ACS and Thrombosis in the
Emergency Setting
STEMI
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
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
<60 min
60-90 min
90-120 min
≥120 min
SURVIVAL 100%
(%)
99%
(n=1071)
(n=1354)
(n=1186)
(n=1762)
98%
90-day
mortality
97%
3.2%
96%
4.0%
4.6%
95%
5.3%
94%
P<0.0001
93%
92%
0
10
20
30
40
Hudson MP et al. Circ Cardiovasc Qual Outcomes 2011;4:183-92
50
60
70
80
90
DAYS
Which Patients Cannot Afford a PPCI Delay?
PCI RELATED DELAY
(DB-DN) WHERE PCI
AND FIBRINOLYTIC
MORTALITY ARE
EQUAL (MIN)
180
0-120 Prehospital Delay (min)
121+
179
168
10,614
148
20,424
3,739
120
107
103
9,812
16,119
58
60
41,774
0
NonAnt MI
65+ YRS
Pinto DS et al. Circulation 2006; 114: 2019-2025
Ant MI
65+ YRS
NonAnt MI
< 65 YRS
40
43
19,517
5,296
Ant MI
< 65 YRS
Prehospital and In-Hospital Management
and Reperfusion Strategies
Primary-PCI
capable center
STEMI diagnosisa
PCI possible ˂120 min?
Preferably
˂60 min
Primary-PCI
EMS or non primary-PCI
capable center
Immediate transfer to PCI center
YES
NO
Preferably ≤90 min
(≤60 min in early presenters)
Rescue PCI
Preferably
≤30 min
Immediately
Immediate
transfer
to PCI center
NO
Successful fibrinolysis?
YES
Preferably 3-24 h
Coronary angiography
Immediate
fibrinolysis
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
ESC STEMI Guidelines 2012
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
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 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 Infarction
Impact of Routine Early Transfer for
PCI after Fibrinolysis
DEATH, REINFARCTION, WORSENING HEART FAILURE, OR CARDIOGENIC SHOCK
0.20
Standard treatment
0.15
HR 0.64; 95% CI, 0.47 - 0.87
Routine early PCI
0.10
Death, reinfarction, or recurrent ischemia
HR 0.65 (95% CI 0.44–0.96)
0.05
Early PCI
2.8 hrs
Standard treatment PCI 32.5 hrs
0.00
0
5
Cantor et al N Eng J Med 2009;360:2705
10
15
20
25
30
DAYS
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
TRITON TIMI 38 Prasugrel vs Clopidogrel
CV death / MI / Stroke
CUMULATIVE
INCIDENCE (%)
PLATO Ticagrelor vs Clopidogrel
CV death / MI / Stroke
CUMULATIVE
INCIDENCE (%)
Clopidogrel
15
12
Clopidogrel
11
10
Prasugrel
5
HR 0.79 95% CI 0.65-0.97 p=0.0221
P=0.0017
0
At risk 0
50
100
P=0.0221
150
200
250
300
350
400 450
DAYS FROM
RANDOMISATION
10
9
8
7
6
5
4
3
Ticagrelor
HR 0.87; 95% CI 0.75 - 1.01; P= 0.07
2
1
0
0
1
2
3
4
5
6
7
8
9
60% Primary PCI 30% Secondary delayed PCI
All primary PCI
No reduction of mortality, MI HR 0.70 p=0.01
Stent thrombosis HR 0.58 p=0.23
Mortality HR, 0.82; P=0.05 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
No increase in TIMI major or life threatening bleeding
Montelescot et al Lancet 2009; 373: 723
Steg et al Circulation. 2010;122:2131
10
11
12
MONTHS
Pre-Hospital Fibrinolysis + PCI vs Primary PCI for
Patients Unable to Undergo Primary PCI within 1
Hour
DEATH, SHOCK, CHF, OR REINFARCTION
% 20
15
Primary PCI
10
Fibrinolysis
5
RR 0.86; 95% CI, 0.68 -1.09; P = 0.21
0
0
5
10
15
STREAM Study Armstrong et al N Eng J Med 2013;368:1379
20
25
30
DAYS
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
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 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 Summary
2013 STEMI Management
STEMI patient who is a
candidate for reperfusion
Initially seen at
a PCI-capable
hospital
Send to cath lab for
primary PCI FMC-device
time ≤90 min
(Class 1, LOE: A)
DIDO
time≤30 min
Transfer for primary PCI
FMC-device time as soon
as Possible and
≤120 min
(Class 1, LOE: B)
Diagnostic angiogram
Medical
therapy only
PCI
Initially seen at a
non-PCI-capable
Hospital*
CABG
Administer fibrinolytic
agent within 30 min of
arrival when anticipated
FMC- device >120 min
(Class 1, LOE: B)
Urgent transfer for
PCI for patients
with evidence of
failed reperfusion
or reocclusion
(Class IIa, LOE: B)
Transfer for
angiography and
revascularization
within 3-24 h for other
patients as part of an
invasive strategyϮ
(Class IIa, LOE: B)
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