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i.
38
High-risk Patient
Bleeding Risk
Clinical Scenario
Very early presentation
< 1 hour
< or > 3 hours,
significant transfer
delay
< or > 3 hours, no
significant transfer
delay
Cardiogenic shock
Pulmonary edema
Electrical Instability
TIMI risk score > 5
Contraindications to
fibrinolytic therapy
Risk of bleeding /
Intracranial hemorrhage
Early or late
presentation, significant
transfer delay
Early or late
presentation, no
significant transfer
delay
Favored Therapy
Lysis
PCI
Recommendations by the Task Force on the management of STsegment elevation acute myocardial infarction of the European
Society of Cardiology4 for initial management of acute STEMI
are similar and are enlisted in Table1.
An angiotensin receptor blocker (ARB) should be administered
to STEMI patients who are intolerant of ACEIs and who have
either clinical or radiological signs of heart failure or LVEF
less than 0.40 [IC]. Valsartan and candesartan have established
efficacy for this recommendation.
Lipid management : A fasting lipid profile (or obtaining
one from recent past records for all STEMI patients) should be
performed within 24 hours of symptom onset and lipid-lowering
medication namely statins should be initiated before discharge
[IA].Treatment goals for LDL-C after STEMI should be < 100 mg/
dl [IA] and further reduction to < 70 mg/dl appears reasonable
[IIa-A]. Dietary advice on discharge should be given to all STEMI
patients especially emphasizing on < 7% of total calories from
saturated fat and < 200 mg/day of cholesterol [IA]. For patients
with non-HDL-C < 130 mg/dl and who also have HDL-C < 40 mg/
dl, special emphasis should be given on life-style modification
e.g. exercise, weight loss and smoking cessation [IB]. Drugs
like niacin or fibrate to raise HDL-C in this situation have IIa
recommendation (Level of evidence : B) after achieving LDL-C
< 100 mg/dl with statins. However, if triglycerides are 500 mg/
dl, niacin or fibrates should be initiated before LDL-lowering
therapy in order to prevent pancreatitis [IC].
i.
2.
3.
4.
i.
2.
Contraindications to Fibrinolysis
Absolute contraindications :
1.
2.
3.
4.
5.
6.
7.
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Relative contraindications :
1.
2.
3.
4.
5.
6.
Assessment of Reperfusion
(Non-invasive)
Relief of symptoms and maintenance or restoration of
haemodynamic and/or electric stability are most obvious features
of successful reperfusion following fibrinolytic therapy.
However, there are objective parameters to assess reperfusion
following fibrinolytic therapy.
ST-segment resolution : A close association with clinical
outcomes has been found with ST-segment resolution which is a
simple surrogate for both epicardial and myocardial reperfusion.
ST-resolution has typically been categorized as either present
(> 50%) or absent (< 50%) or as a three-way categorization
: complete (> 70% resolution), partial (30-70% resolution) or
none (< 30% resolution). Patients who achieve complete STresolution (> 70% resolution) are much more likely to have
normal TIMI grade 3 flow on angiography following fibrinolysis
compared to those with either partial or no ST-resolution.9 90%
of patients with complete ST-resolution had a patent infarct
related artery (IRA) and 70-80% achieved TIMI-3 flow. However,
conversely some patients with TIMI-3 flow were not found to
demonstrate complete ST-resolution since microvascular and
tissue reperfusion (assessed by myocardial contrast echo and
angiographic myocardial blush grading) were not achieved in
these cases resulting in significant myonecrosis. Thus, ultimately
ST-resolution is a good marker of tissue reperfusion after
fibrinolytic therapy. Consequently, GISSI-2 trials has clearly
shown that patients with > 50% ST-resolution were at much
lower risk of death compared to those with < 50% resolution at
30 days (3.5 vs. 7.4% HR 0.46, 95% CI 0.37 0.47).10
Biomarkers : With successful reperfusion, reflow of blood
allows faster clearance of necrotic proteins and hence CK-MB
and troponin levels peak earlier and decline faster. Since
troponin remains elevated longer (even weeks after a large
MI) than CK-MB and CK-MB returns to normal range within
40
METROPOLISES
& BIG TOWNS
PRIMARY
PCI
PRE-HOSPITAL
FIBRINOLYSIS
SMALL TOWN
HOSPITAL
(ED)
FIBRINOLYSIS
PHARMACOINVASIVE
PCI
PRE-HOSPITAL
FIBRINOLYSIS
VILLAGES
HOSPITAL
(ED)
FIBRINOLYSIS
RESCUE
PCI
Rescue PCI
Emergent PCI performed in a patient with evidence of failed
reperfusion with fibrinolytic therapy is called rescue PCI. Success
of rescue PCI in patients with moderate to large infarctions has
been demonstrated in terms of improved LV function and overall
clinical outcomes by review of early studies.13 More data are now
available from recent studies like MERLIN14 AND REACT.15
Despite impressive results with successfully conducted rescue
PCI, prognosis remains poor for those in whom rescue PCI is
unsuccessful.
As per ACC/AHA Guidelines (2004),1 following are the Class
I indications for rescue PCI :
a.
Bolus injection simplifies administration even in prehospital setting and reduces potential for medication errors.
2.
Pre-hospital Thrombolysis
Pre-hospital fibrinolysis is reasonable in settings in which
physicians or fully trained paramedics are present in the
ambulance or pre-hospital transport times are more than 60
minutes.
Analysis of studies in which > 6000 patients were randomized
to pre-hospital or in-hospital fibrinolysis has shown a significant
reduction (17%) in early mortality with pre-hospital treatment.11
A much longer mortality reduction was found in patients treated
within first 2 hours than in those treated later in a meta-analysis
of 22 trials.12
This is especially relevant in developing countries like India
with few tertiary care centres, predominantly rural population
and where people either have to travel long distances to avail of
medical facility or have to overcome urban traffic congestion.
However, administration of pre-hospital thrombolysis needs
tremendous infrastructure and a co-ordinated programme by
government or private sector or both. A proposed model for
Reperfusion therapy in AMI in various population segments
of India has been shown in Figure 1.
a.
SCAI Guidelines in its latest update (2009)3 has accorded class IIa
status to PCI in patients who have received fibrinolytic therapy
and who are at high risk (Level of Evidence : B). It has accorded
class IIb status to PCI after fibrinolytic therapy in patients who
are not at high risk. (Level of Evidence : C). Considerations
should be given in both groups to initiating a preparatory
antithrombotic (anti-coagulant plus anti-platelet) regimen before
and during patient transfer to the catheterization laboratory.
Adjunctive Therapy
A. With Fibrinolytic therapy
Antiplatelet co-therapy :
If not already on aspirin oral 150-325
mg soluble or chewable / non-enteric
coated) or i.v. dose of aspirin (250 mg
plus)
Clopidogrel oral loading dose (300
mg) if age 75 years
If age > 75 mg start with maintenance
dose of Clopidogrel (75 mg)
Antithrombin co-therapy with
alteplase, reteplase and tenecteplase :
Enoxaparin i.v. bolus followed 15 min
later by first s.c. dose, if age > 75 years
no i.v. bolus and start with reduced
first s.c. dose
If enoxaparin is not available, a
weight-adjusted bolus of i.v. heparin
followed by a weight-adjusted i.v.
infusion with first aPTT control after
3 hours
With streptokinase :
An i.v. bolus of fondaparinux
followed by an s.c. dose 24 hours later
or
Enoxaparin i.v. bolus followed 15
minutes later first s.c. dose, if age >
75 years, no i.v. bolus and start with
reduced first s.c. dose or
A weight-adjusted dose of i.v.
heparin followed by a weightadjusted infusion :
B. With Primary PCI :
Antiplatelet co-therapy :
Aspirin (oral dose of 150-325 mg or
i.v. dose of 250-500 mg)
Clopidogrel loading dose (300 mg,
preferably 600 mg)
Prasugrel (60 mg loading dose)
GPIIb/IIIa antagonist :
Abciximab
Tirofiban
Eptifibatide
Antithrombin therapy
Heparin
Bivalirudin (i.v. bolus of 0.75 mg /Kg
followed by infusion of 1.75 mg/Kg
hour)
Fondaparinux
Adjunctive devices :
Thrombus aspiration
41
Class of
Level of
Recommendation Evidence
I
IIa
Antiplatelet co-therapy :
If not already on aspirin oral (soluble
/ chewable / non-enteric coated) or i.v.
dose of aspirin if oral ingestion is not
feasible
Oral dose of clopidogrel (75 mg)
Antithrombin co-therapy :
2.5 mg i.v. bolus of fondaparinux
followed 24 hours later by an s.c. dose
If fondaparinux is not available,
enoxaparin i.v. bolus followed 15
minutes later by first s.c. dose; (1 mg /
Kg); if age > 75 years no i.v. bolus and
start with reduced s.c. dose (0.75 mg/
Kg) or
i.v. heparin followed by a weightadjusted i.v. infusion with first aPTT
control after 3 hours
Class of
Level of
Recommendation Evidence
I
References
I
IIa
IIa
IIa
1.
2.
3.
4.
5.
6.
7.
IIa
IIb
IIb
A
B
C
I
IIa
C
B
8.
III
9.
IIb
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