非st段抬高急性冠脉综合征介入治疗课件

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. ACS 2.3 million hospital admissions ACS ( 230万/年 ACS住院患者） UA / NSTEMIUA / NSTEMI 1.43 million admissions per year （143万/年患者占63%） STEMISTEMI 829,000 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 炎症炎症 细胞细胞 少量少量平滑肌平滑肌 细胞细胞 激活激活的巨噬细胞的巨噬细胞 血栓 ACS的病理生理基础 CK- MB or Troponin Troponin elevated or not Adapted from Michael Davies Adapted 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 ACS ST 段持续抬高的 ACS无 ST 段抬高的 ACS cTnT ( cTnI ) 0.1g/L 或CK-MB正常上限的2倍 cTnT ( cTnI ) 0.1g/L 或CK-MB 19999.412.4 Troponin +ve10.014.0 Troponin ve6.77.4 Any Marker +ve14.717.4 Any Marker -ve7.78.5 Favors Invasive Favors Conservative 0.512 TrialInv (%) Cons (%) Odds Ratio P value 0.0010.82 0.400.90 0.0120.82 0.420.89 0.0010.69 0.00010.73 0.920.99 *TIMI 3B, VANQWISH and MATE FRISC II, TACTICS, VINO, RITA 3 Data by troponin status available only in FRISC II, TACTICS, RITA 3 Invasive Management of UA/NSTEMI Meta-analysis: Subgroups Mehta SR et al. JAMA 2005;293:2908-17 Death or MI at Followup 36018090300 Probability of Probability of D Deatheath .04 .03 .02 .01 0 Non-Invasive (n = 1235)Non-Invasive (n = 1235) Invasive (n = 1222)Invasive (n = 1222) InvasiveInvasiveNoninvasive Noninvasive RR (95 % CI) RR (95 % CI) 2.2 %2.2 %4.0 %4.0 % 0.56 (0.35 - 0.89) p = 0.018 0.56 (0.35 - 0.89) p = 0.018 WallentinWallentin, Lancet 2000, Lancet 2000 FRISC-II Mortality at One-Year Invasive Vs. Conservative Management Strategies FRISC II: 5 Year Outcomes End point Invasive strategy (%) Noninvasive strategy (%) Relative risk (95% CI) Death or MI 19.924.5 0.81 (0.690.95) All-cause mortality 9.710.1 0.95 (0.751.21) MI12.917.7 0.73 (0.600.89) LagerqvistLagerqvist B. World Congress of Cardiology 2006; September 4, 2006, Barcelona, Spain. B. World Congress of Cardiology 2006; September 4, 2006, Barcelona, Spain. FRISC II: 5 Year Outcomes Death or MI at 5 years in high-, medium-, and low-risk patientsDeath or MI at 5 years in high-, medium-, and low-risk patients End point Invasive strategy (%) Noninvasive strategy (%) Relative risk (95% CI) Death or MI in high-risk patients (FRISC 47) 32.741.6 0.79 (0.640.97) Death or MI in medium-risk patients (FRISC 23) 14.620.4 0.72 (0.55 1.13) Death or MI in low-risk patients (FRISC 01) 10.38.2 1.26 (0.66 2.40) LagerqvistLagerqvist B. World Congress of Cardiology 2006; September 4, 2006, Barcelona, Spain. B. World Congress of Cardiology 2006; September 4, 2006, Barcelona, Spain. 哪种治疗最好？ （Invasive vs Conservative） Conservative（保守） 920 Patients Invasive（介入） 7,018 Patients TIMI IIIB VANQWISH MATE FRISC II TACTICS- TIMI 18 VINO RITA-3 TRUCS ISAR-COOL Adapted from Cannon CP. Cardiology. 2002;8(special edition):29-37. Conservative 1,674 Patients Routine vs Selective Invasive Strategies in ACS Adapted from Adapted from MehtaMehta S, et al. S, et al. JAMA. JAMA. 2005;293;2908-2917.2005;293;2908-2917. Odds Ratio (95% CI) 0.11.0 OR - 0.82OR - 0.82 95% CI, 0.72-0.9395% CI, 0.72-0.93 P 60, ischemic EKG or biomarker AND suitable for revascularization RANDOMIZE* Early Invasive Coronary angiography as soon as possible (no later than 24 hours) followed by PCI or CABG Delayed Invasive Coronary angiography any time 36 hrs followed by PCI or CABG ASA, clopidogrel, GP IIb/IIIa antagonist as per routine practice *Center chose randomization ratio 1:1, 1:2 or 2:1 Early: Delayed Excluded Contraindication for LMWH or high risk of bleeding or not a suitable candidate for revascularization Follow-up at 30 days and 6 months TIMACSTIMACS OutcomesOutcomes Primary Primary Composite of Death, new MI or Stroke at 6 mo.Composite of Death, new MI or Stroke at 6 mo. SecondarySecondary Composite of: Composite of: 1.1.Death, new MI or refractoryDeath, new MI or refractory ischemia ischemia 2.2.Death, new MI, stroke, refractoryDeath, new MI, stroke, refractory ischemia ischemia or repeator repeat revascularization revascularization 3.3.StrokeStroke TIMACSTIMACS Study Flow ChartStudy Flow Chart TIMACS Stand Alone N=1,398 TIMACS Total N=3,031 TIMACS OASIS 5 N=1,633 + 30 Day and 6 month Follow-up 3,029 Lost to Follow-up: 4 TIMACSTIMACS Recommended Medical TreatmentRecommended Medical Treatment ASA, clopidogrel GP IIb/IIIa inhibitor at discretion of attending physician (especially if pt is not on a thienopyridine) Antithrombin: OASIS 5: Either fondaparinux or enoxaparin TIMACS stand alone: UFH or LMWH or fondaparinux or bivalirudin (investigator discretion) Beta blocker Statin TIMACSTIMACS Participating CountriesParticipating Countries North America 650 South America 442 Europe 1065 Asia 846 Australia 28 TIMACSTIMACS TIMACS Steering CommitteeTIMACS Steering Committee A. A. AvezumAvezum BrazilBrazilC. C. MorilloMorillo - - Columbia Columbia J-P. J-P. BassandBassand FranceFranceL. L. PiegasPiegas BrazilBrazil W. W. BodenBoden USAUSAJ. J. ProbstfieldProbstfield USAUSA J. Col J. Col BelgiumBelgiumS. S. QiaoQiao - - ChinaChina R. Diaz R. Diaz ArgentinaArgentinaH-J H-J RupprechtRupprecht GermanyGermany D. D. FaxonFaxon USAUSAP. G. P. G. StegSteg FranceFrance C. Granger C. Granger USAUSAJ-F. J-F. TanguayTanguay- -CanadaCanada C. Joyner -C. Joyner - Canada CanadaP. P. WidimskyWidimsky Czech RepCzech Rep M. M. KendaKenda SloveniaSloveniaJ. J. VarigosVarigos AustraliaAustralia S.S. Mehta Mehta - - Canada CanadaS. S. YusufYusuf - - CanadaCanada T. T. MoccettiMoccetti SwitzerlandSwitzerlandJ. Zhu J. Zhu ChinaChina TIMACSTIMACS Study OrganizationStudy Organization Coordinating Center: PHRI, McMaster University S. Mehta, S. Yusuf, S. Jolly, C. Horsman, S. Chrolavicius, B. Meeks DSMB: P. Sleight (chair), J. Anderson, D. DeMets, D. Johnstone, D. Holmes Adjudication Committee Chair: C. Joyner Coordinator: M. Lawrence TIMACSTIMACS Criteria for Crossover from Delayed Criteria for Crossover from Delayed Group to Early GroupGroup to Early Group RefractoryRefractory ischemia ischemia New MINew MI HemodynamicHemodynamic instability instability Crossover from Early to DelayedCrossover from Early to Delayed: 11.9%: 11.9% Crossover from Delayed to EarlyCrossover from Delayed to Early: 25% : 25% TIMACSTIMACS Interventions and TimingInterventions and Timing EarlyEarly N=1,593N=1,593 DelayedDelayed N=1,438N=1,438 CoronaryCoronary Angiography Angiography (%) (%)97.697.695.595.5 Median time (h Median time (h iqriqr) )14 (3-21)14 (3-21)50 (41-81)50 (41-81) PCI (%)PCI (%)59.659.655.055.0 Median time (h Median time (h iqriqr) )16 (3-23)16 (3-23)52 (41-101)52 (41-101) CABG (%)CABG (%)14.714.713.613.6 Median time (d Median time (d iqriqr) )7.7 (4.7-17.4)7.7 (4.7-17.4)10.8 (6.7-19.8)10.8 (6.7-19.8) Iqr=interquartile range TIMACSTIMACS Baseline CharacteristicsBaseline Characteristics EarlyEarly N=1,593N=1,593 DelayedDelayed N=1,438N=1,438 AgeAge65.8 % Female% Female34.834.834.734.7 DiabetesDiabetes26.526.527.327.3 Prior MIPrior MI19.719.720.920.9 Prior PCIPrior PCI13.813.814.114.1 Prior CABGPrior CABG7.07.07.37.3 Prior StrokePrior Stroke7.5 IschemicIschemic ECG ECG 80.580.579.979.9 Elevated BiomarkerElevated Biomarker77.277.276.976.9 TIMACSTIMACS In-Hospital MedicationsIn-Hospital Medications EarlyEarly N=1,593N=1,593 DelayedDelayed N=1,438N=1,438 ASAASA98.098.098.198.1 ThieonopyridineThieonopyridine87.287.286.786.7 ThienopyridineThienopyridine or GP or GP IIbIIb/ /IIIaIIIa inhibitor inhibitor 88.288.288.488.4 GP GP IIbIIb/ /IIIaIIIa Inhibitor Inhibitor22.5 AnticoagulantAnticoagulant UFHUFH24.624.624.624.6 LMWHLMWH64.064.064.664.6 FondaparinuxFondaparinux41.941.941.341.3 BivalirudinBivalirudin0.4 Beta BlockerBeta Blocker86.886.886.986.9 StatinStatin85.085.084.384.3 TIMACSTIMACS Primary and Secondary OutcomesPrimary and Secondary Outcomes EarlyEarly N=1,593N=1,593 DelayedDelayed N=1,438N=1,438 HR HR 95% CI95% CI P P Death, MI, Stroke9.79.711.411.40.850.850.68-1.060.68-1.060.150.15 Death, MI, refractory ischemia 9.69.620.720.58-0.890.58-0.890.0020.002 Death, MI, Stroke, refractory ischemia + repeat intervention 16.716.719.719.70.840.840.71-0.990.71-0.990.0390.039 Death6.00.810.810.60-1.110.60-9 MI5.80.830.830.61-1.140.61-5 Stroke1.40.900.900.48-1.680.48-1.680.740.74 Ref. Ischemia1.01.000.300.17-0.530.17-0.53= 3 g/dL2.32.6 Transfusion 2 U2.22.9 TIMACSTIMACS Pre-specified SubgroupsPre-specified Subgroups Overall Age =65 Female Male No ST deviation ST deviation No elevated marker Elevated Marker GRACE 0-140 GRACE =141 3031 1293 1736 1052 1976 1523 1508 668 2363 2070 961 9.7 6.5 12.3 9.7 9.8 7.6 11.7 10.5 9.5 7.7 14.1 0.463 0.540 0.722 0.423 0.0097 0.85 ( 0.68 - 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-Value 0.33 0.5 0.7 1.00 1.52.0 3.0 Early better Delayed better Hazard Ratio (95% CI) Early % 11.4 6.5 14.8 12.3 10.9 8.7 14.3 10.5 11.7 6.7 21.6 Delayed % TIMACSTIMACS GRACE Risk Score: Primary OutcomeGRACE Risk Score: Primary Outcome HR 1.14 95% CI 0.82-1.58 P=0.43 HR 0.65 95% CI 0.48-0.88 P=0.005 Interaction P=0.0097 Low/Int Risk GRACE Score = 140 N=961 Death, MI or Stroke at 6 mo. TIMACSTIMACS ConclusionsConclusions Overall, we found no significant difference 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 stroke The early invasive 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 strategies TIMACSTIMACS ImplicationsImplications 1.Most patients with ACS can be managed safely with either an early or a delayed invasive strategy 2.In 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 possible 3.In all other patients, the decision regarding timing of intervention can depend on other factors, such as cath lab availability and economic considerations. TIMACS An 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 TIMACS An International Randomized Trial of Early Versus Delayed Invasive Strategies in Patients 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 TIMACS An International Randomized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes 180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） TIMACS An International Randomized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes 180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） TIMACS An International Randomized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes * * *P0.05 TIMACS An International Randomized Trial of Early Versus Delayed Invasive Strategies in Patients with Non-ST Segment Elevation Acute Coronary Syndromes 30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） TIMACS A