STEMI

ACS and Thrombosis in the Emergency Setting

Q1: Which reperfusion strategy would you select as optimal for this patient if the nearest cardiac center were 3 hours drive away?

a) Immediate transfer to cardiac cath lab for primary PCIb) Immediate fibrinolysis and then transfer to cardiac centrec) Immediate fibrinolysis with transfer only if no reperfusion

Choosing the Optimal Reperfusion Strategy

Goal is rapid reperfusion Time targets from first medical contact to treatment

Fibrinolysis 30 minutes Primary angioplasty (PPCI) 90-120 minutes

Delayed reperfusion associated with increased mortality When time to PPCI will exceed 90-120 minutes fibrinolysis

should be given immediately Time delay for PPCI to achieve greater benefit than

fibrinolysis may be less than 90 minutes when Anterior MI Patient age <65 yrs Time from symptom onset <120 minutes

Impact of Delay to Primary PCI

90 DAY MORTALITY RELATED TO DOOR-TO-BALLOON TIME

Hudson MP et al. Hudson MP et al. Circ Cardiovasc Qual Outcomes 2011;4:183-92

SURVIVAL(%)

0 10 20 30 40 50 60 70 80 90

(n=1071)(n=1354)(n=1186)(n=1762)

<60 min60-90 min90-120 min≥120 min

99%

98%

97%

96%

95%

94%

93%

92%

100%

3.2%

90-day mortality

4.0%4.6%

5.3%

DAYS

P<0.0001

Which Patients Cannot Afford a PPCI Delay?

Pinto DS et al. Circulation 2006; 114: 2019-2025Pinto DS et al. Circulation 2006; 114: 2019-2025

PCI RELATED DELAY (DB-DN) WHERE PCI AND FIBRINOLYTIC

MORTALITY ARE EQUAL (MIN)

NonAnt MI65+ YRS

180

120

60

0Ant MI65+ YRS

NonAnt MI < 65 YRS

Ant MI < 65 YRS

0-120 Prehospital Delay (min)121+

40 43

58

103107

148

168179

20,424

10,614

9,812

3,739

41,774

16,119

19,517 5,296

Prehospital and In-Hospital Management and Reperfusion Strategies

ESC STEMI Guidelines 2012ESC STEMI Guidelines 2012

aThe time point the diagnosis is confirmed with patient history and ECG ideally within 10 min from the first medical contact (FMC). All delays are related to FMC (first medical contact).

Cath = catheterization laboratory; EMS = emergency medical system; FMC = first medical contact; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction

STEMI diagnosisaPrimary-PCI capable center

EMS or non primary-PCI capable center

Preferably ˂60 min

Primary-PCI

Rescue PCI

Coronary angiography

NO

YES

Immediately

Preferably 3-24 h

YES NO

PCI possible ˂120 min?

Immediate fibrinolysisSuccessful fibrinolysis?

Immediate transfer to PCI center

Preferably ≤90 min(≤60 min in early presenters)

Immediate transferto PCI center

Preferably≤30 min

Q2: In the event that the patient receives fibrinolysis, which anticoagulant is preferred?

a) UHFb) Enoxaparinc) Fondaparinux

Q3: Which would be the optimal antiplatelet agent to add to the anticoagulant?

a) clopidogrelb) ticagrelorc) prasugrel

Anticoagulation and Antiplatelet Therapy with Fibrinolysis

Anticoagulation Initiate UFH, enoxaparin or fondaparinux immediately after

administration of fibrinolytic agent• UFH 70u/kg iv• Enoxaparin

– <75yrs old 30mg iv bolus followed by s/c 1mg/kg– >75yrs old no iv bolus, s/c 1mg/kg

Fondaparinux 2.5mg s/c

Antiplatelet Therapy ASA 81-160mg po Clopidogrel

• <75 yrs old 300mg load followed by 75mg daily• > 75 yrs old no load, 75mg po daily

NB Ticagrelor and Prasugrel should not be used with fibrinolysis as they have not been tested in this situation

2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction

Need for PCI after Fibrinolysis

Rescue PCI Failed fibrinolysis

• Persistence of chest pain• Failure of ST elevation to decrease more than 50% at 1 hr

after fibrinolysis

Pharmaco-Invasive strategy Consider routine transfer patients to cardiac centre for PCI

within 2-24 hrs of fibrinolysis

2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction

Impact of Routine Early Transfer for PCI after Fibrinolysis

Cantor et al N Eng J Med 2009;360:2705Cantor et al N Eng J Med 2009;360:2705

DEATH, REINFARCTION, WORSENING HEART FAILURE, OR CARDIOGENIC SHOCK

0.20

0.15

0.10

0.00

0.05

0 5 30 DAYS10 15 20 25

Standard treatment

Routine early PCI

Death, reinfarction, or recurrent ischemia HR 0.65 (95% CI 0.44–0.96)

HR 0.64; 95% CI, 0.47 - 0.87

Early PCI 2.8 hrsStandard treatment PCI 32.5 hrs

Primary PCI for STEMI

Improved outcomes if PPCI performed in timely manner

Delayed PPCI worse than timely fibrinolysis

Goal Patient contact to PCI < 90 minutes for most patients

Adjuvant anticoagulation / antiplatelet agents By agreement with local interventional cardiology team

Oral Antiplatelets in STEMI

All primary PCI

Mortality HR, 0.82; P=0.05 MI HR 0.80 p=0.03Stent thrombosis HR 0.60 p=0.03Stroke increased 1.7% vs 1.0% HR 1.63 p=0.02 No increase in major bleeding

60% Primary PCI 30% Secondary delayed PCI

No reduction of mortality, MI HR 0.70 p=0.01Stent thrombosis HR 0.58 p=0.23

No increase in TIMI major or life threatening bleeding

Montelescot et al Montelescot et al LancetLancet 2009; 373: 723 2009; 373: 723 Steg et al Circulation. 2010;122:2131Steg et al Circulation. 2010;122:2131

TRITON TIMI 38 Prasugrel vs ClopidogrelCV death / MI / Stroke

CUMULATIVE INCIDENCE (%)

DAYS FROM RANDOMISATION

HR 0.79 95% CI 0.65-0.97 p=0.0221

15

10

5

00 50 300100 150 200 250 350 400 450

Clopidogrel

Prasugrel

P=0.0017 P=0.0221

At risk

PLATO Ticagrelor vs ClopidogrelCV death / MI / Stroke

Clopidogrel

Ticagrelor

CUMULATIVE INCIDENCE (%)

0123456789

101112

MONTHS0 1 2 3 4 5 6 7 8 9 10 11 12

HR 0.87; 95% CI 0.75 - 1.01; P= 0.07

Pre-Hospital Fibrinolysis + PCI vs Primary PCI for Patients Unable to Undergo Primary PCI within 1

Hour

STREAM Study Armstrong et al N Eng J Med 2013;368:1379 STREAM Study Armstrong et al N Eng J Med 2013;368:1379

RR 0.86; 95% CI, 0.68 -1.09; P = 0.21

DEATH, SHOCK, CHF, OR REINFARCTION

% 20

15

10

0

5

0 5 30 DAYS10 15 20 25

Primary PCI

Fibrinolysis

Q4: How would you have handled this patient if in addition to medical history described, he also had a recent (past 6 months) CVA?

a) Administer fibrinolysisb) Transfer to regional cardiac centre for PCIc) Manage medically with UFH and ASA

2013 STEMI Management

Early identification of STEMI- pre hospital preferred Performing 12-lead ECG by EMS personnel or at site of first

medical contact Early decision for reperfusion strategy and administration

within 12 hours of symptom onset for all eligible STEMI patients Primary PCI preferred if can be performed in timely manner

(First medical contact to PCI < 90 -120 min) Consider fibrinolysis in young anterior STEMI presenting

< 120 minutes from symptom onset if PCI not available within 60 minutes

O’Gara et al 2013 ACCF/AHA STEMI Guideline Executive SummaryO’Gara et al 2013 ACCF/AHA STEMI Guideline Executive Summary

2013 STEMI Management (cond’t)

Following fibrinolysis consider referral for early PCI

Choice of anticoagulant / antiplatelet agent depends upon reperfusion strategy and policy of PCI centre (P2Y12 receptor inhibitor therapy prior to PCI and maintenance for a year; ASA 160-325mg loading and 81mg maintenance; UHF, bivalirudin with or without prior UHF)

O’Gara et al 2013 ACCF/AHA STEMI Guideline Executive SummaryO’Gara et al 2013 ACCF/AHA STEMI Guideline Executive Summary

2013 STEMI Management

O’Gara et al 2013 ACCF/AHA STEMI Guideline Executive SummaryO’Gara et al 2013 ACCF/AHA STEMI Guideline Executive Summary

Figure 1. Reperfusion therapy for patients with STEMI. The bold arrows and boxes are the preferred strategies. Performance of PCI is dictated by an anatomically appropriate culprit stenosis. *Patients with cardiogenic shock or severe heart failure initially seen at a non-PCI-capable hospital should be transferred for cardiac catheterization and revascularization as soon as possible, irrespective of time delay from MI onset (Class I, LOE: B). Ϯangiography and revascularization should not be performed within the first 2 to 3 hours after administration of fibrinolytic therapy. CABG indicates coronary artery bypass graft; DiDO, door-in-door-out; FMC, first medical contact; LOE, Level of Evidence; MI, myocardial infarction; PCI, percutaneous coronary intervention; and STEMI, ST-elevation myocardial infarction.

STEMI patient who is a candidate for reperfusion

Initially seen ata PCI-capable

hospital

Initially seen at anon-PCI-capable

Hospital*

Send to cath lab for primary PCI FMC-device

time ≤90 min(Class 1, LOE: A)

Diagnostic angiogram

PCI CABGMedicaltherapy only

DIDOtime≤30 min

Transfer for primary PCIFMC-device time as soon

as Possible and ≤120 min

(Class 1, LOE: B)

Administer fibrinolyticagent within 30 min of

arrival when anticipated FMC- device >120 min

(Class 1, LOE: B)

Transfer for angiography and revascularization

within 3-24 h for other patients as part of an

invasive strategyϮ(Class IIa, LOE: B)

Urgent transfer forPCI for patients

with evidence offailed reperfusion

or reocclusion (Class IIa, LOE: B)