Fibrinolytic Therapy


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Dr. Nathania Marliani Kristanti, SpJP, FIHA. 3rd Pekanbaru Cardiology Update, August 24th 2013. Pangeran Hotel Pekanbaru. Learn more at

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Fibrinolytic Therapy

  1. 1. FIBRINOLYTICTHERAPY ACS - MedicalTreatment
  2. 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. 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. 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. 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. 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. 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. 8. 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)
  9. 9. 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
  10. 10. 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.
  11. 11. 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
  12. 12. 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
  13. 13. 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.
  14. 14. 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
  15. 15. 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
  16. 16. 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.
  17. 17. MONITORING • Tanda vital • Keluhan nyeri dada • EKG - aritmia reperfusi • Tanda-tanda perdarahan
  18. 18. 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)
  19. 19. SUCCESSFULL REPERFUSION? • resolution of chest pain -- sometimes inaccurate • serial assessment of 12-lead ECG -- more reliable • > 70% resolution of ST elevation • arrhythmia reperfusion -- AIVR
  20. 20. AIVR
  21. 21. • complete resolution of chest pain • ECG changes (>70% resolution of ST elevation) • a run of AIVR Highly specific for successful reperfusion <10%
  22. 22. RESCUE PCI