非ST段抬高急性冠脉综合征介入治疗

1、非ST段抬高急性冠脉综合征介入治疗-策略与选择阜外心血管病医院 乔树宾 ACS住院患者（NSTE-ACS vs STEMI）National Center for Health Statistics. 2001.ACS2.3 million hospital admissions ACS ( 230万/年 ACS住院患者）UA / NSTEMI1.43 million admissions per year（143万/年患者占63%）STEMI829,000 admissions per year（82.9万/年患者占36%）ACS主要发病机理动脉粥样硬化斑块-不稳定或破裂血栓形成炎症细胞少量

2、平滑肌细胞激活的巨噬细胞血栓ACS的病理生理基础CK- MB or TroponinTroponin elevated or notAdapted from Michael DaviesAdapted from Michael Davies ACS 无持续ST段抬高 ACS 伴持续ST段抬高ACS的临床分型ACSST 段持续抬高的 ACS无 ST 段抬高的 ACScTnT ( cTnI ) 0.1g/L或CK-MB正常上限的2倍cTnT ( cTnI ) 0.1g/L 或CK-MB正常上限的2倍STEMINSTEMI UA非ST段抬高ACS的治疗 抗血小板治疗 抗凝治疗 抗缺血治疗 调脂治疗

3、介入治疗 冠脉搭桥抗栓不溶栓抗血小板、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危险分层临床因素年龄原有基础的左室功能冠脉解剖糖尿病及肾肺功能异常等其它合并病心绞痛的病史特点 心电图或动态心电图 心肌缺血的表现 ST段和T波改变 肌钙蛋白 反应蛋白 纤维蛋白肽 BNP或NTproBNPNSTE-ACS危险分层方法 -早期CAG的价值早期冠脉造影目的： 病变范围和分布、狭窄程度和部位、适合何种血管重建术等。早期冠脉造影 - 提

4、高预后分层的可靠性 - 确定治疗方案的有效方法： 没有病变可迅速出院 罪犯病变适合 PCI 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 CABG -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.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

5、疗：计分属低危险（TIMI，GRACE）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I 2.动态ST或T改变（有症状或无症状）3.糖尿病 4.肾功能异常（GFR60ml/min/1.73m2）5.左心室功能降低（LVEF40%）6.梗塞后心绞痛7.有MI病史8.6个月内行PCI ,有CABG史9.中高GRACE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

6、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 3BVANQWISHMATEFRISC 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/NST

7、EMI Meta-analysis: Death/MI at 17 mo. F/UOverall12.214.4Trials 19999.412.4Troponin +ve10.014.0Troponin ve6.77.4Any Marker +ve14.717.4Any Marker -ve7.78.5Favors InvasiveFavors Conservative0.512TrialInv(%)Cons(%)Odds RatioP value0.0010.820.400.900.0120.820.420.890.0010.690.00010.730.920.99*TIMI 3B, VA

8、NQWISH and MATE FRISC II, TACTICS, VINO, RITA 3Data by troponin status available only in FRISC II, TACTICS, RITA 3Invasive Management of UA/NSTEMI Meta-analysis: SubgroupsMehta SR et al. JAMA 2005;293:2908-17Death or MI at Followup36018090300Probability of Death.04.03.02.010Non-Invasive (n = 1235)In

9、vasive (n = 1222)InvasiveNoninvasive RR (95 % CI) 2.2 %4.0 % 0.56 (0.35 - 0.89) p = 0.018Wallentin, Lancet 2000FRISC-II Mortality at One-Year Invasive Vs. Conservative Management Strategies FRISC II: 5 Year OutcomesEnd pointInvasivestrategy (%)Noninvasive strategy (%)Relative risk (95% CI)Death or M

10、I19.924.50.81 (0.690.95)All-causemortality9.710.10.95 (0.751.21)MI12.917.70.73 (0.600.89)Lagerqvist B. World Congress of Cardiology 2006; September 4, 2006, Barcelona, Spain.FRISC II: 5 Year OutcomesDeath or MI at 5 years in high-, medium-, and low-risk patientsEnd pointInvasivestrategy (%)Noninvasi

11、ve 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-riskpatients(FRISC 23)14.620.40.72 (0.551.13)Death or MI in low-riskpatients (FRISC 01)10.38.21.26 (0.662.40)Lagerqvist B. World Congress of Cardiology 2006; September 4, 2006,

12、 Barcelona, Spain.哪种治疗最好？（Invasive vs Conservative）Conservative（保守）920 PatientsInvasive（介入）7,018 PatientsTIMI IIIBVANQWISHMATEFRISC IITACTICS-TIMI 18VINORITA-3 TRUCS ISAR-COOL Adapted from Cannon CP. Cardiology. 2002;8(special edition):29-37.Conservative1,674 PatientsRoutine vs Selective InvasiveStr

13、ategies in ACSAdapted from Mehta S, et al. JAMA. 2005;293;2908-2917.Odds Ratio (95% CI)0.11.0OR - 0.8295% CI, 0.72-0.93P 60, ischemic EKG or biomarker AND suitable for revascularizationRANDOMIZE*Early InvasiveCoronary angiography as soon as possible (no later than 24 hours) followed by PCI or CABGDe

14、layed 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 risk of bleeding or not a suitable candidate for revascu

15、larizationFollow-up at 30 days and 6 monthsOutcomesPrimary Composite of Death, new MI or Stroke at 6 mo.SecondaryComposite of: Death, new MI or refractory ischemiaDeath, new MI, stroke, refractory ischemia or repeat revascularizationStrokeStudy Flow ChartTIMACS Stand AloneN=1,398TIMACSTotalN=3,031TI

16、MACS OASIS 5N=1,633+30 Day and 6 month Follow-up 3,029Lost to Follow-up: 4Recommended Medical TreatmentASA, clopidogrel GP IIb/IIIa inhibitor at discretion of attending physician (especially if pt is not on a thienopyridine)Antithrombin:OASIS 5: Either fondaparinux or enoxaparinTIMACS stand alone: U

17、FH or LMWH or fondaparinux or bivalirudin (investigator discretion)Beta blockerStatinParticipating CountriesNorth America 650South America 442Europe 1065Asia 846Australia 28TIMACS Steering CommitteeA. Avezum BrazilC. Morillo - ColumbiaJ-P. Bassand FranceL. Piegas BrazilW. Boden USAJ. Probstfield USA

18、J. Col BelgiumS. Qiao - ChinaR. Diaz ArgentinaH-J Rupprecht GermanyD. Faxon USAP. G. Steg FranceC. Granger USAJ-F. Tanguay-CanadaC. Joyner - CanadaP. Widimsky Czech RepM. Kenda SloveniaJ. Varigos AustraliaS. Mehta - CanadaS. Yusuf - CanadaT. Moccetti SwitzerlandJ. Zhu ChinaStudy OrganizationCoordina

19、ting Center: PHRI, McMaster 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. LawrenceCriteria for Crossover from Delayed Group to Early GroupR

20、efractory ischemiaNew MIHemodynamic instabilityCrossover from Early to Delayed: 11.9%Crossover from Delayed to Early: 25% Interventions and TimingEarlyN=1,593DelayedN=1,438Coronary Angiography (%)97.695.5Median time (h iqr)14 (3-21)50 (41-81)PCI (%)59.655.0Median time (h iqr)16 (3-23)52 (41-101)CABG

21、 (%)14.713.6Median time (d iqr)7.7 (4.7-17.4)10.8 (6.7-19.8)Iqr=interquartile rangeBaseline CharacteristicsEarlyN=1,593DelayedN=1,438Age65.165.8% Female34.834.7Diabetes26.527.3Prior MI19.720.9Prior PCI13.814.1Prior CABG7.07.3Prior Stroke7.27.5Ischemic ECG 80.579.9Elevated Biomarker77.276.9In-Hospita

22、l MedicationsEarlyN=1,593DelayedN=1,438ASA98.098.1Thieonopyridine87.286.7Thienopyridine or GP IIb/IIIa inhibitor88.288.4GP IIb/IIIa Inhibitor23.222.5AnticoagulantUFH24.624.6LMWH64.064.6Fondaparinux41.941.3Bivalirudin0.50.4Beta Blocker86.886.9Statin85.084.3Primary and Secondary OutcomesEarlyN=1,593De

23、layedN=1,438HR 95% CIPDeath, MI, Stroke9.711.40.850.68-1.060.15Death, MI, refractory ischemia9.613.10.720.58-0.890.002Death, MI, Stroke, refractory ischemia + repeat intervention16.719.70.840.71-0.990.039Death4.96.00.810.60-1.110.19MI4.85.80.830.61-1.140.25Stroke1.31.40.900.48-1.680.74Ref. Ischemia1

24、.03.30.300.17-0.53= 3 g/dL2.32.6Transfusion 2 U2.22.9Pre-specified SubgroupsOverallAge =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 -

25、1.06 )0.98 ( 0.64 - 1.52 )0.83 ( 0.64 - 1.07 )0.77 ( 0.54 - 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-Value0.330.50.71.001.52.03.0Early better Delayed bette

26、r Hazard Ratio (95% CI)Early%11.4 6.514.812.310.98.714.310.511.76.721.6Delayed% GRACE Risk Score: Primary OutcomeHR 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.ConclusionsOverall, we found no significant d

27、ifference between an early and a delayed 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 invasiv

28、e strategy also had a large impact on reducing the rate of refractory ischemia by 70%.There were no significant differences in major bleeding or other safety concerns between the two strategiesImplicationsMost patients with ACS can be managed safely with either an early or a delayed invasive strateg

29、yIn a subset of patients at highest risk (GRACE 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 economi

30、c considerations.TIMACSAn International Randomized 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 Patie

31、nts with Non-ST Segment Elevation Acute Coronary 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 C

32、oronary Syndromes180天随访主要终点事件（死亡、心梗、卒中） 早期介入组 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 Ele

33、vation Acute Coronary Syndromes180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 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

34、.05TIMACSAn International Randomized Trial of 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

35、 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、难治性心肌缺血、再次血运重建 早期介入组 23.5% 延迟介入组 26.6% （P=0.32）TIMACSAn Internationa

36、l Randomized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes*P0.05TIMACSAn International Randomized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes180天随访安全性终点-大出血

37、 早期介入组 0.7% 延迟介入组 0.5% （P=1.00） 30天随访安全性终点-大出血 早期介入组 0.7% 延迟介入组 0.3% （P=0.75） ESC 指南（一）对于伴有ST段动态改变顽固性或反复发作的心绞痛，心衰，恶性心律失常或血流动力学不稳定者应做紧急冠状动脉造影（I-C）对于具有中高危险特征的患者应做早期冠状动脉造影（72小时），进行血运重建（PCI或CABG）（I-A）不推荐常规对没有中高危险特征的患者进行有创评价（III-C），建议进行能够诱发心肌缺血的无创检查（I-C）ESC血运重建指南（二）不推荐对非显著病变进行PCI（III-C）选择BMS或DES时，应仔细认真评估

38、风险-效益比，合并病和是否近期非心脏手术停用双重抗血小板药物的可能性（I-C）ESC血运重建（三）造影没有显著病变药物治疗造影有显著病变：单支病变处理罪犯病变；多支：PCI或CABG的选择应个体化 有些仅处理罪犯病变以后再择期外科提倡介入术前应用GPIIb/IIIa拮抗剂如计划搭桥，波立维应停用5天NSTE-ACS不完全或完全”罪犯”血管再血管化治疗?Anibal A Damonte,Argenitina.Am J Cardiol.2007,TCT出院及出院后的治疗特别强调各种危险因素的控制生活方式的改善规律服药NSTEACS介入治疗选择NSTEACS患者的自然转归差别很大，危险分层有助于判断

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46、Zr$u(x+B2E5H9KcNfRiUlXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E6H9KcOfRiUmXp!s&v)z0C3F7IaMdPgSkVnYq$t*w-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v(y+B3E6I9LcOgRjUmYp!s&w)z1C4F7JaMdPhSkWnZq$u*x-A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LdOgRjVmYp!t&w-z1C4

47、G7JaMePhTkWnZr$u*x+A2D5H8KcNfQiUlXo#s%v)y0B3F6I9LdOdOgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H9KcNfRiUlXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%v(y+B3E6H9LcOgR

48、jUmYp!s&w)z1C4F7JaMdPhSkWnZq$u*x-A2D5H8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZr$u*x+A2D5H8KcNfQiUlXo#s%v)y0B3F6I9LdOgSgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVnYq!t*w-z1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u

49、(y+B2E6H9KcOfRjUmXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmYp!s&w)z0C4F7JaMdPhSkVnZq$u*x-A2D5G8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnWnZr$u*x+A2D5H8KbNfQiUlXo#s%v(y0B3F6I9LdOgRjVmYq!t&w-z1C4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVmYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u(y+B2E6H9KcOfRiUmXp!s&v)z0C3F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQiTlWo#r%u(