醫(yī)院 喬樹賓喬樹賓 ACS住院患者住院患者（NSTE-ACS vs STEMI）National Center for Health Statistics. 2001.ACS2.3 million hospital admissions ACS ( 230萬萬/年年 ACS住院患者）住院患者）1.43 million admissions per year（143萬萬/年患者占年患者占63%）829,000 admissions per year（82.9萬萬/年患者占年患

2、者占36%）ACS主要發(fā)病機理主要發(fā)病機理 動脈粥樣硬化斑塊動脈粥樣硬化斑塊-不穩(wěn)定或破裂不穩(wěn)定或破裂 血栓形成血栓形成血栓血栓ACS的病理生理基礎(chǔ)的病理生理基礎(chǔ)CK- MB or TroponinTroponin elevated or notAdapted from Michael DaviesAdapted from Michael Davies ACS 無持續(xù)無持續(xù)ST段抬高段抬高 ACS 伴持續(xù)伴持續(xù)ST段抬高段抬高ACS的臨床分型的臨床分型ACSST 段持續(xù)抬高的段持續(xù)抬高的 ACS無無 ST 段抬高的段抬高的 ACScTnT ( cTnI ) 0.1g/L或或CK-MB正常上限的

3、正常上限的2倍倍cTnT ( cTnI ) 0.1g/L 或或CK-MB正常上限的正常上限的2倍倍STEMINSTEMI UA非非ST段抬高段抬高ACS的治療的治療 抗血小板治療 抗凝治療 抗缺血治療 調(diào)脂治療 介入治療 冠脈搭橋抗栓抗栓不溶栓不溶栓抗血小板、抗凝抗血小板、抗凝PCI ？??？！診 斷 常規(guī)血生化，特別包括Tn T或I 監(jiān)測心電ST段的變化 超聲心動圖檢查 如需排除主動脈夾層，做MRI； 排除肺栓塞行CT或核素檢查 觀察對抗缺血治療的效果 評定危險記分 評價出血的危險性NSTE-ACS危險分層危險分層 臨床因素臨床因素 年齡年齡 原有基礎(chǔ)的左室功能原有基礎(chǔ)的左室功能 冠脈解剖冠脈

4、解剖 糖尿病及腎肺功能異糖尿病及腎肺功能異常等其它合并病常等其它合并病 心絞痛的病史特點心絞痛的病史特點 心電圖或動態(tài)心電圖心電圖或動態(tài)心電圖 心肌缺血的表現(xiàn)心肌缺血的表現(xiàn) STST段和段和T T波改變波改變 肌鈣蛋白肌鈣蛋白 反應(yīng)蛋白反應(yīng)蛋白 纖維蛋白肽纖維蛋白肽 BNP 或或NTproBNP NSTE-ACSNSTE-ACS危險分層方法危險分層方法 - -早期早期CAGCAG的價值的價值 早期冠脈造影目的：早期冠脈造影目的： 病變范圍和分布、狹窄程度和部位、適合何種血管重建術(shù)等。病變范圍和分布、狹窄程度和部位、適合何種血管重建術(shù)等。 早期冠脈造影早期冠脈造影 - 提高預(yù)后分層的可靠性提高預(yù)

5、后分層的可靠性 - 確定治療方案的有效方法：確定治療方案的有效方法： 沒有病變可迅速出院沒有病變可迅速出院 罪犯病變適合罪犯病變適合 PCI PCI 者可立即介入治療加快出院者可立即介入治療加快出院 左主干病變、復(fù)雜病變伴左室功能不全者迅速左主干病變、復(fù)雜病變伴左室功能不全者迅速 CABGCABG -發(fā)現(xiàn)高危病人，使患者從早期血管重建術(shù)中獲益發(fā)現(xiàn)高危病人，使患者從早期血管重建術(shù)中獲益ACC/AHA：治療的選擇（一） 有創(chuàng)治療：1.盡管充分藥物治療仍發(fā)生靜息或低水平活動心絞痛；2.TnT或TnI升高；3.新出現(xiàn)的ST壓低；4.HF體征和癥狀或新出現(xiàn)或加重的二尖瓣返流；5.無創(chuàng)檢查有高危的證據(jù)；6

6、.持續(xù)性室速；7.六個月內(nèi)曾PCI；8.先前CABG；9.危險積分屬高危（TIMI，GRACE）；10.左心室功能降低（LVEF40%）ACC/AHA：治療的選擇（二） 保守治療：保守治療：計分屬低危險（計分屬低危險（TIMI，GRACE）無高危特征的患者或醫(yī)生選擇無高危特征的患者或醫(yī)生選擇2007-ESC介入治療緊急（Urgent）1.患者出現(xiàn)持續(xù)性或反復(fù)胸痛，伴有或不伴有ST改變（2mm）或深的倒置T波，抗缺血治療效果不好2.出現(xiàn)心衰臨床癥狀或血流動力學(xué)不穩(wěn)定3.致命性心律失常（VF、VT）早期72小時1.Tn T或或I 2.動態(tài)動態(tài)ST或或T改變（有癥狀或無癥狀）改變（有癥狀或無癥狀）3

7、.糖尿病糖尿病 4.腎功能異常（腎功能異常（GFR60ml/min/1.73m2）5.左心室功能降低（左心室功能降低（LVEF40%）6.梗塞后心絞痛梗塞后心絞痛7.有有MI病史病史8.6個月內(nèi)行個月內(nèi)行PCI ,有有CABG史史9.中高中高GRACE危險記分危險記分不做或擇期做 無再發(fā)胸痛 無心衰的體征 無新的ECG改變（就診6-12小時） TnT 或I正常（就診6-12小時）0.20.5125Favors InvasiveFavors ConservativeOdds Ratio Death or MIOR 0.82, P=0.001TrialTIMI 3BVANQWISHMATEFRIS

8、C IITACTICSRITA 3TOTALMehta SR et al. JAMA 2005;293:2908-175.1%8.1%27.2%28.0%12.0%8.9%4.3%11.4%4.0%5.3%7.4%10.9%VINO4.8%14.8%InvCons7.4%11.0%Invasive Management of UA/NSTEMI Meta-analysis: Death/MI at 17 mo. F/UOverall12.214.4Trials 19999.412.4Troponin +ve10.014.0Troponin ve6.77.4Any Marker +ve14.71

9、7.4Any Marker -ve7.78.5Favors Invasive Favors Conservative0.512TrialInv(%)Cons(%)Odds Ratio P value0.0010.820.400.900.0120.820.420.890.0010.690.00010.730.920.99*TIMI 3B, VANQWISH and MATE FRISC II, TACTICS, VINO, RITA 3Data by troponin status available only in FRISC II, TACTICS, RITA 3Invasive Manag

10、ement of UA/NSTEMI Meta-analysis: SubgroupsMehta SR et al. JAMA 2005;293:2908-17Death or MI at Followup36018090300.04.03.02.010FRISC-II Mortality at One-Year Invasive Vs. Conservative Management Strategies FRISC II: 5 Year OutcomesEnd pointInvasivestrategy (%)Noninvasive strategy (%)Relative risk (9

11、5% CI)Death or MI19.924.50.81 (0.690.95)All-causemortality9.710.10.95 (0.751.21)MI12.917.70.73 (0.600.89)FRISC II: 5 Year OutcomesEnd pointInvasivestrategy (%)Noninvasive strategy (%)Relative risk (95% CI)Death or MI in high-risk patients(FRISC 47)32.741.60.79 (0.640.97)Death or MI inmedium-riskpati

12、ents(FRISC 23)14.620.40.72 (0.551.13)Death or MI in low-riskpatients (FRISC 01)10.38.21.26 (0.662.40)哪種治療最好？哪種治療最好？（Invasive vs Conservative）Conservative（保守）保守）920 PatientsInvasive（介入）介入）7,018 PatientsTIMI IIIBVANQWISHMATEFRISC IITACTICS-TIMI 18VINORITA-3 TRUCS ISAR-COOL Adapted from Cannon CP. Card

13、iology. 2002;8(special edition):29-37.Conservative1,674 PatientsRoutine vs Selective InvasiveStrategies in ACSOdds Ratio (95% CI)0.11.0Composite of Death or Myocardial InfarctionNo./Total (%)FavorsRoutineInvasiveFavorsSelectiveInvasive10StudyMortality during hospitalizationMortality after dischargeC

14、ons (%)Inv (%)Odds Ratio, 95% CITIMI 3B3.32.80.1 0.20.512510Favors RoutineFavors SelectiveVANQWISH11.713.4MATE6.910.0FRISC II3.01.2TACTICS2.81.9VINO9.41.6RITA 37.35.2Subtotal1.11.8TIMI 3B1.92.2VANQWISH1.34.5MATE3.30.9FRISC II0.91.1TACTICS0.71.4VINO4.51.6RITA 30.71.6Subtotal3.84.9Mehta SR et al. JAMA

15、 2005;293:2908-17OR 1.60, P=0.007OR 0.76, P=0.01Invasive Rx in ACS: Early and Late MortalityCRUSADE: Invasive Cardiac Procedures in the USProcedures Performed (non-transfer)Diagnostic Cath 64 % Within 48 hours41 % Within 24 hours27 %Percutaneous Intervention 35 % Within 48 hours25 %Coronary Bypass G

16、rafting 11 %An International Randomized Trial ofEarly Versus Delayed Invasive Strategiesin Patients with Non-ST Segment Elevation Acute Coronary SyndromesFUNDED BY THE CANADIAN INSTITUTES OF HEALTH RESEARCHGrant # 150904TIMACS Timing of Intervention in patients with Acute Coronary Syndromes To deter

17、mine whether early intervention is superior to delayed intervention in patients with high risk non-ST segment elevation acute coronary syndromeUA or NSTEMI2 of 3 Criteria: Age 60, ischemic EKG or biomarker AND suitable for revascularizationRANDOMIZE*Early InvasiveCoronary angiography as soon as poss

18、ible (no later than 24 hours) followed by PCI or CABGDelayed InvasiveCoronary angiography any time 36 hrs followed by PCI or CABGASA, clopidogrel, GP IIb/IIIa antagonist as per routine practice*Center chose randomization ratio 1:1, 1:2 or 2:1 Early: DelayedExcludedContraindication for LMWH or high r

19、isk of bleeding or not a suitable candidate for revascularizationFollow-up at 30 days and 6 monthsTIMACS Stand AloneN=1,398TIMACSTotalN=3,031TIMACS OASIS 5N=1,633+30 Day and 6 month Follow-up 3,029Lost to Follow-up: 4ASA, clopidogrel GP IIb/IIIa inhibitor at discretion of attending physician (especi

20、ally if pt is not on a thienopyridine)Antithrombin:OASIS 5: Either fondaparinux or enoxaparinTIMACS stand alone: UFH or LMWH or fondaparinux or bivalirudin (investigator discretion)Beta blockerStatinNorth America 650South America 442Europe 1065Asia 846Australia 28Coordinating Center: PHRI, McMaster

21、University S. Mehta, S. Yusuf, S. Jolly, C. Horsman, S. Chrolavicius, B. MeeksDSMB: P. Sleight (chair), J. Anderson, D. DeMets, D. Johnstone, D. HolmesAdjudication Committee Chair: C. Joyner Coordinator: M. LawrenceIqr=interquartile rangeDeath, MI, StrokeDeath, MI, refractory ischemiaDeath, MI, Stro

22、ke, refractory ischemia + repeat interventionDeathMIStrokeRef. IschemiaRep. Intervention*At 30 days: 5.9 vs 4.2%, HR 1.39, 95% CI 1.00-1.95, P=0.047DaysCumulative Hazard0.0 0.020.060.100306090120150180Death/MI/Stroke at 180 daysEarlyNo. at RiskDelayedEarly14381328126912541234122912111593148414131398

23、139113821363DelayedHR 0.8595% CI 0.68-1.06P= 0.15 DaysCumulative Hazard0.00.040.080.120306090120150180Death/MI/RI at 180 daysDelayedEarlyNo. at RiskDelayedEarly14381303124312301209120511871593148514171402139413861366HR 0.7295% CI 0.58-0.79P=0.002 Death/MI/RI/Stroke/Rep Int at 180 daysDaysCumulative

24、Hazard0.00.050.100.150.200306090120150180DelayedEarlyNo. at RiskDelayedEarly14381250116611501128111810971593140013211304128712761256HR 0.8495% CI 0.71-0.99P=0.039 Major Bleed during initial hospitalization3.13.50.880.60-1.310.53ICH00.1Surg Intervention0.40.8Retroperitoneal0.10.2 Hb = 3 g/dL2.32.6Tra

25、nsfusion 2 U2.22.9OverallAge =65FemaleMaleNo ST deviationST deviationNo elevated markerElevated MarkerGRACE 0-140GRACE =1413031129317361052197615231508668236320709619.76.512.39.79.87.611.710.59.57.714.10.4630.5400.7220.4230.00970.85 ( 0.68 - 1.06 )0.98 ( 0.64 - 1.52 )0.83 ( 0.64 - 1.07 )0.77 ( 0.54

26、- 1.12 )0.89 ( 0.68 - 1.18 )0.88 ( 0.62 - 1.26 )0.81 ( 0.61 - 1.07 )1.00 ( 0.62 - 1.60 )0.81 ( 0.63 - 1.04 )1.14 ( 0.82 - 1.58 )0.65 ( 0.48 - 0.88 )NCharacteristicHR (95% CI)Interaction p-Value0.33 0.5 0.7 1.00 1.52.0 3.0Early better Delayed better Hazard Ratio (95% CI)Early%11.4 6.514.812.310.98.71

27、4.310.511.76.721.6Delayed%6.721.67.714.10510152025Death/MI/Stroke at 6 mo. (%)DelayedEarlyHR 1.1495% CI 0.82-1.58P=0.43 HR 0.6595% CI 0.48-0.88P=0.005Interaction P=0.0097Low/Int RiskGRACE Score = 140N=961Death, MI or Stroke at 6 mo.Overall, we found no significant difference between an early and a d

28、elayed invasive strategy for prevention of death, MI or stroke (primary outcome).However, in the subgroup at highest risk (GRACE score 140), an early invasive strategy was superior to a delayed invasive strategy for prevention of death, MI or strokeThe early invasive strategy also had a large impact

29、 on reducing the rate of refractory ischemia by 70%.There were no significant differences in major bleeding or other safety concerns between the two strategiesMost patients with ACS can be managed safely with either an early or a delayed invasive strategyIn a subset of patients at highest risk (GRAC

30、E score140), early intervention is superior and these patients should be taken to the cath lab as early as possibleIn all other patients, the decision regarding timing of intervention can depend on other factors, such as cath lab availability and economic considerations.TIMACSAn International Random

31、ized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes 對比非ST段抬高的急性冠狀動脈綜合征患者早期與延遲干預(yù)治療的國際隨機研究中國亞組TIMACSAn International Randomized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Corona

32、ry Syndromes共有815名患者入選本研究 早期介入組 446名，隨訪率98.4% 延遲介入組 369名，隨訪率98.8% 臨床基線、合并用藥及冠造結(jié)果兩組無統(tǒng)計學(xué)差異 冠造的平均時間 早期介入組18.4小時 延遲介入組72.6小時 TIMACSAn International Randomized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes180天隨訪主要終點事件（死亡、心梗、卒中） 早期介入組

33、9.0% 延遲介入組 14.6% （P=0.01） - 死亡 早期介入組 3.6% 延遲介入組 3.3% （P=0.79） - 心梗 早期介入組 5.2% 延遲介入組 10.8% （P=0.002） - 卒中 早期介入組 0.2% 延遲介入組 0.5% （P=0.87）TIMACSAn International Randomized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes180天隨訪次要終點事件 死亡

34、、心梗、難治性心肌缺血 早期介入組 14.6% 延遲介入組 22.0% （P=0.01） 死亡、心梗、卒中、難治性心肌缺血、再次血運重建 早期介入組 26.7% 延遲介入組 30.4% （P=0.25）TIMACSAn International Randomized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes*P0.05TIMACSAn International Randomized Trial of

35、Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes30天隨訪主要終點事件（死亡、心梗、卒中） 早期介入組 8.1% 延遲介入組 12.5% （P=0.04） - - 死亡 早期介入組 2.9% 延遲介入組 2.2% （P=0.503） - 心梗 早期介入組 5.2% 延遲介入組 10.0% （P=0.01） - 卒中 早期介入組 0% 延遲介入組 0.3% （P=0.45）TIMACSAn International Randomized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes30天隨訪次要終點事件 死亡、心梗、難治性心肌缺血 早期介入組 13.0% 延遲介入組 19.0% （P=0.02） 死亡、心梗、卒中、