超过再灌注治疗时间窗的 STEMI 患者的介入治疗策略选择...

超过再灌注治疗时间窗的STEMI 患者的介入治疗策略选

择

浙江大学医学院附属第一医院朱建华

2011.11.20 2011ACS 研讨会北京亮马河大厦

Circulation. 2003;108:III-14-III-21

Data from TETAMI Study

＞ 12 小时 STEMI 的特点

以高龄患者为多；

多合并其它疾病（糖尿病、高血压、慢性肾病、脑血管疾病、肿瘤等）；

更倾向于保守治疗；

当地医疗条件相对不足，依从性差；

Circulation. 1977;56: 786-794

40min

3 hours

24 hours

96 hours

Time Is Muscle, Muscle Is Life

JAMA. 2005;293(8):979-986

OAT 试验 : 研究设计

一级终点 : 死亡，心梗，或 NYHA IV 心衰一级终点 : 死亡，心梗，或 NYHA IV 心衰

PCIn=1082

PCIn=1082

药物治疗n=1084

药物治疗n=1084

2166 patients with angiography on day 3-28 post-MI with evidence of total occlusion of the infarct-related artery with poor or absent antegrade flow (TIMI flow grade 0 or

1); and met a criterion for increased risk, defined as ejection fraction <50%, proximal occlusion of a major epicardial vessel with a large risk region, or both

Exclusions: NYHA class III or IV heart failure, shock , serum creatinine concentration >2.5 mg/dl, angiographically significant left main or three-vessel coronary artery disease, angina at rest, or severe ischemia on stress testing.

Randomized.22% female, mean age 59 years, mean follow-up 3 years, mean EF 48% at baseline

Concomitant medications: Aspirin, anticoagulation if indicated, ACE inhibitors, beta-blockers, and lipid-lowering therapy, unless contraindicated

2166 patients with angiography on day 3-28 post-MI with evidence of total occlusion of the infarct-related artery with poor or absent antegrade flow (TIMI flow grade 0 or

1); and met a criterion for increased risk, defined as ejection fraction <50%, proximal occlusion of a major epicardial vessel with a large risk region, or both

Exclusions: NYHA class III or IV heart failure, shock , serum creatinine concentration >2.5 mg/dl, angiographically significant left main or three-vessel coronary artery disease, angina at rest, or severe ischemia on stress testing.

Randomized.22% female, mean age 59 years, mean follow-up 3 years, mean EF 48% at baseline

Concomitant medications: Aspirin, anticoagulation if indicated, ACE inhibitors, beta-blockers, and lipid-lowering therapy, unless contraindicated

N Engl J Med 2006;355:2395–2407.N Engl J Med 2006;355:2395–2407.

OAT 试验 : 一级终点


Primary Endpoint of death, reinfarction, NYHA class IV heart failure (% patients)

Hazard Ratio 1.16, p=0.20

OAT Trial: Primary Component Endpoints


Primary Component Endpoints (% patients)

TotalReinfarction

% p

atie

nts

NonfatalReinfarction

DeathRepeated ↑ of Cardiac

Biomarkers

NYHA Class IV Heart Failure

p=0.13p=0.13 p=0.08p=0.08

p<0.001p<0.001p=0.83p=0.83

p=0.92p=0.92

OAT 试验 : 小结


对心肌梗死后 3-28 天梗死相关血管全闭的稳定的高危病人行 PCI 治疗与药物治疗相比， 3 年随访发现，死亡，再梗或心衰复合终点无显著差异。

尽管复合终点无差异，但是， PCI 与药物治疗相比再梗的发生率有增加的趋势。

对 PCI 再梗率有增加的趋势的一个解释是，可能是栓塞造成心肌损害和损害了侧枝血流所致。

＞ 12 小时 STEMI 的指南建议临床表现 ESC 2008 ACC/AHA/SCAI 2009

＞ 12 小时就诊，同时伴有：

再发心梗 N/A急诊 PCI (Class I,

LOE: C)

心源性休克 or 血流动力学不稳定急症 PCI (Class I, LOE: C)

急诊 PCI (Class I, LOE: B)

恶性心律失常 or 心衰 N/A急诊 PCI (Class IIa,

LOE: C)

＞ 12 小时就诊，同时伴有持续性心绞痛急诊 PCI (Class IIa, LOE: C)

急诊 PCI (Class I, LOE: B)

12-24 小时就诊，无症状急诊 PCI (Class IIb, LOE: B)

N/A

＞ 24 小时就诊，无症状不推荐急诊 PCI(Class III, LOE: B)

不推荐急诊 PCI(Class III, LOE: B)

对于 12-24 小时无症状STEMI 患者是否要行急诊

PCI 存在争议将 12 小时作为分界点过于武断（主要来源于溶栓

时代的研究）， PCI 相较于溶栓有许多不同点；血栓抽吸装置的出现为 PCI 治疗提供了更多优势；自然状态的 AMI 不同于动物实验的单纯阻断血管

（残余前向血流、缺血预适应、侧支循环等机制可能保留了更多的存活心肌）；

即使无缺血症状也不能说明一定不存在存活心肌；

BRAVE-2 试验 : 研究设计

一级终点 : Final left ventricular infarct size according SPECT with Tc 99m sestamibi performed between 5 and 10 days after randomization

二级终点： Composite of death, recurrent MI, or stroke at 30 days.

一级终点 : Final left ventricular infarct size according SPECT with Tc 99m sestamibi performed between 5 and 10 days after randomization

二级终点： Composite of death, recurrent MI, or stroke at 30 days.

介入治疗组n=182

介入治疗组n=182

保守治疗组n=183

保守治疗组n=183

目标 : To assess whether an immediate invasive treatment strategy is associated with a reduction of infarct size in patients with acute STEMI, presenting between 12 and 48 hours after symptom onset, vs a conventional conservative strategy.

设计 : International, multicenter, open-label, randomized controlled trial conducted from May 23, 2001, to December 15, 2004. 365 patients aged 18 to 80 years without persistent symptoms admitted with the diagnosis of acute STEMI between 12 and 48 hours after symptom onset were randomized.

目标 : To assess whether an immediate invasive treatment strategy is associated with a reduction of infarct size in patients with acute STEMI, presenting between 12 and 48 hours after symptom onset, vs a conventional conservative strategy.

设计 : International, multicenter, open-label, randomized controlled trial conducted from May 23, 2001, to December 15, 2004. 365 patients aged 18 to 80 years without persistent symptoms admitted with the diagnosis of acute STEMI between 12 and 48 hours after symptom onset were randomized.

JAMA. 2005;293:2865-2872.JAMA. 2005;293:2865-2872.

BRAVE-2 试验 : 一级终点

JAMA. 2005;293:2865-2872.JAMA. 2005;293:2865-2872.

BRAVE-2 试验 : 二级终点

JAMA. 2005;293:2865-2872.JAMA. 2005;293:2865-2872.

BRAVE-2 试验 : 总结

对于心梗 12-48 小时的无症状患者，急诊 PCI 手术相较于药物保守治疗能明显减少梗死心肌范围；

在 30 天临床终点事件方面（死亡、再发心梗、卒中），急诊 PCI 手术与药物保守治疗相比无差别；

造影发现，这些患者中 TIMI 0 血流仅占 27% ，其余 73% 存在前向血流或侧支循环。

JAMA. 2005;293:2865-2872.JAMA. 2005;293:2865-2872.

Danish 研究

Myocardial perfusion imaging (MPI) was performed acutely to assess area at risk (AAR) before angioplasty and repeated after 30 days to assess FIS (% of LV

myocardium), salvage index (% non-infarcted AAR), and left ventricular ejection fraction (LVEF).

Myocardial perfusion imaging (MPI) was performed acutely to assess area at risk (AAR) before angioplasty and repeated after 30 days to assess FIS (% of LV

myocardium), salvage index (% non-infarcted AAR), and left ventricular ejection fraction (LVEF).

Early presenters(n = 341)

PCI < 12 hoursafter symptom onset

Early presenters(n = 341)

PCI < 12 hoursafter symptom onset

late presenters(n = 55)

PCI between 12 and 72 hoursafter symptom onset

late presenters(n = 55)

PCI between 12 and 72 hoursafter symptom onset

396 例 STEMI 病人396 例 STEMI 病人

European Heart Journal (2009) 30, 1322–1330European Heart Journal (2009) 30, 1322–1330

Danish StudyDanish Study

European Heart Journal (2009) 30, 1322–1330European Heart Journal (2009) 30, 1322–1330

Early(N = 341)

Late(N =55)

P Value

AAR (%) 28 (18-40) 31 (22-45) 0.04

Salvage Index (%) 69 (45-91) 53 (27-89) 0.05

LVEF (%) 52 (47-59) 48 (44-58) 0.04

LVEDV (ml) 115 (92-138) 121 (99-146) 0.27

LVESV (ml) 53 (39-70) 57 (45-80) 0.10

1-year Mortality 0.9 3.6 0.05

Eur Heart J 2006; 27: 1900–1907

Primary PCI is recommended for the

treatment of STEMI in patients presenting

with symptoms for less than 12 hoursAntman EM et al., AHA/ACC STEMI guidelines 2007:

Circulation 2008;117:296-329.

Background

Primary PCI is recommended for the treatment of STEMI in patients

presenting with symptoms for less than 12 hoursAntman EM et al., AHA/ACC STEMI guidelines 2007:

Circulation 2008;117:296-329.

However, 8.5-40% of STEMI-patients are ”late presenters” with

symptoms for more than 12 hours on admission

Schomig A et al., Eur Heart J 2006;27:1900-1907

Background

BRAVE-2 is the only trial on primary

angioplasty vs. medical therapy in STEMI-

patients with symptoms for 12-48 hours on

admissionSchomig A et al., JAMA 2005;293:2865-2872

Parodi G et al., Am Heart J 2006;152:1133-1139

Background

BRAVE-2 is the only trial on primary angioplasty vs. medical

therapy in STEMI-patients with symptoms for 12-48 hours on



Final infarct size:

Primary PCI vs. Medical therapy: p<0.001

Background

8% 13%

BRAVE-2 is the only trial on primary angioplasty vs. medical

therapy in STEMI-patients with symptoms for 12-48 hours on



Salvage index (% of risk area salvaged):

Primary PCI vs. Medical therapy: p<0.001

Background

44% 23%

To evaluate if the 12-hour limit is a relevant cut-off point for offering primary angioplasty

Aim

Late presenters (12-72 h) do not achieve

myocardial salvage after primary

angioplasty and therefore develop larger

final infarct sizes than early presenters

(<12 h)

Hypothesis

Symptom duration was defined as time from

onset of symptoms to first balloon inflation

= pain-to-balloon interval

Definition of symptom duration

Myocardial scintigraphybefore primary PCI:

Myocardial scintigraphy30 days later:

Salvage = 46-5 = 41% of LV myocardium

Salvage index = 41/46 = 89% of area at risk

Area at risk = 46% Infarct size = 5%

Method: Myocardial scintigraphy

1) Ndrepepa G, J Nucl Med 2004; 45:725-729; 2) Burns RJ, JACC 2002;39:30-6

Primary outcome: Infarct size (% of LV)

Power calculation*:

<12 h: Infarct size = 15±10%: n=200

12-72 h: Infarct size = 20±10%: n=60

(Clinicaltrials.gov, study no. NTC00260416)

*2α=0.05, β=0.20 (power=0.80)

Study design

From May 1, 2005 to April 26, 2007 we used a

uniform treatment protocol for all STEMI-patients

presenting between 30 minutes and 72 hours after

onset of symptoms:

Aspirin, clopidogrel, heparin, immediate transfer to the

cath.lab., primary angioplasty with stent implantation,

and infusion of abciximab

Study design

Pain-to-balloon interval < 72 hours

Immediate transfer for PCI (not sub-acute)

Cumulated ST-elevation > 2 mV (ECG-12)or

New Q-waves & TnT > 0.1 μg/l

Inclusion criteria

PCI within previous 30 days

Previous CABG

Left main stenosis

Peak troponin T < 0.1 μg/l

Risk area < 5% of LV

Re-infarction, re-PCI or CABG during follow-up

Thrombectomy

Exclusion criteria

Consent, n=619

Inclusion, n=415

Exclusion, n=204• By criteria, n=152• No final scintigraphy, n=52 (6 deaths)

<12 hours, n=360 12-72 hours, n=55

Patient inclusion

<12 h (n=360) 12-72 h (n=55) p

Women (%) 25 33 0.24

Age (y) 62±12 63±10 0.84

Diabetes (%) 9 4 0.18

Hypertension (%) 32 31 0.84

Hypercholesterolaemia (%) 19 9 0.19

Previous AMI (%) 7 0 0.04 *

Median BMI (kg / m²) 26 (IQR 24-29) 26 (IQR 24-29) 0.67

Smoker (%) 56 50 0.39

Anterior STEMI (%) 43 55 0.11

Multi vessel disease (%) 41 49 0.23

Pre-PCI TIMI 0 (%) 60 56 0.76

Pre-PCI TIMI 1 (%) 6 9



Post-PCI TIMI 3 (%) 91 87 0.45

Filter wire protection (%) 36 5 <0.001 *

Abciximab (Reopro) (%) 96 98 0.44

Baseline characteristics

* No impact on primary endpoint

Primary outcome: Infarct size

Linear regression:p<0.001 R²=0.05

6 % 14 % p=0.002 (1-17) (3-30)

(n=415) Symptom duration (h)

Infa

rct

size

(%

of

LV)

Area at risk

25 % 31 % p=0.005 (15-39) (22-45)

Linear regression:p=0.008 R²=0.03

(n=262) Symptomvarighed (t)

Are

a at

ris

k (%

af

LV

)

Symptom duration (h)

Are

a a

t ri

sk (

% o

f LV

)

Salvage index

69 % 53 % p=0.06 (45-92) (27-89)


(n=262)

S

alva

ge

/ A

AR

(%

)

Symptomvarighed (t) Symptom duration (h)

Symptomvarighed (t)

Inf

arkt

-stø

rrel

se (

% a

f LV

)

Linear regression:

p<0.001 R²=0.07 11 % 20 % p=0.009(3-21) (7-35)


Total occlusion subgroup:Infarct size

Infa

rct

size

(%

of

LV)

Symptomvarighed (t)

Sa

lva

ge

/ AA

R (

%)

57 % 44 % p=0.03(42-86) (23-73)


Total occlusion subgroup:Salvage index


Time-to-treatment in primary PCI does matter: Infarct size increases and salvage index decreases (”time is muscle”) in the interval 0-72 hours

Conclusions


Substantial salvage is observed despite symptom durations of 12-72 hours, even when the infarct-related artery is totally occluded

Conclusions


Substantial salvage is observed despite symptom durations of 12-72 hours, even when the infarct-related artery is totally occluded

Latecomers should be considered for primary PCI

Conclusions

对乡村地区预期由于长距离转运而造成时间延误的 STEMI 病人采用药物 -介入治疗策略的

安全性和有效性研究

结论结论 :: For STEMI pts facing long delays to a PCI center, half-dose lytic therapy For STEMI pts facing long delays to a PCI center, half-dose lytic therapy plus immediate transfer for PCI is a safe alternative to primary PCI.plus immediate transfer for PCI is a safe alternative to primary PCI.

2,634 pts received either primary PCI or half-dose fibrinolytic plus immediate transfer for PCI, depending on distance from PCI center.

Larson DM, et al. Eur Heart J.2011;Epub ahead of print.

30-Day Outcomes30-Day OutcomesPrimary PCIPrimary PCI

(n = 1,763)(n = 1,763)

Pharmaco-Pharmaco-InvasiveInvasive(n = 692)(n = 692) P P ValueValue

MortalityMortality 5.6%5.6% 5.8%5.8% 0.870.87

Recurrent Ischemia/MIRecurrent Ischemia/MI 1.5%1.5% 1.3%1.3% 0.670.67

TIMI Major BleedingTIMI Major Bleeding 1.4%1.4% 1.6%1.6% 0.760.76

European Heart Journal (2010) 31, 2501–2555

从症状开始起 12-24 小时，甚至可能至 60 小时的病人，即使疼痛缓解，血流动力学稳定，也有可能从早期冠脉造影及可能的 PCI 中获益。

总结总结重视心梗后 12-72 小时就诊的患者，即使没有症状，

不说明没有存活心肌，急诊 PCI 治疗可能获益；

尽可能应用血栓抽吸、 IIb/IIIa拮抗剂等手段，减少无复流现象，挽救更多心肌；

如果由于转运造成时间延误，可以采用药物 -介入治疗策略以挽救心肌；

急诊 PCI队伍可能面临更大的压力；

Thank You!

超过再灌注治疗时间窗的 STEMI 患者的介入治疗策略选择...

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超过再灌注治疗时间窗的 STEMI 患者的介入治疗策略选 择...

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Transcript of 超过再灌注治疗时间窗的 STEMI 患者的介入治疗策略选 择...

超过再灌注治疗时间窗的 STEMI 患者的介入治疗策略选择...

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