1. ACS and Thrombosis in the Emergency Setting
STEMI

2. 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 PCI b) Immediate fibrinolysis and then transfer to cardiac centre c) Immediate fibrinolysis with transfer only if no reperfusion

3. Choosing the Optimal Reperfusion Strategy
Goal is rapid reperfusion
Time targets from first medical contact to treatment
Fibrinolysis 30 minutes
Primary angioplasty (PPCI) minutes
Delayed reperfusion associated with increased mortality
When time to PPCI will exceed 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

4. Impact of Delay to Primary PCI
90 DAY MORTALITY RELATED TO DOOR-TO-BALLOON TIME
(n=1071)
(n=1354)
(n=1186)
(n=1762)
<60 min
60-90 min
min
≥120 min
SURVIVAL (%)
99%
98%
97%
96%
95%
94%
93%
92%
100%
3.2%
90-day mortality
4.0%
4.6%
5.3%
P<0.0001 10 20 30 40 50 60 70 80 90
DAYS
Hudson MP et al. Circ Cardiovasc Qual Outcomes 2011;4:183-92

5. Which Patients Cannot Afford a PPCI Delay?
PCI RELATED DELAY (DB-DN) WHERE PCI AND FIBRINOLYTIC MORTALITY ARE EQUAL (MIN)
NonAnt MI 65+ YRS
180
120 60
Ant MI 65+ YRS
NonAnt MI < 65 YRS
Ant MI < 65 YRS
0-120 Prehospital Delay (min)
121+ 40 43 58
103
107
148
168
179
20,424
10,614
9,812
3,739
41,774
16,119
19,517
5,296
Pinto DS et al. Circulation 2006; 114:

6. Prehospital and In-Hospital Management and Reperfusion Strategies
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 diagnosisa
Primary-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
PCI possible ˂120 min?
Immediate
fibrinolysis
Successful fibrinolysis?
Immediate transfer to PCI center
Preferably ≤90 min
(≤60 min in early presenters)
Immediate transfer
to PCI center
Preferably
≤30 min
ESC STEMI Guidelines 2012

7. Q2: In the event that the patient receives fibrinolysis, which anticoagulant is preferred?
a) UHF
b) Enoxaparin
c) Fondaparinux
Q3: Which would be the optimal antiplatelet agent to add to the anticoagulant?
a) clopidogrel
b) ticagrelor
c) prasugrel

8. Anticoagulation and Antiplatelet Therapy with Fibrinolysis
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 mg 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
4.2. Adjunctive Antithrombotic Therapy
With Fibrinolysis
See Table 5 for a summary of recommendations from this
section.
Adjunctive Antiplatelet Therapy With Fibrinolysis
Class I
1. Aspirin (162- to 325-mg loading dose) and clopidogrel
(300-mg loading dose for patients <75 years
of age, 75-mg dose for patients >75 years of age)
should be administered to patients with STEMI who
receive fibrinolytic therapy.113,121,122 (Level of Evidence: A)
2. Aspirin should be continued indefinitely113,121,122
(Level of Evidence: A) and clopidogrel (75 mg daily)
should be continued for at least 14 days121,122 (Level
of Evidence: A) and up to 1 year (Level of Evidence:
C) in patients with STEMI who receive fibrinolytic
therapy.
Class IIa
1. It is reasonable to use aspirin 81 mg per day in
preference to higher maintenance doses after fibrinolytic
therapy.77,80,86,87 (Level of Evidence: B)
Adjunctive Anticoagulant Therapy
1. Patients with STEMI undergoing reperfusion with
fibrinolytic therapy should receive anticoagulant
therapy for a minimum of 48 hours, and preferably
for the duration of the index hospitalization, up to 8
days or until revascularization if performed.123,124
(Level of Evidence: A) Recommended regimens
include
a. UFH administered as a weight-adjusted intravenous
bolus and infusion to obtain an activated
partial thromboplastin time of 1.5 to 2.0 times
control, for 48 hours or until revascularization
(Level of Evidence: C);
b. Enoxaparin administered according to age,
weight, and creatinine clearance, given as an
intravenous bolus, followed in 15 minutes by
subcutaneous injection for the duration of the
index hospitalization, up to 8 days or until revascularization124–
127 (Level of Evidence: A); or
c. Fondaparinux administered with initial intravenous
dose, followed in 24 hours by daily
subcutaneous injections if the estimated creatinine
clearance is greater than 30 mL/min, for
the duration of the index hospitalization, up to
8 days or until revascularization.110 (Level of
Evidence: B)
2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction

9. 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
Transfer to a PCI-capable hospital for coronary
angiography is reasonable for patients with
STEMI who have received fibrinolytic therapy
even when hemodynamically stable§ and with
clinical evidence of successful reperfusion. Angiography
can be performed as soon as logistically
feasible at the receiving hospital, and ideally
within 24 hours, but should not be performed
within the first 2 to 3 hours after administration of
fibrinolytic therapy.133–138 (Level of Evidence: B)
2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction

10. Impact of Routine Early Transfer for PCI after Fibrinolysis
DEATH, REINFARCTION, WORSENING HEART FAILURE, OR CARDIOGENIC SHOCK
0.20
0.15
0.10
0.00
0.05 5 30
DAYS 10 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,
Early PCI hrs
Standard treatment PCI hrs
Cantor et al N Eng J Med 2009;360:2705

11. 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

12. Oral Antiplatelets in STEMI
TRITON TIMI 38 Prasugrel vs Clopidogrel CV death / MI / Stroke
CUMULATIVE INCIDENCE (%)
DAYS FROM RANDOMISATION
HR % CI p=0.0221 15 10 5 50
300
100
150
200
250
350
400
450
Clopidogrel
Prasugrel
P=0.0017
P=0.0221
PLATO Ticagrelor vs Clopidogrel CV death / MI / Stroke
Clopidogrel
Ticagrelor
CUMULATIVE INCIDENCE (%) 1 2 3 4 5 6 7 8 9 10 11 12
MONTHS
HR 0.87; 95% CI ; P= 0.07
At risk
60% Primary PCI 30% Secondary delayed PCI
No reduction of mortality, MI HR 0.70 p=0.01
Stent thrombosis HR 0.58 p=0.23
No increase in TIMI major or life threatening bleeding
All primary PCI
Mortality HR, 0.82; P= MI HR 0.80 p=0.03
Stent thrombosis HR 0.60 p=0.03
Stroke increased 1.7% vs 1.0% HR 1.63 p=0.02
No increase in major bleeding
Montelescot et al Lancet 2009; 373: 723
Steg et al Circulation. 2010;122:2131

13. DEATH, SHOCK, CHF, OR REINFARCTION
Pre-Hospital Fibrinolysis + PCI vs Primary PCI for Patients Unable to Undergo Primary PCI within 1 Hour
RR 0.86; 95% CI, ; P = 0.21
DEATH, SHOCK, CHF, OR REINFARCTION % 20 15 10 5 30
DAYS 25
Primary PCI
Fibrinolysis
STREAM Study Armstrong et al N Eng J Med 2013;368:1379

14. 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 fibrinolysis b) Transfer to regional cardiac centre for PCI c) Manage medically with UFH and ASA

15. 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 < 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 Summary

16. 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 mg loading and 81mg maintenance; UHF, bivalirudin with or without prior UHF)
O’Gara et al 2013 ACCF/AHA STEMI Guideline Executive Summary

17. candidate for reperfusion
2013 STEMI Management
STEMI patient who is a
candidate for reperfusion
Initially seen at a PCI-capable
hospital
Initially seen at a
non-PCI-capable
Hospital*
Send to cath lab for primary PCI FMC-device time ≤90 min
(Class 1, LOE: A)
Diagnostic angiogram
PCI
CABG
Medical
therapy only
DIDO time≤30 min
Transfer for primary PCI
FMC-device time as soon as Possible and
≤120 min
(Class 1, LOE: B)
Administer fibrinolytic
agent within 30 min of arrival when anticipated FMC- device >120 min
Transfer for angiography and revascularization
within 3-24 h for other patients as part of an invasive strategyϮ
(Class IIa, LOE: B)
Urgent transfer for
PCI for patients
with evidence of
failed reperfusion
or reocclusion
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.
O’Gara et al 2013 ACCF/AHA STEMI Guideline Executive Summary