STEMI: Guidelines Udate 2009 and Clinical Practice

STEMI: Guidelines Udate 2009 and Clinical Practice

Yuejin Yang MD, PhD, FACC

Cardiovascular Institute and Fu-wai Hospital,CAMS & PUMC

冰城国际心血管病会议，哈尔滨 , China, 2010-09-04

急性冠脉综合症（ ACS ）

• 心源性猝死（ SCD ）

• ST 段抬高型急性心肌梗死（ STEMI ）

• 非 ST 段抬高型急性心肌梗死（ NSTEMI ）

• 不稳定型心绞痛（ UA ）

是冠心病致死和致残的主要原因！

Acute Coronary Syndromes (ACS)

Van de Werf F. Throm Haemost. 1997; 78(1):210-213.

NSTEMI STEMI

ACUTE CORONARY SYNDROMESACUTE CORONARY SYNDROMESACUTE CORONARY SYNDROMESACUTE CORONARY SYNDROMES

NQWMIUA QwMI

Tn

CK-MB

ST-elevation ACSST-elevation ACSST-elevation ACSST-elevation ACSNon–ST-elevation ACSNon–ST-elevation ACSNon–ST-elevation ACSNon–ST-elevation ACS

UAUAUAUA NSTEMINSTEMINSTEMINSTEMI STEMISTEMISTEMISTEMI

Thrombus Formation and Thrombus Formation and ACSACS

UA NQMINQMI STE-MISTE-MI

Plaque Disruption/Fissure/Erosion

Thrombus Formation

Non-ST-Segment Elevation Non-ST-Segment Elevation Acute Coronary Syndrome Acute Coronary Syndrome (ACS)(ACS)

ST-ST-Segment Segment Elevation Elevation Acute Acute Coronary Coronary Syndrome Syndrome (ACS)(ACS)

Old Terminology:

NewTerminology:

Thrombus

MicrovascularMicrovascularObstructionObstruction

Platelet-thrombin micro-emboliPlaque rupture

1st1st 2nd2nd 3rd3rd

CK-MBCK-MB

CK-MBCK-MBCK-MB

Cutoff TnT CurveTnT Curve

embolus embolus embolus

Inflammation, spasm endothelial dysfunction

ACS PathophysiologyACS PathophysiologyPlaque rupture, thrombosis and Plaque rupture, thrombosis and

microembolizationmicroembolization

泡沫泡沫细胞细胞

脂质脂质条纹条纹

间质间质损害损害

粥样粥样斑块斑块

纤维化纤维化斑块斑块

多重损伤多重损伤// 破裂破裂

内皮功能障碍内皮功能障碍

平滑肌和胶原平滑肌和胶原

从第一个从第一个 1010 年年从第三个从第三个 1010 年年从第四个从第四个 1010 年年

进展主要由于：脂质聚集进展主要由于：脂质聚集血栓形成血栓形成 ,,血肿血肿

Adapted from Stary HC et al. Adapted from Stary HC et al. CirculationCirculation. 1995;92:1355-1374.. 1995;92:1355-1374.

动脉粥样硬化病变进展和急性变化

外膜

稳定型斑块（病变）

纤维帽( 平滑肌细胞和基质 )

脂质核

内皮细胞内膜平滑肌细胞

( 修复型 )

中层平滑肌细胞( 可伸缩型 )

外膜

lipid core脂质核

不稳定（易损）性斑块（病变）

发生在破裂 / 侵蚀口的血小板凝聚

血小板聚集形成血栓

血小板的粘附和激活血流中的正常血小板

血小板粘附于损伤的内皮表面并被激活

血小板

内皮细胞内皮下腔

血小板粘附到内皮下腔

血小板血栓

血小板（白色）血栓部分堵塞冠脉：UA/NSTEMI

血小板（白色）血栓部分堵塞冠脉：UA/NSTEMI

通常为富含血小板的血栓部分阻塞血管所引起

Unobstructedlumen

thrombus

斑块破裂处由 GP IIb-IIIa 受体的作用使纤维蛋白原交联结合

血小板

纤维蛋白原

斑块破裂

GP IIb-IIIa

血管壁

纤维蛋白（红色）血栓堵死冠脉：STEMI

1. Adapted from Antman EM. In: Califf RM, ed. Atlas of Heart Diseases, VIII. Philadelphia, PA: Current Medicine, 1996.

斑块破裂处 : 血小板血栓进一步

形成纤维蛋白血栓 : 急闭冠脉

血小板

红细胞

纤维蛋白网

GPIIb/IIIa

通常是由冠状动脉内完全闭塞性血栓造成的

RBC= 红细胞

仅限内部使用

Pathophysiology of STEMI

Modified with permission from Libby Circulation.2001; 104: 365-372.

1 65432

Management Before STEMI

Onset of STEMI• Prehospital issues•Initial recognition and management in the Emergency Department•Reperfusion

Hospital Management•Medications•Arrhythmias•Complications•Preparation for discharge

Secondary Prevention/Long-Term Management

ST 抬高心肌梗死不稳定性心绞痛 / 非ST 段抬高心肌梗死

17

1990199219941996199820002002

1990ACC/AHA

AMI R.

Gunnar

1994AHCPR/NHLBI

UA E. Braunwald 1996 1999

Rev Upd ACC/AHA AMI T. Ryan

2004 2007 Rev Upd ACC/AHA STEMI E. Antman

2000 2002 2007 Rev Upd RevACC/AHA UA/NSTEMI E. Braunwald; J. Anderson

20042007

Evolution of Guidelines for ACS

2009

2009Upd

ACC/AHA STEMI/PCIF. Kushner

ACC/AHAACC/AHA 2004 2004 STEMI Gudelines STEMI GudelinesACC/AHA 2007ACC/AHA 2007 STEMI GUIDELINES STEMI GUIDELINES

NACB 2007NACB 2007 guidelines for ACS guidelines for ACS ESC-ACCF-AHA-WHFESC-ACCF-AHA-WHF Universal Universal Definition -2007 Definition -2007 ACC/AHAACC/AHA 2008 Care Metrics for AMI2008 Care Metrics for AMIESC 2008ESC 2008 STEMI guidelinesSTEMI guidelinesACC/AHA 2009 STEMI/PCI Guidelines Focused Update

STEMI: Guidelines and Updates

STEMI Guidelines

• 2004: Matured and evidence-based

• 2007: Revised and supplement

• 2009: Updated according to new

further evidences (clinical trials)

What is a Myocardial Infarction?

• WHO Definition –1979

• ESC-ACC Redefinition –2000

• ESC-ACCF-AHA-WHF Universal Definition -2007

WHO Definition –1979

The Criteria for the diagnosis of acute MI included 2 of the following 3:

• History: Chest discomfort or equivalent

• Diagnostic changes on ECG

• Elevated cardiac enzymes (or markers)

Myocardial Infarction: 2000 Redefined

Why redefine myocardial infarction? • The arrival of the highly sensitive/specific troponin

in routine clinical use.• Clinicians were defining MI differently even within

the same hospital.• Hospitals were defining MI differently even within

the same city.• Clinical trials defined MI differently.• Previous assays in definitions were confusing and

inaccurate.

JACC: 2000; 36: 959-969 and the EHJ: 2000; 21:1502-1513.

• Biomarker indicators of MI • Troponin is preferred biomarker for dx of MI • cTnT or cTnI > 99th %ile on any determination • CK-MB > 99th %ile on two successive

measurements or > 2X ULN on any sample

----------------------------REFERENCE LABORATORIES---------------------------- cTnI 0 - 0.0812/04 0.13*# 1:03A (1) (1) >0.08 INDICATIVE OF MYOCARDIAL INJURY; NOTE NEW REFERENCE RANGEPress <Enter> to continue: or "P" to print screen :

Redefinition of MI

• The new definition for MI is consistent with the pathological definition: The new definition seeks to identify the presence of myocardial necrosis in an appropriate clinical setting by measuring highly accurate blood levels of biomarkers of myocardial necrosis.

What was lacking in the 2000 Redefinition of MI ?

Non-invasive imaging not considered diagnostic

No information for pts following CABG

Microinfarction After Percutaneous Coronary Intervention Associated With Mild Creatine Kinase-MB Elevation

Ricciardi et al. Circulation 2001. 103:2780

ESC-ACC Redefinition

Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following:

– Ischemic symptoms– Development of Q waves on the ECG– ECG changes indicative of ischemia– Coronary artery intervention

• Biomarker rise further defined as above the 99% of normals with acceptable (<10%) precision

Subsets of AMI(2007):Additional Classifications

• Type 1: Spontaneous & Primary coronary event,

CA sclerotic- & thrombotic-related • Type 2: Non-spontaneous & Secondary event,

CA sclerotic but non-thrombotic- related, or non-CA sclerotic-related

• Type 3: SCD• Type 4: PCI-related

4a: CA Embolic- & acute closure related

4b: Stent thrombosis related• Type 5: CABG-related

Diagnosis of myocardial infarction

• Cardiac troponin is the preferred marker for the diagnosis of MI

• Creatine kinase MB (CK-MB) by mass assay is an acceptable alternative when cardiac troponin is not available

Class I, Level of Evidence A


• Total CK, CK-MB activity, AST, and/or LDH should not be used as biomarkers for the diagnosis of MI

Class III, Level of Evidence C

Early Risk Stratification - cTn

In patients with a clinical syndrome consistent with ACS, a maximal (peak) concentration exceeding the 99th percentile of values for a reference control group should be considered indicative of increased risk of death and recurrent ischemic events

Class I, Level of Evidence A


Use of total CK for diagnosis of MI is not recommended!

However,

in the absence of availability of data using a troponin or CK-MB assay (mass or activity), when only total CK values are available, the recommended decision-limit is 2 times the sex-specific upper reference limit. A rise and/or fall of CK-MB or total CK provides additional evidence supporting the diagnosis of acute MI.

Myocardial Infarction:Definition?

• WHO: Definition (1979) Basic definition ( 基础诊断标准 )• ESC/ACC: Redefinition (2000) Unifying definition ( 统一诊断标准 )• ESC/ACCF/AHA/WHF: Universal Definition

(2007) Refined & improved definition ( 细化而完善的诊断标准 )

AMI 的诊断依据• 心肌坏死证据特异性生物标志物 (ESC/ACC,2000) TnT ， TnI; CK-MB, T-CK; SGOT, LDH1, Hb et. 临床特征性表现 (WHO, 1979) ECG 特征性改变 (WHO,1979)

影像学特征性改变 (ESC/ACC/AHA,2007) ECHO ， MRI ， CT, SPECT, et. 造影下冠脉狭窄或堵塞

ST 抬高型急性心肌梗塞（ STEMI ）的诊断

• 国际诊断标准（ WHO ）： 2/3 条件

典型的临床表现

ECG 动态演变有任何 2 个均可确诊

心肌酶异常

• 临床表现 : 持续胸痛 >30 ’, 伴出汗、恶心呕吐、面色苍白，

含 NTG 1-2 ＃不缓解 ;

• ECG: 前壁、下后壁导联 ST 或 CLBBB, 即可确诊。

• 酶学结果 : 临床上最次要 , 诊断不及时 .

只有症状或 ECG 不典型时，方有参考价值。

AMI 的特殊表现

• 以心衰肺水肿为首发表现－大缺血，小梗死

• 以晕厥为首发表现－ AVB 伴大汗、面色苍白、 HR30

－ 40bpm, 见于心肌梗死初起 .

• 以心源性休克为首发表现－ BP 、面色苍白，皮肤湿

冷， HR

• 以上腹痛为首发表现－伴恶心、呕吐、大汗淋漓

AMI 的鉴别诊断• 主动脉夹层动脉瘤 :

胸痛剧烈，无 ECG 变化• 心绞痛 : 胸痛 <30 ’

NIG 可缓解不伴恶心呕吐• 急性肺栓塞 : ECG

　　　酷似 NSTEMI

SI QIII TIII

• 气胸 : CXR 可鉴别• 心包炎、心肌炎 :

ECG广泛 ST 上抬• 急腹症 : 有腹部体征 ECG无变化• 应急性心肌病 :

　　　　应激发病 IRCA 通畅可逆性大室壁瘤

Management of STEMI

STEMI 的病理生理和治疗原则

• 病理生理：

• 治疗原则：首选冠脉再通治疗（溶栓、 PCI 或 CABG ）恢复心肌血流和再灌注

斑块破裂血栓形成

冠脉急性闭塞

心肌坏死

AMI 的治疗原则

• 持续心电监测，及时发现和处理心律失常• 维持血液动力学稳定• 抗血小板抗凝

• 尽快给予再灌注治疗，• 使闭塞的 IRCA迅速再通• 降低心肌耗氧量，保护缺血心肌。• 稳定易损斑块 .

AMI治疗 : 急救成效

• AMI 的两大死因：心律失常（如 Vf ）和泵衰竭（心衰和休克）；• 过去 30 年来， AMI治疗进展和巨大 :

CCU 的建立 : 除颤、心电和血液动力学监测 ,

药物 : -B 、硝酸酯、抗血小板制剂 ,ACEI 和他丁类

再灌注治疗 : 巨大突破 ,溶栓和 PCI；• 30天病死率 :CCU 前期 30％ CCU期的 15％再灌注时期的 5％。

AMI 的治疗流程• 再灌注治疗 : 首选溶栓（ IV ） -- r-tPA U.K r.S.K

急诊 PCI• 一般治疗：心电血压监测、建立 iv 通道 , 镇痛、吸氧 , 溶栓或 PCI 准备• 药物治疗：硝酸酯、 -B 、 ACEI 、抗血小板、抗凝剂 ,他类；• 并发症治疗：心律失常低血压心力衰竭心源性休克机械并发症梗塞后心绞痛再梗塞• 恢复期（出院前）治疗－血运重建术（ PCI 、 CABG ）

药物治疗

• 硝酸酯• - 受体阻滞剂无禁忌症者均必须使用• ACEI 、 ARBS

• 抗血小板、抗凝• 镁制剂、钙拮抗剂：必要时使用• G-I-K ：可用可不用，最好不用• 降脂药 : 他丁类

4. 4. 降降胆固醇、稳定、稳定斑块斑块抗炎症抗炎症 (hs-CRP)(hs-CRP) 、感染、感染 ((他汀类他汀类 ))

1.1. 抗血小板粘附 / / 激活作用 // 聚集反应

(ASA, (ASA, 抵克力得，氯吡抵克力得，氯吡格雷，格雷， IIb/IIIa IIb/IIIa 抑制剂抑制剂 ))

2. 2. 抗抗凝血酶 ((肝素肝素 // 低份子肝素低份子肝素 ))

3.3. 抗抗心肌缺血、减少、减少坏死面积 (( 受体阻滞剂、、硝酸盐类等 ))

血小板

IIb/IIIa 受体

人纤维蛋白原凝血酶

纤维蛋白凝块

ACS 的药物治疗及其作用机制

Therapeutic objective Therapeutic objective of of STEMI STEMI (ESC 200(ESC 20088))

• The present guidelines pertain to patients The present guidelines pertain to patients presenting with ischemic symptoms and persistent presenting with ischemic symptoms and persistent ST-segment elevation on the ECG (STEMI). The ST-segment elevation on the ECG (STEMI). The great majority of these patients will show a typical great majority of these patients will show a typical rise of biomarkers of myocardial necrosis and rise of biomarkers of myocardial necrosis and progress to Q-wave myocardial infarction. progress to Q-wave myocardial infarction.

• TTherapeutic objectiveherapeutic objective is to achieve is to achieve rapid, rapid, complete, and sustained reperfusioncomplete, and sustained reperfusion by by primary primary angioplasty or fibrinolytic therapy angioplasty or fibrinolytic therapy

2004 年 ACC/AHA STEMI指南

• 再灌注治疗目标：应在发病 120’ 内完成溶栓：应在 30’ 内开始（ door to-heedle tuise ＜ 30’ ） PCI ：应在 90’ 内完成（ door to-telloon time ＜ 90’ ）主张：应将患者尽快转运到有条件医院行急诊 PCI

强调：越快越好，争分夺秒，不得怠慢！时间就是心肌，就是生命，不得耽搁！

• 依据：大量循证医学证据（研究结果）

Antman EM, et al.Circulation. 2004 Aug 3;110(5):588-636.Antman EM, et al.Circulation. 2004 Aug 3;110(5):588-636.

Options for Transport of STEMI Patients and Initial Reperfusion Treatment Goals

EMS Transport

Onset of symptoms of

STEMI

EMSDispatch

EMS on-scene• Encourage 12-lead ECGs.• Consider prehospital fibrinolytic if

capable and EMS-to-needle within 30 min.

GOALS

PCIcapable

Not PCIcapable

Hospital fibrinolysis:

Door-to-Needle

within 30 min.

EMS Triage Plan

Inter-HospitalTransfer

Golden Hour = first 60 min. Total ischemic time: within 120 min.

Patient EMS Prehospital fibrinolysisEMS-to-needlewithin 30 min.

EMS transportEMS-to-balloon within 90 min.

Patient self-transport Hospital door-to-balloon

within 90 min.Dispatch

1 min.

5 min.

8 min.

Circulation. 2008;117:296-329. JACC. 2008;51:210-247.

• Patients receiving fibrinolysis should be risk-stratified to identify need for further revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG).

• All patients should receive late hospital care and secondary prevention of STEMI.

Fibrinolysis

Primary PCI

Noninvasive Risk Stratification

LateHospital Care

and SecondaryPrevention

PCI or CABG

NotPCI Capable

PCI Capable

Rescue Ischemiadriven

Options for Transport of Patients With STEMI and Options for Transport of Patients With STEMI and Initial Reperfusion TreatmentInitial Reperfusion Treatment

Laboratory ExaminationsLaboratory Examinations

Laboratory examinations should be performed as part of the

management of STEMI patients, but should not delay the

implementation of reperfusion therapy.

Serum biomarkers for cardiac damage Complete blood count (CBC) with platelets International normalized ratio (INR) Activated partial thromboplastin time (aPTT) Electrolytes and magnesium Blood urea nitrogen (BUN) Creatinine Glucose Complete lipid profile

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Cardiac-specific troponins should be used as the

optimum biomarkers for the evaluation of patients

with STEMI who have coexistent skeletal muscle

injury.

For patients with ST elevation on the 12-lead ECG

and symptoms of STEMI, reperfusion therapy

should be initiated as soon as possible and is not

contingent on a biomarker assay.

Biomarkers of Cardiac DamageBiomarkers of Cardiac Damage



Patients with STEMI should have a portable chest

X-ray, but this should not delay implementation of

reperfusion therapy (unless a potential

contraindication is suspected, such as aortic

dissection).

Imaging studies such as a high quality portable chest

X-ray, transthoracic and/or transesophageal

echocardiography, and a contrast chest CT scan or

an MRI scan should be used for differentiating STEMI

from aortic dissection in patients for whom this

distinction is initially unclear.

ImagingImaging



2005 年 ESC PCI 指南• 将 PCI 作为 STEMI治疗的首要和最终目标• 也是循证的结果

Siber S,et al. Eur Heart J 2005;26:804-847

53

Primary PCIPrimary PCI

STEMI:PCI

• 机械开通闭塞冠脉，尽快恢复血流，技术成熟• 分为四类：

直接 PCI （不先溶栓）显著获益（ IA ）挽救 PCI （溶栓未通者）有获益（ IB ）

立即 PCI （溶栓已通者）无获益有害延迟 PCI （溶栓后 1-7天）获益（ IA ）

晚期 PCI (late PCI): 错过溶栓者，遭质疑

转院 PCI------优于溶栓治疗

• DANAMI-2 研究（ n=1572 ） Thrombolysis （ rtPA ） /PCI ： n=782/790

ED-PCI mean delay ： referral hosp 90’ （ 74-108 ）

PCI Centers 63’ （ 49-77 ）

ED-Thrombolysis delay ： referral hosp 20 （ 15-30 ）

PCI Centers 20 （ 13-30 ）

30-day end point （ D/MI/Stroke ）： 13.7%/8.0%

56

Primary PCI

STEMI patients presenting to a hospital STEMI patients presenting to a hospital with with PCI capabilityPCI capability should beshould be treated with treated with primary PCIprimary PCI within 90 min of first medical within 90 min of first medical contact as a systems goal.contact as a systems goal.

STEMI patients presenting to a hospital STEMI patients presenting to a hospital without PCI capabilitywithout PCI capability, and who cannot be , and who cannot be transferred to a PCI center and undergo transferred to a PCI center and undergo PCI within 90 min of first medical contact, PCI within 90 min of first medical contact, should be treated with should be treated with fibrinolyticfibrinolytic therapy therapy within 30 min within 30 min of hospital presentation as a of hospital presentation as a systems goal, unless fibrinolytic therapy is systems goal, unless fibrinolytic therapy is contraindicated.contraindicated.



Symptoms to balloon inflation (minutes)Symptoms to balloon inflation (minutes)

On

e-ye

ar m

ort

alit

y, %

On

e-ye

ar m

ort

alit

y, %

6 RCTs of Primary PCI by Zwolle Group 1994 – 20016 RCTs of Primary PCI by Zwolle Group 1994 – 2001N = 1791N = 1791

RR = 1.08 [1.01 RR = 1.08 [1.01 – – 1.16] for each 30 min delay1.16] for each 30 min delay((PP = 0.04) = 0.04)

PP < 0.0001 < 0.00011212

1010

88

66

44

22

0000 6060 120120 180180 240240 300300

360360

Symptom Onset to Balloon Time and Symptom Onset to Balloon Time and Mortality in Primary PCI for STEMIMortality in Primary PCI for STEMI

DeLuca et al. Circulation 2004;109:1223.

Boersma. Eur Heart J 2006;27:779-788.

Primary PCI vs. Fibrinolysis: Importance of Time

For every 10 min delay to PCI: 1 % reduction in Mortality

Difference

N= 7419

Relationship Between PCI Related Time Delay and Mortality

Nallamothu BK. Am J Cardiol 2003;92:824-826.

Options for Transport of Patients With STEMI and Initial Reperfusion Treatment

EMS Transport

Onset of symptoms of

STEMI

9-1-1EMS

Dispatch

EMS on-scene• Encourage 12-lead ECGs.• Consider prehospital fibrinolytic if

capable and EMS-to-needle within 30 min.

GOALS

PCIcapable

Not PCIcapable

Hospital fibrinolysis:

Door-to-Needle

within 30 min.

EMS Triage Plan

Inter-HospitalTransfer

Golden Hour = first 60 min. Total ischemic time: within 120 min.

Patient EMS Prehospital fibrinolysisEMS-to-needlewithin 30 min.

EMS transportEMS-to-balloon within 90 min.

Patient self-transport Hospital door-to-balloon

within 90 min.Dispatch

1 min.

5 min.

8 min.

Antman EM, et al. J Am Coll Cardiol 2008. Published ahead of print on December 10, 2007. Available at http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001. Figure 1.

http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001

61

Facilitated PCIFacilitated PCI

Meta-analysis: Facilitated PCI vs Primary PCI

1.03(0.15-7.13)

3.07(0.18-52.0)

1.43(1.01-2.02)

1.03

(0.49-2.17)

Mortality Reinfarction Major Bleeding

Fac. PCIBetter

PPCIBetter

Fac. PCIBetter

PPCIBetter

Fac. PCIBetter

PPCIBetter

Keeley E, et al. Lancet 2006;367:579.

0.1 1 10 0.1 1 10 0.1 1 10

1.38 (1.01-1.87)

1.71 (1.16 - 2.51)

1.51 (1.10 - 2.08 )

Lytic alone N=2953

IIb/IIIa alone N=1148

Lytic +IIb/IIIaN=399

All (N=4500)

1.40 (0.49-3.98)

1.81

(1.19-2.77)

A planned reperfusion strategy using full-dose fibrinolytic therapy followed by immediate PCI is not recommended and may be harmful. not recommended and may be harmful.

Facilitated PCI using regimens other than full-dose fibrinolytic therapy mightmight be considered as a reperfusion strategy when all of the following are present:a. Patients are at high risk,b. PCI is not immediately available within 90 minutes, andc. Bleeding risk is low (younger age, absence of poorly controlled hypertension, normal body weight).

Facilitated PCI



Rescue and Late PCIRescue and Late PCI

Wijeysundera HC, et al. J Am Coll Cardiol. 2007;49:422-430.

Meta-analysis: Rescue PCI vs Conservative Tx

Outcome Rescue PCI Conservative Treatment

RR (95% CI) P

Mortality, %(n)

7.3(454)

10.4(457)

0.69(0.46–1.05)

.09

HF, % (n)

12.7(424)

17.8(427)

0.73(0.54–1.00)

.05

Reinfarction,% (n)

6.1(346)

10.7(354)

0.58(0.35–0.97)

.04

Stroke, % (n) 3.4(297)

0.7(295)

4.98(1.10–22.48)

.04

Minor bleeding,% (n)

16.6(313)

3.6(307)

4.58(2.46–8.55)

<.001

In 3 trials, enrolling 700 patients that reported the composite end point of all-cause mortality, reinfarction, and HF, rescue PCI was associated with a significant RR reduction of 28% (RR 0.72; 95% CI, 0.59-0.88; P=.001)

A strategy of coronary angiography with coronary angiography with

intent tointent toperform PCI (or emergency CABG) isperform PCI (or emergency CABG) isrecommended in patients who have receivedrecommended in patients who have receivedfibrinolytic therapyfibrinolytic therapy and have:

a.a.Cardiogenic shock Cardiogenic shock in patients < 75 years who are suitable candidates for revascularization

b. Severe congestive heart failure Severe congestive heart failure and/or pulmonary edema (Killip class III)

c. Hemodynamically compromising ventricular arrhythmias.ventricular arrhythmias.




Rescue PCI

Rescue PCI

A strategy of coronary angiography with intent to perform rescue PCI is reasonable for patients in whom fibrinolytic fibrinolytic therapy has failedtherapy has failed (ST-segment elevation < 50% resolved after 90 min following initiation of fibrinolytic therapy in the lead showing the worst initial elevation) and a moderate or large area of myocardium at risk [anterior MI, inferior MI with right ventricular involvement or precordial ST-segment depression].


PCI of a hemodynamically significant stenosis in a patent infarct artery > 24 hours after STEMI may be considered may be considered as part of a invasive strategy.

PCI of a totally occluded infarct artery > 24 hours after STEMI is not not recommended recommended in asymptomatic patients asymptomatic patients with 1- or 2-vessel disease if they are with 1- or 2-vessel disease if they are hemodynamically and electrically stable hemodynamically and electrically stable and do not have evidence of severe and do not have evidence of severe ischemia. ischemia.

Late PCI after Fibrinolysis or for Patients Not Undergoing Primary Reperfusion



Open Artery Trial (OAT): Death/MI/Class IV CHF

Hochman. NEJM. 2006;355:2395-2407.

70

AnticoagulantsAnticoagulants(Anti-thrombins)(Anti-thrombins)

Anticoagulants

Patients undergoing reperfusion with fibrinolyticsfibrinolytics should receive anticoagulant therapy for a minimum of 48 hours for a minimum of 48 hours (Level of Evidence: C) and preferably for the duration of preferably for the duration of the index hospitalizationthe index hospitalization, up to 8 days (regimens other than unfractionated heparin [UFH] are recommended if anticoagulant therapy is given for more than 48 hours because of the risk of heparin-induced thrombocytopenia with prolonged UFH treatment). (Level of Evidence: A)

Anticoagulant regimens with established efficacy include:♥ UFH (LOE: C)♥ Enoxaparin (LOE:A)♥ Fondaparinux (LOE:B)



ExTRACT-TIMI 25: Primary End Point Death or Nonfatal MI

0

3

6

9

12

15

0 5 10 15 20 25 30

Death

or

Non

fata

l M

I (%

)

Enoxaparin

UFH

Relative Risk0.83 (95% CI, 0.77 to

0.90)P<0.001

Days after Randomization

9.9%

12.0%

Lost to follow-up = 3

17% RRR

Adapted with permission from Antman. N Engl J Med. 2006;354:1477-1488.

Anticoagulants

Because of the risk of catheter thrombosis,catheter thrombosis,fondaparinux should not be used as the fondaparinux should not be used as the solesoleanticoagulant to support PCI. anticoagulant to support PCI. An additionalanticoagulant with anti-IIa activity should beadministered.


It is reasonable for patients with STEMI It is reasonable for patients with STEMI who who do not undergo reperfusion therapydo not undergo reperfusion therapy to be to be treated with treated with anticoagulant therapy (not-anticoagulant therapy (not-UFH regimen) for the duration of the index UFH regimen) for the duration of the index hospitalization, up to 8 dayshospitalization, up to 8 days. .

Convenient strategies that can be used Convenient strategies that can be used include those with include those with LMWHLMWH (Level of (Level of Evidence: C)Evidence: C) or or fondaparinuxfondaparinux (Level of (Level of Evidence: B)Evidence: B) using the same dosing using the same dosing regimens as for patients who receive regimens as for patients who receive fibrinolytic therapy.fibrinolytic therapy.

Anticoagulants




Antiplatelets Antiplatelets

Antiplatelets

Oral antiplatelet therapy:

- Aspirin.

- Thienopyridines: Clopidogrel

Intravenous Antiplatelet Therapy:

(GpIIb/IIIa inhibitors)

- Abciximab (ReoPro).

- Eptifibatide (Integrilin).

- Tirofiban (Aggrastat).

ThienopyridinesThienopyridines

78

It is reasonable to start treatment with glycoprotein IIb/IIIa receptor antagonists at the time of primary PCI (with or without stenting) in selected patients with STEMI:

abciximab

tirofiban and eptifibatide

Use of Glycoprotein IIb/IIIa Receptor Antagonists in STEMI



Modified Recommendation

CLARITY-TIMI 28 Primary Endpoint:Occluded Artery (or D/MI thru Angio/HD)

PlaceboClopidogrelLD 300 mgMD 75 mg

P=0.00000036P=0.00000036

Odds Ratio 0.64(95% CI 0.53-0.76)

Odds Ratio 0.64(95% CI 0.53-0.76)

Clopidogrelbetter

Placebobetter

n=1752 n=1739

Sabatine N Eng J Med 2005;352:1179.

STEMI, Age 18-75

15.0

21.7

0

5

10

15

20

25

Occ

lud

ed A

rter

y o

r D

eath

/MI

(%)

1.00.4 0.6 0.8 1.2 1.6

36%Odds

Reduction

36%Odds

Reduction

De

ad

(%

)

Days Since Randomization (up to 28 days)

Placebo + ASA: 1,846 deaths (8.1%)

Clopidogrel + ASA:1,728 deaths (7.5%)

0.6% ARD7% RRR P = 0.03

N = 45,852 No Age limit ; 26% > 70 y

Lytic Rx 50%

No LD given

COMMIT: Effect of CLOPIDOGREL on Death In Hospital

Chen ZM, et al. Lancet. 2005;366:1607.

Clopidogrel 75 mg per day orally should be Clopidogrel 75 mg per day orally should be added to aspirin in patients with STEMadded to aspirin in patients with STEMI I regardless of whether they undergo regardless of whether they undergo reperfusion with fibrinolytic reperfusion with fibrinolytic therapy or do therapy or do not receive reperfusion therapy. not receive reperfusion therapy.

Treatment with Treatment with clopidogrel clopidogrel should continue should continue for at for at least 14 days.least 14 days.

Thienopyridines



In patients < 75 yearsIn patients < 75 years who receive who receive fibrinolytic therapy or who do not fibrinolytic therapy or who do not receive reperfusion therapyreceive reperfusion therapy, it is , it is reasonable to administer an reasonable to administer an oral oral clopidogrel loading dose of 300 mgclopidogrel loading dose of 300 mg. (No . (No data are available to guide decision making data are available to guide decision making regarding an oral loading dose in patients regarding an oral loading dose in patients ≥ 75 years of age.)≥ 75 years of age.)

Long-term maintenance therapy (e.g., 1 Long-term maintenance therapy (e.g., 1 year) with clopidogrel (75 mg per day year) with clopidogrel (75 mg per day orally)orally) can be useful in STEMI patients can be useful in STEMI patients regardless of whether they undergo regardless of whether they undergo reperfusion with fibrinolytic therapy or do reperfusion with fibrinolytic therapy or do not receive reperfusion therapy.not receive reperfusion therapy.


Thienopyridines


Glycoprotein IIb/IIIa InhibitorsGlycoprotein IIb/IIIa Inhibitors

It is reasonable to start treatment with

abciximab as early as possible before primary

PCI (with or without stenting) in patients with

STEMI.

Treatment with tirofiban or eptifibatide may

be considered before primary PCI (with or

without stenting) in patients with STEMI.



STEMI: Guideline Update ?

• PCI related clinical evidence supplements

85

Recommendations for the Use of Glycoprotein IIb/IIIa Receptor Antagonists in

STEMI

86

It is reasonable to start treatment with glycoprotein IIb/IIIa receptor antagonists at the time of primary PCI (with or without stenting) in selected patients with STEMI:

abciximab

tirofiban and eptifibatide





87


Grum et al. Small Molecule GP IIb/IIIa Inhibitors primary PCI.Circ Cardiovas Intervent. 2009;2:230-2236.

Study Name Year Statistics p-value

Dead/Total

SMGPI

Abciximab

Valgimigli 2005 0.667 (0.11-4.09)

0.661 2/87 3/88

EVA-AMI 2007 1.017 (0.36-2.86)

0.974 8/226

7/201

MULTISTRATEGY 2008 0.438 (0.13-1.44)

0.173 4/372

9/372

FATA 2008 1.367 (0.43-4.35)

0.596 7/351

5/341

0.843 (0.46-1.55)

0.584

0.1 0.2 0.5 1 2 5

Favors SM GPI Favors Abciximab

OR and 95% CI of 30-day Mortality

88


III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIIIThe usefulness of glycoprotein IIb/IIIa

receptor antagonists (as part of a

preparatory pharmacologic strategy for

patients with STEMI prior to arrival in

the cardiac catheterization laboratory

for angiography and PCI) is uncertain.


89

FINESSE: Study design

Ellis et al. N Eng J Med. 2008;358:2205-2217.

TreatmentPre-PCI treatment with ½ -dose lytic plus abciximab, pre-PCI abciximab alone, and abciximab at time of PCI

InclusionSuspected acute MI (ST change or LBBB) within 6 h of symptom onset

ExclusionLow risk (<60 yo, localized inferior infarct) high risk for bleeding

1° OUTCOMES Death, VF after 48 hours, shock, CHF within 90 days

90

Primary, secondary, and bleeding end points in FI NESSEEnd point Primary

PCI (% )Abciximab-facilitated (% )

Combination (abciximab/reteplase)-facilitated (% )

p, combination-facilitated vsprimary PCI

p, combination-facilitated vsabciximab-facilitated

Primary end point* at 90 days

10.7 10.5 9.8 NS NS

>70% ST segment resolution within 60– 90 min

31.0 33.1 43.9 0.003 0.01

TIMI major or minor bleeding through discharge or day 7

6.9 10.1 14.5 <0.001 0.008

End point Primary PCI (% )

Abciximab-facilitated (% )

Combination (abciximab/reteplase)-facilitated (% )

p, combination-facilitated vsprimary PCI

p, combination-facilitated vsabciximab-facilitated

Primary end point* at 90 days

10.7 10.5 9.8 NS NS

>70% ST segment resolution within 60– 90 min

31.0 33.1 43.9 0.003 0.01

TIMI major or minor bleeding through discharge or day 7

6.9 10.1 14.5 <0.001 0.008

* All-cause mortality; rehospitalization or emergency department treatment for CHF; resuscitated ventricular fibrillation occurring >48 hours after randomization; cardiogenic shock

Ellis et al. N Eng J Med. 2008;358:2205-2217

91

OnTIME 2: Study design

Acute myocardial infarctionAcute myocardial infarctiondiagnosed in ambulance or referral centerdiagnosed in ambulance or referral center

ASA+600 mg ClopidogrelASA+600 mg Clopidogrel

AngiogramAngiogram

Tirofiban *Tirofiban *PlaceboPlacebo

TransportationTransportation

PCI centrePCI centreAngiogramAngiogram

TirofibanTirofibanprovisionalprovisional

Tirofiban Tirofiban cont’dcont’d

PCIPCI

van’t Hof et al. Lancet 2008;372:537-46.

92

OnTIME 2: endpoints

Primary

• Residual ST segment deviation (>3mm) 1 hour after

PCI

Key Clinical Secondary

• Combined occurrence of death, recurrent MI, urgent

TVR or thrombotic bailout at 30 days follow-up

• Safety (major bleeding)

• Death at 1 year follow-up

93

On-TIME 2: Results

van’t Hof et al. Lancet 2008;372:537-46

Residual ST Deviation after PCI

p=0.003 3.6± 4.6mm 4.8± 6.3mm

94

On-TIME 2: Results

van’t Hof et al. Lancet 2008;372:537-46.

Event-free Survival at 30 days

Clinical outcome Placebo tirofiban P-value

Death/recurrent MI or urgent TVR

39/477 (8.2%)

33/473 (7.0%)

0.485

95

BRAVE 3: Study design

Mehilli et al. Circ. 2009;119:1933-1940

TREATMENT: pre-PCI treatment with clopidogrel (600 mg), followed by abciximab vs. placebo

INCLUSION: suspected acute MI (ST change or LBBB) within 24 h of symptom onset

EXCLUSION: high risk for bleeding, prior stroke,shock,trauma, thrombolytics, hypertension,relevant hematologic deviations

1° OUTCOMES: infarct size, death, stroke, urgent revascularization of affected artery

96

Effects of Abciximab

Mehilli et al. Circ. 2009;119:1933-1940

No significant difference in infarct size or major bleeding

P= 0.47

P= 0.40

97

Recommendations for the use of

Thienopyridines

98

Loading doses for Thienopyridines in Patients with Acute

Coronary Syndromes (STEMI and UA/NSTEMI)

99

Recommendations for the use of Thienopyridines

A loading dose of thienopyridine is recommended for

STEMI patients for whom PCI is planned. Regimens

should be one of the following:

MODIFIED Recommendation

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIIIClopidogrel at least 300 mg to 600mg† should be given as early as possible before or at the time of primary or non-primary PCI.

100

• The optimal loading dose of clopidogrel has not been established

• Randomized clinical trials using >300mg of clopidogrel as a loading dose for PCI in STEMI or UA/NSTEMI have not rigorously established superior safety or efficacy

• Clopidogrel is a prodrug which must undergo hepatic conversion to its active metabolite for platelet inhibition, a process taking several hours.


101


Prasugrel 60 mg should be given

as soon as possible for primary

PCI.



102

TRITON-TIMI 38:Study Design

Double-blind

ACS (STEMI or UA/NSTEMI) & Planned PCI

ASA

PRASUGREL60 mg LD/ 10 mg MD

CLOPIDOGREL300 mg LD/ 75 mg MD

1o endpoint: CV death, MI, Stroke2o endpoints: CV death, MI, Stroke, Rehosp-Rec Isch

CV death, MI, UTVR Stent Thrombosis (ARC definite/prob.) Safety endpoints: TIMI major bleeds, Life-threatening bleedsKey Substudies: Pharmacokinetic, Genomic

Median duration of therapy - 12 months

N= 13,600

Wiviott SD et al AHJ 152: 627,2006Adapted with permission from E.Antman

103

0

5

10

15

0 30 60 90 180 270 360 450

HR 0.81(0.73-0.90)P=0.0004

Prasugrel

Clopidogrel

Days

En

dp

oin

t (%

)

12.1

9.9

HR 1.32(1.03-1.68)

P=0.03

Prasugrel

Clopidogrel1.82.4

138 events

35 events

Balance of Balance of Efficacy and SafetyEfficacy and Safety

CV Death / MI / Stroke

TIMI Major NonCABG Bleeds

NNT = 46

NNH = 167Adapted with permission from Wiviott SD et al NEJM 357:2007

TRITON: Results

104

B

OVERALL

No GPIGPI

DESBMS

DMNo DM

>7565-74

<65

FemaleMale

STEMIUA/NSTEMI

0.5 1 2Prasugrel Better Clopidogrel Better

HR

Age

Reduction in risk (%)18

2112

25146

1430

2018

2116

19

21

Pinter = NS

CV Death, MI, StrokeCV Death, MI, StrokeMajor SubgroupsMajor Subgroups

CrCl > 60CrCl < 60 14

20

Wiviott SD et al NEJM 357: 2001, 2007

TRITON TIMI-38

105

0

2

4

6

8

0 1 2 3

1

0

3060 90 180 270 360 450

HR 0.82P=0.01

HR 0.80P=0.003

5.6

4.7

6.9

5.6

Days

Pri

ma

ry E

nd

po

int

(%)

Prasugrel

Clopidogrel

Prasugrel

Clopidogrel

Loading Dose Maintenance Dose

Timing of BenefitTiming of Benefit(Landmark Analysis - 3 days)(Landmark Analysis - 3 days)

Adapted with permission from Antman EM JACC 2008.

TRITON TIMI-38

106

Diabetic SubgroupDiabetic Subgroup

0

2

4

6

8

10

12

14

16

18

0 30 60 90 180 270 360 450

HR 0.70P<0.001

Days

En

dp

oin

t (%

) CV Death / MI / Stroke


NNT = 21

N=3146N=3146

17.0

12.2

Prasugrel

Clopidogrel

Prasugrel

Clopidogrel 2.6

2.5

Wiviott SD et al Circulation 2008.Adapted with permission from Antman EM.

TRITON TIMI-38

107

0

5

10

15

0 30 60 90 180 270 360 450

Per

cen

t (%

)

Days From Randomization

9.5%

6.5%

HR 0.68(0.54-0.87)

P=0.002

12.4%

10.0%

HR 0.79(0.65-0.97)

P=0.02

Clopidogrel

Prasugrel

NNT = 42

CV Death / MI / Stroke


Clopidogrel

Prasugrel 2.4

2.1

STEMI CohortSTEMI CohortN=3534N=3534

Montalescot et al Lancet 2008.Adapted with permission from Antman EM.

TRITON TIMI-38

108

Stent ThrombosisStent Thrombosis(ARC Definite + Probable)(ARC Definite + Probable)

0

1

2

3

0 30 60 90 180 270 360 450

HR 0.48P <0.0001

Prasugrel

Clopidogrel2.4

(142)

NNT= 77

1.1 (68)

Days

En

dp

oin

t (%

)

Any Stent at Index PCIAny Stent at Index PCI N= 12,844 N= 12,844

Adapted with permission from Wiviott SD et al Lancet 2008

Significant reductions both with BMS, DESSignificant reductions both with BMS, DESSignificant reductions in early and late stent thrombosesSignificant reductions in early and late stent thromboses

TRITON TIMI-38

109

1.8

0.9 0.9

0.10.3

2.4

1.41.1

0.4 0.3

0

2

4

TIMI MajorBleeds

LifeThreatening

Nonfatal Fatal ICH

% E

ven

ts%

Eve

nts

ARD 0.6%ARD 0.6%HR 1.32HR 1.32P=0.03P=0.03

NNH=167 NNH=167

ClopidogrelClopidogrel

PrasugrelPrasugrel

ARD 0.5%ARD 0.5%HR 1.52HR 1.52P=0.01P=0.01

ARD 0.2%ARD 0.2%P=0.23P=0.23

ARD 0%ARD 0%P=0.74P=0.74

ARD 0.3%ARD 0.3%P=0.002P=0.002

ICH in Pts w ICH in Pts w Prior Stroke/TIA Prior Stroke/TIA

(N=518)(N=518)

Clop 0 (0) %Clop 0 (0) % Pras 6 (2.3)%Pras 6 (2.3)% (P=0.02) (P=0.02)

Wiviott SD et al NEJM 357: 2001, 2007. Adapted with permission from Antman EM.

TRITON TIMI-38: Bleeding Events Safety Cohort (N=13,457)

110


For STEMI patients undergoing non-primary PCI, the

following regimens are recommended:

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII a. …and has been given clopidogrel, it should be continued as the thienopyridine of choice.

b. …without a thienopyridine, a loading dose of 300-600‡ mg of clopidogrel should be given as the thienopyridine of choice.

If the patient did not receive fibrinolytic therapy…c. …either a loading dose of 300-600 mg of clopidogrel

should be given or, once the coronary anatomy is known and PCI is planned, a loading dose of 60 mg of prasugrel should be given promptly and no later than 1 hour after the PCI.


If the patient has received fibrinolytic therapy…

MODIFIED

Rec

111

The duration of Thienopyridine therapy

112

Thienopyridines

The duration of thienopyridine therapy

should be as follows: MODIFIED

Recommendation


III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII a. In patients receiving a stent (BMS or DES) during PCI for ACS, clopidogrel 75 mg daily† or prasugrel 10 mg§ daily should be givenfor at least 12 months;

b. If the risk of morbidity from bleeding outweighs the anticipated benefit affordedby thienopyridine therapy, earlier discontinuation should be considered.

113

Thienopyridines


In patients taking a thienopyridine in whom coronaryartery bypass surgery (CABG) is planned and can be delayed, it is recommended that the drug be discontinuedto allow for dissipation of the antiplatelet effect.

The period of withdrawal should be at least 5 days inpatients receiving clopidogrel

and at least 7 days in patients receiving prasugrel,

… unless the need for revascularization and/or the netbenefit of the thienopyridine outweighs the potential risksof excess bleeding.

MODIFIED

Recommendation (prasugrel added)




114

Thienopyridines


Continuation of clopidogrel orprasugrel beyond 15 months

maybe considered in patientsundergoing drug-eluting stentplacement


115

Thienopyridines

NEW Recommendation

In STEMI patients with a priorhistory of stroke and

transientischemic attack for whom

primaryPCI is planned, prasugrel is

notrecommended as part of a

dualantiplatelet therapy regimen


116

Recommendations for

Use of Parenteral Anticoagulants in Patients

with STEMI

117

• Bilvalirudin added as an acceptable anticoagulant for primary PCI

• Unfractionated heparin (UFH) administration guided by:– Therapeutic activated clotting time (ACT) levels – Prior administration of GP IIb/IIIa receptor

antagonists• Enoxaparin and fondaparinux unchanged from 2007

STEMI Focused Update

Use of Parenteral Anticoagulants in STEMI Patients Proceeding to Primary PCI: Modified Class I Recommendations

118

HORIZONS-AMI: Design

Stone et al. N Eng J Med. 2008;358:2218-30.

3602 patients with STEMI & symptom onset ≤ 12 hours

randomized

1800 received bivalirudin alone*1802 received heparin +

GP IIb/IIIa inhibitor

Principal management strategyPrimary PCI, 1678 (93.2%)

Deferred PCI, 5 (0.3%)CABG, 23 (1.3%)

Medical management, 94 (5.2%)

Principal Management Strategy Primary PCI, 1662 (92.2%)

Deferred PCI, 3 (0.2%)CABG, 40 (2.2%)

Medical Management, 97 (5.4%)

Emergency angiography Emergency angiography

Endpoints: Composite of net adverse clinical events (NACE)

Included major bleeding plus MACE (a composite of CVD death, reinfarction, target-

vessel revascularization for ischemia, and stroke within 30 days)•

119

HORIZONS-AMI: Time-to-Event Curves through 30 days: Net Adverse Clinical Events

Treatment with bivalirudin alone compared with UFH + GP IIb/IIIa Inhibitors resulted in reduced 30-day rates of net adverse clinical events

[HR=0.75, (0.62-0.92); p=0.006]Stone et al. N Eng J Med. 2008;358:2218-30.

120

HORIZONS-AMI: Time-to-Event Curves through 30 days: Major Bleeding

HR=0.59 (0.45-0.76); p<0.0001* 40% less bleeding in Bivalirudin group at 30 days

Stone et al. N Eng J Med. 2008;358:2218-30.

121

CARESS-IN-AMI: Design

Di Mario et al. Lancet 2008;371.

• 600 STEMI pts <75 years old with > 1 high risk feature initially treated at non-PCI hospitals with half-dose reteplase, abciximab, heparin, and ASA within 12 hours of symptom onset

• All pts randomized to immediate transfer for PCI or to standard treatment with transfer for rescue PCI if needed

122

CARESS-IN-AMI: Study Flow Chart

600 STEMIASA 300-500 mg IVReteplase 5 U+5 U at 30 minUFH 40 u/kg (max 3000 per u) →7 u/kg/hAbciximab 0.25 mg/kg bolus →0.125 μg/kg/min for 12 h to a maximum 10 μg/min

299 assigned to immediate PCI1 consent not valid297 received reteplase289 transferred for immediate PCI255 received PCI

301 assigned to standard care/rescue PCI1 consent withdrawn298 received reteplase107 transferred for rescue PCI91 received PCI


123

CARESS-IN-AMI: Primary Outcomeprimary outcome (composite of all cause mortality, reinfarction, & refractory MI within 30 days) occurred significantly less often in the immediate PCI group vs. standard care/rescue PCI group

10.7%

4.4%

HR=0.40 (0.21-0.76)


124

TRANSFER-AMI

Study of pharmacoinvasive strategy in 1059 patients with STEMI presenting to non-PCI-capable hospitals within 12 hrs of symptom onset & with ≥ 1 high-risk feature

Cantor et al. N Eng J Med 2009;360:26.

125

TRANSFER-AMI: ResultsProcedures

Pharmaco-invasive vs. Standard Treatment

Median time to TNK administration from symptom onset

Approximately 2 hrs in both groups

Median time from TNK to catheterization

2.8 hrs vs. 32.5 hrs

Coronary angiography

98.5% vs. 88.7%

PCI performed 84.9% vs. 67.4%

Cantor et al. N Engl J Med 2009;360:26.

127

TRANSFER-AMIStudy Conclusion

• Following treatment with fibrinolytic therapy in high risk STEMI pts presenting to hospitals without PCI-capability, transfer to a PCI center to undergo coronary angiography and PCI should be initiated immediately without waiting to determine whether reperfusion has occurred.

Cantor et al. N Eng J M 2009;360:26.

128

Recommendations for Intensive Glucose Control

in STEMI

129

Intensive Glucose Control in STEMI

NEW Recommendation

It is reasonable to use an insulin

based regimen to achieve and

maintain glucose levels less than

180 mg/dl while avoidinghypoglycemia for patients

withSTEMI with either a

complicated oruncomplicated course


130

Recommendations for Thrombus Aspiration during PCI for STEMI

131

Thrombus Aspiration During PCI for STEMI

NEW Recommendation

Aspiration thrombectomy is

reasonable for patientsundergoing primary

PCI


132

Recommendations for the use of stents in

STEMI

133

Use of stents in STEMI

NEW Recommendation

It is reasonable to use a drug-

eluting stent as an alternative to a

bare-metal stent for primary PCI in

STEMI


* Consideration for the use of stents (DES or BMS) in STEMI should include the ability of the patient to comply with prolonged dual antiplatelet therapy, the bleeding risk in patients on chronic oral anticoagulation, and the possibility that the patient may need surgery during the ensuing year

134

Use of stents in STEMI


A DES may be considered forclinical and anatomic

settings† inwhich the efficacy/safety

profileappears favorable


135

Recommendations for the timing of Angiography and

Antiplatelet Therapy in UA/NSTEMI

136

Recommendations for the Timing of Angiography and Antiplatelet Therapy in UA/NSTEMI

NEW Recommendation



Patients with definite or likely UA/NSTEMI selected for an invasive approach should receive dual-antiplatelet therapy. Aspirin should be initiated on presentation. Clopidogrel (before or at the time of PCI) (Level of Evidence: A)

or

prasugrel (at the time of PCI) (Level of Evidence: B) is recommended as a second antiplatelet agent.

137

Recommendations for the Timing of Angiography and Antiplatelet Therapy in UA/NSTEMI


NEW Recommendation

It is reasonable for initially stabilized high-riskhigh-risk patients with UA/NSTEMI* (GRACE [Global Registry of Acute Coronary Events] risk score > 140) to undergo an early invasive strategy within 12 to 24 hours of admission. For patients not at high risknot at high risk, an early invasive approach is also reasonable.

138

TIMACS: Study design

Mehta et al. N Engl J Med. 2009;360:2165-75

Treatment

Routine early intervention (coronary angiography within 24 hours) or delayed

(coronary angiography at 36 hours+)

InclusionNSTE-ACS (no ST elevation within 24 hours of symptom onset) & high risk

Exclusion Not suitable for revascularization

1° OUTCOMES

Death, MI, stroke at 6 mo.

2 ° OUTCOMES

Refractory ischemia

139

TIMACS: Results


HR= 0.85 (95% CI, 0.68-1.06)

P=0.15

Early intervention significantly improvedoutcomes in highest risk patients

No significant difference in rate of death, new MI or stroke at 6 mo.

140

TIMACS: Results


Secondary Outcome: Early-intervention group had a 28% reduction in death, MI, or refractory ischemia compared to the delayed-intervention group.

HR, 0.72 (0.58-0.89)P=0.003

12.9%

9.5%

Secondary Prevention and Secondary Prevention and Long-Term ManagementLong-Term Management

AMI二级预防和长期治疗• 戒烟• 控制血压： B-B ACEI

• 降血脂： LDL≥100g% ，他汀 TG>150g or HDL<40g%,减体重、运动、戒烟 TG>200g% ，加贝特克 or烟酸 TG>500g% ，先贝特克 or烟酸，加鱼油

• STE-ACS （恢复期 PCI ）：时机最佳要考虑到病情，病变双稳定最重要冠造后高危病变的识别最关键！过早风险大，晚些才安全！• NSTE-ACS （ PCI ）药物治疗是基础危险分层最重要高危患者：优先 PCI or CABG 低危患者：优先药物冷却，稳定后 PCI or CABG 高中危患者：药物能控制，稳定后 PCI or CABG 不能控制者，紧急 PCI or

CABG

ACSACS治疗治疗 PCIPCI 策略要点策略要点(1)(1)

ACS治疗 PCI策略要点 (2)• 台上不同冠脉病变的处理原则

• 冠脉临界狭窄病变：药物稳定斑块治疗• 冠脉严重狭窄或次全闭塞 : PCI效果好• 冠脉多支病变（有 CTO ）：应先讨论

再 CABG 或 PCI• 冠脉血栓病变 : 血流好 : 2b/3a I 有特效 , No PCI

血流差： 2b/3a I ＋溶栓或

DVD+PCI• 冠脉复合病变 : 血流好 : 先药物 , 延迟 PCI ；

血流差： DVD(+IABP)+PCI, 准备无再流急救

领会 Guideline与临床实践之间的辩证关系

Guideline ：是理论，来源于实践。

虽能指导临床实践

但需经临床实践的检验

非一承不变，需通过实践来不

断补充、完善。

临床医疗：

是实践，需 Guideline指导。

又能检验 Guideline 的正确性，

实践出真知（理论），

坚持实践第一。

Guideline与临床实践紧密结合最关键• 避免只强调 Guideline ，不重视临床实践。

生搬硬套理论，不能解决临床实际问题，

则为教条主义。

• 避免忽视 Guideline 的指导，只强调个人经验。

没有 Guideline理论指导，“盲目”实践，

则为经验主义。

指南与实践的鸿沟

• 指南：– 太原则，太具体，太教条，难理解

• 实践：– 太个体，太多样，太灵活，难把握

• 两者间差距较大，甚至有“鸿沟”

• 唯有 CAP-CCBC 是解决这一问题的 “ 桥梁”或“有效途径”

医学专家的成功之道

正确领会 Guideline 的精神实质，指导自已的临床实践，并在实践中加以检验和提高，不断加深对

Guideline 的理解和增强在临床中应用的能力。如此往复循环，自已才能“获得”真知，驾轻就熟地解决复杂的临床问题。

唯有： CAP-CCBC 能使为每位有机会获得

成功，特邀请参加！

Thank you very much !

Welcome Attend China Heart Conference (IHF2010) ：

2nd international TR Coronary Therapeutics (TRCT)

Chaired byYue-Jin Yang MD. PhD. FACC

Co-Chaired byDr. Saito

Dr. kiemeneijiNCC, 2010/08/12-15, Beijing, China

Thank youThank you

Documents

STEMI: Guidelines Udate 2009 and Clinical Practice