非ST段抬高急性冠脉综合征介入治疗

1、非非STST段抬高急性冠脉综合征介入治疗段抬高急性冠脉综合征介入治疗- -策略与选择策略与选择阜外心血管病医院阜外心血管病医院 乔树宾乔树宾 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 ( 230万万/年年 ACS住院患者）住院患者）1.43 million admissions per year（143万万/年患者占年患者占63%）829,000 admissions per year（82.9万万/年患者占年患

2、者占36%）ACS主要发病机理主要发病机理 动脉粥样硬化斑块动脉粥样硬化斑块-不稳定或破裂不稳定或破裂 血栓形成血栓形成血栓血栓ACS的病理生理基础的病理生理基础CK- MB or TroponinTroponin elevated or notAdapted from Michael DaviesAdapted from Michael Davies ACS 无持续无持续ST段抬高段抬高 ACS 伴持续伴持续ST段抬高段抬高ACS的临床分型的临床分型ACSST 段持续抬高的段持续抬高的 ACS无无 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的治疗的治疗 抗血小板治疗 抗凝治疗 抗缺血治疗 调脂治疗 介入治疗 冠脉搭桥抗栓抗栓不溶栓不溶栓抗血小板、抗凝抗血小板、抗凝PCI ？！？！诊 断 常规血生化，特别包括Tn T或I 监测心电ST段的变化 超声心动图检查 如需排除主动脉夹层，做MRI； 排除肺栓塞行CT或核素检查 观察对抗缺血治疗的效果 评定危险记分 评价出血的危险性NSTE-ACS危险分层危险分层 临床因素临床因素 年龄年龄 原有基础的左室功能原有基础的左室功能 冠脉解剖冠脉

4、解剖 糖尿病及肾肺功能异糖尿病及肾肺功能异常等其它合并病常等其它合并病 心绞痛的病史特点心绞痛的病史特点 心电图或动态心电图心电图或动态心电图 心肌缺血的表现心肌缺血的表现 STST段和段和T T波改变波改变 肌钙蛋白肌钙蛋白 反应蛋白反应蛋白 纤维蛋白肽纤维蛋白肽 BNP 或或NTproBNP NSTE-ACSNSTE-ACS危险分层方法危险分层方法 - -早期早期CAGCAG的价值的价值 早期冠脉造影目的：早期冠脉造影目的： 病变范围和分布、狭窄程度和部位、适合何种血管重建术等。病变范围和分布、狭窄程度和部位、适合何种血管重建术等。 早期冠脉造影早期冠脉造影 - 提高预后分层的可靠性提高预

5、后分层的可靠性 - 确定治疗方案的有效方法：确定治疗方案的有效方法： 没有病变可迅速出院没有病变可迅速出院 罪犯病变适合罪犯病变适合 PCI PCI 者可立即介入治疗加快出院者可立即介入治疗加快出院 左主干病变、复杂病变伴左室功能不全者迅速左主干病变、复杂病变伴左室功能不全者迅速 CABGCABG -发现高危病人，使患者从早期血管重建术中获益发现高危病人，使患者从早期血管重建术中获益ACC/AHA：治疗的选择（一） 有创治疗：1.尽管充分药物治疗仍发生静息或低水平活动心绞痛；2.TnT或TnI升高；3.新出现的ST压低；4.HF体征和症状或新出现或加重的二尖瓣返流；5.无创检查有高危的证据；6

6、.持续性室速；7.六个月内曾PCI；8.先前CABG；9.危险积分属高危（TIMI，GRACE）；10.左心室功能降低（LVEF40%）ACC/AHA：治疗的选择（二） 保守治疗：保守治疗：计分属低危险（计分属低危险（TIMI，GRACE）无高危特征的患者或医生选择无高危特征的患者或医生选择2007-ESC介入治疗紧急（Urgent）1.患者出现持续性或反复胸痛，伴有或不伴有ST改变（2mm）或深的倒置T波，抗缺血治疗效果不好2.出现心衰临床症状或血流动力学不稳定3.致命性心律失常（VF、VT）早期72小时1.Tn T或或I 2.动态动态ST或或T改变（有症状或无症状）改变（有症状或无症状）3

7、.糖尿病糖尿病 4.肾功能异常（肾功能异常（GFR60ml/min/1.73m2）5.左心室功能降低（左心室功能降低（LVEF40%）6.梗塞后心绞痛梗塞后心绞痛7.有有MI病史病史8.6个月内行个月内行PCI ,有有CABG史史9.中高中高GRACE危险记分危险记分不做或择期做 无再发胸痛 无心衰的体征 无新的ECG改变（就诊6-12小时） TnT 或I正常（就诊6-12小时）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)哪种治疗最好？哪种治疗最好？（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 对比非ST段抬高的急性冠状动脉综合征患者早期与延迟干预治疗的国际随机研究中国亚组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名患者入选本研究 早期介入组 446名，随访率98.4% 延迟介入组 369名，随访率98.8% 临床基线、合并用药及冠造结果两组无统计学差异 冠造的平均时间 早期介入组18.4小时 延迟介入组72.6小时 TIMACSAn International Randomized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes180天随访主要终点事件（死亡、心梗、卒中） 早期介入组

33、9.0% 延迟介入组 14.6% （P=0.01） - 死亡 早期介入组 3.6% 延迟介入组 3.3% （P=0.79） - 心梗 早期介入组 5.2% 延迟介入组 10.8% （P=0.002） - 卒中 早期介入组 0.2% 延迟介入组 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天随访次要终点事件 死亡

34、、心梗、难治性心肌缺血 早期介入组 14.6% 延迟介入组 22.0% （P=0.01） 死亡、心梗、卒中、难治性心肌缺血、再次血运重建 早期介入组 26.7% 延迟介入组 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天随访主要终点事件（死亡、心梗、卒中） 早期介入组 8.1% 延迟介入组 12.5% （P=0.04） - - 死亡 早期介入组 2.9% 延迟介入组 2.2% （P=0.503） - 心梗 早期介入组 5.2% 延迟介入组 10.0% （P=0.01） - 卒中 早期介入组 0% 延迟介入组 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天随访次要终点事件 死亡、心梗、难治性心肌缺血 早期介入组 13.0% 延迟介入组 19.0% （P=0.02） 死亡、心梗、卒中、