1) The document discusses fibrinolytic therapy for ST-elevation myocardial infarction (STEMI). STEMI is defined as new ST elevation and biomarkers of necrosis.
2) Immediate reperfusion therapy with either primary percutaneous coronary intervention (PCI) or fibrinolysis is recommended for STEMI patients. The goals are to perform primary PCI within 90 minutes of first medical contact or give fibrinolysis within 30 minutes.
3) Several fibrinolytic agents are discussed including alteplase, reteplase, tenecteplase, and streptokinase. Their properties, dosages, and effectiveness are compared. Successful reperfusion is assessed by resolution of symptoms and ECG changes.
2. STEMI
• a clinical syndrome defined by characteristic
symptoms of myocardial ischemia in association
with persistent electrocardiographic (ECG) ST
elevation and subsequent release of biomarkers of
myocardial necrosis.
• new ST elevation at the J point in at least 2
contiguous leads of ≥2 mm (0.2 mV) in men or
≥1.5 mm (0.15 mV) in women in leads V2–V3
and/or of ≥1 mm (0.1 mV) in other contiguous
chest leads or the limb leads
3. •Any patients with symptoms of chest
pain suspected to be cardiac origin
•ECG should be obtained within 10
minutes
•interpreted promptly
•determine eligibility for reperfusion
therapy
4. • acute myocardial infarction (MI) should be used when there is
evidence of myocardial necrosis in a clinical setting consistent
with acute myocardial ischaemia
• Detection of a rise and/or fall of cardiac biomarker values [preferably cardiac
troponin (cTn)] with at least one value above the 99th percentile upper reference
limit (URL) and with at least one of the following:
• Symptoms of ischaemia
• New or presumed new significant ST-segment–T wave (ST–T) changes or new left bundle
branch block (LBBB).
• Development of pathological Q waves in the ECG.
• Imaging evidence of new loss of viable myocardium or new regional wall motion
abnormality.
• Identification of an intracoronary thrombus by angiography or autopsy.
Third universal definition of myocardial infarction; Thygesen et al; European Heart Journal 2012
5. Yes No
No
Preferably
<60 min
Immediately
Preferably 3–24 h
Preferably
≤90 min
(≤60 min in early presenters) Preferably
≤30 min
a
The 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).
Immediate transfer
to PCI center
Immediate transfer
to PCI center
Yes
STEMI diagnosisa
Primary-PCI capable center
Primary-PCI
Coronary angiography
Rescue PCI
EMS or non primary-PCI
capable center
Immediate
fibrinolysis
Successful
fibrinolysis?
PCI possible <120 min?
Cath = catheterizationlaboratory; EMS = emergency medical system; FMC = first medical contact; PCI = percutaneouscoronary intervention; STEMI = ST-segment elevation myocardial infarction.
Figure 2 Prehospital and in-hospital management, and reperfusion strategies within 24 h of FMC (adapted from Wijns et al.).4
6. Figure 1. Reperfusion therapy for patients with STEMI. The bold arrows and boxes are the preferred strategies. Performance of PCI is
2013 ACCF/AHA STEMI Guideline Executive Summary January 29, 2013:xxx–xx
7. possible, for immediate defibrillation if needed. In addition, early
provision of therapy, particularly reperfusion therapy, is critical to
its benefit.38
Thus, minimizing delays is associated with improved
outcomes. In addition, delays to treatment are the most readily avail-
able, measurable index of quality of care in STEMI; they should be
than patient delay. It is an indicator of quality of care and a pre-
dictor of outcomes.39
If the reperfusion therapy is primary PCI,
the goal should be a delay (FMC to wire passage into the culprit
artery) of ≤90 min (and, in high-risk cases with large anterior
infarcts and early presenters within 2 h, it should be
Symptom onset FMC Diagnosis Reperfusion therapy
10 min
Patient delay
System delay
Wire passage in culprit artery
if primary PCI
Bolus or infusion
start if thrombolysis
Time to reperfusion therapy
All delays are related to FMC (first medical contact)
Figure 1 Components of delay in STEMI and ideal time intervals for intervention.
8.
9.
10.
11. CONTRAINDICATIONS TO
FIBRINOLYTIC TX
Absolute
Previous intracranial haemorrhage or stroke of unknown origin at any time
Ischaemic stroke in the preceding 6 months
Central nervous system damage or neoplasms or atrioventricular malformation
Recent major trauma/surgery/head injury (within the preceding 3 weeks)
Gastrointestinal bleeding within the past month
Known bleeding disorder (excluding menses)
Aortic dissection
Non-compressible punctures in the past 24 h (e.g. liver biopsy, lumbar puncture)
12. CONTRAINDICATIONS TO
FIBRINOLYTIC TX
Relative
Transient ischaemic attack in the preceding 6 months
Oral anticoagulant therapy
Pregnancy or within 1 week postpartum
Refractory hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg)
Advanced liver disease
Infective endocarditis
Active peptic ulcer
Prolonged or traumatic resuscitation
13.
14. Alteplase (tPA)
• Tissue plasminogen activator (Actilyse®)
• enzyme that binds to fibrin with a greater affinity than
streptokinase or urokinase
• convert plasminogen to plasmin on the fibrin surface.
• relatively “clot selective”
• The very short half-life of alteplase mandates co-therapy with
intravenous heparin to avoid reocclusion.
• In the GUSTO trial mortality was 14% lower (1% absolute
decrease) with tPA compared with streptokinase.
15. Alteplase (tPA)
• Accelerated regimen (weight-based)
• Patients > 67 kg
• 15 mg bolus over 1-2 minutes
• infusion 50 mg over 30 minutes, 35 mg over 1 hour
• Patients ≤ 67 kg
• 15 mg bolus over 1-2 minutes
• 0.75 mg/kg over 30 minutes, 0.5 mg/kg over 1 hour
O’Gara, 2013 ACCF/AHA
16. RETEPLASE
• recombinant plasminogen activator (rPA) - Retavase®
• less fibrin-specific mutation
• has a longer half-life
• no mortality benefit
• Double bolus regiment :
• 10 U over 10 minutes and another 10 U 30 minutes apart
17. TENECTEPLASE
• Tenecteplase (TNK-tPA) is a genetically engineered,
multiple point mutant of tPA
• Longer plasma half-life allowing for a single intravenous
bolus injection
• It is also 14 times more fibrin specific and has an 80 fold
higher resistance to inhibition by plasminogen activator
inhibitor 1 (PAI-1) than standard tPA.
• Easier and faster to administer
• These advantages have made tenecteplase the fibrinolytic
agent of choice in many hospitals in the United States.
18. STREPTOKINASE
• a single chain polypeptide derived from culture
filtrate of beta- haemolytic streptococci of group C
• high doses are necessary to neutralize the
plasma levels of antistreptococcal antibodies
• Form a 1:1 complex with plasminogen that
convert to plasmin
19.
20.
21. Streptokinase Alteplase Reteplase Tenecteplase
Fibrin selective No Yes Yes Yes > tPA
Plasminogen
binding
Indirect Direct Direct Direct
Duration of
infusion (min)
60 90 10 + 10 5-10 sec
Half-life (min) 23 <5 13-16 20
Fibrinogen
breakdown
4+ 1-2+ Not known >tPA
Early heparin Probably yes Yes Yes Yes
Hypotension Yes No No No
Allergic
reactions
Yes No No No
Approximate
current cost/
dose
$750 $5863 $5212 $3848
TIMI flow grade
3 in 90 min
32% 45%-54% 60% ≈tPA
Opie, 2013
22. HOW TO PREPARE
1.Slowly add 5 mL Sodium Chloride Injection or 5% Dextrose Injection to the
Streptokinase vial, directing the diluent at the side of the vacuum-packed
vial rather than into the drug powder.
2.Roll and tilt the vial gently to reconstitute. Avoid shaking. (Shaking may
cause foaming.)
3.Withdraw the entire reconstituted contents of the vial; slowly and carefully
dilute further to a total volume of 100 mL. Avoid shaking and agitation on
dilution.
4.Because Streptokinase, contains no preservatives, it should be
reconstituted immediately before use. The solution may be used for direct
intravenous administration within eight hours following reconstitution if
stored at 2-8°C.
5.Do not add other medication to the container of Streptase, Streptokinase.
6.Unused reconstituted drug should be discarded.
27. COMPLICATIONS
• most serious - intracerebral hemorrhage (0.5-0.7%)
• major risk factors :
• age > 75 years
• hypertension
• low body weight
• female gender
• coagulopathy (prior use of anticoagulants)
28. SUCCESSFULL REPERFUSION?
• resolution of chest pain -- sometimes inaccurate
• serial assessment of 12-lead ECG -- more reliable
• > 70% resolution of ST elevation
• arrhythmia reperfusion -- AIVR
31. • complete resolution of chest pain
• ECG changes (>70% resolution of ST elevation)
• a run of AIVR
Highly specific for successful reperfusion
<10%
