Thrombolytics

  • Streptokinase (and derivatives)
    Considered an inferior thrombolytic drug to tPA compounds as it is not given as a bolus and lacks fibrin specificity and antigenicity1
  • Alteplase (rt-PA)
    Recombinant form of human tissue plasminogen activator (tPA) with a 4-8 min plasma half-life.1 Improved outcomes in myocardial infarction treatment vs. streptokinase2,3
  • Reteplase (r-PA)
    Genetically modified rt-PA with longer half-life (13-16 min)1 and simplified administration. Failed to show clinical benefit over alteplase4
  • Tenecteplase (TNK)
    Longer plasma half-life, highest fibrin specificity, and resistance to plasminogen activator inhibitor-1 (PAI-1) vs rt-PA. Single bolus pharmacological reperfusion therapy, with equivalent efficacy and improved safety profile to alteplase5,6

Fibrin-specific and non fibrin-specific fibrinolytics
Mode of action

Fibrin-specific and non fibrin-specific fibrinolytics

Thrombolytics: from infusion to single bolus

Thrombolytics: from infusion to single bolus

 

Characteristics of an ideal thrombolytic agent would include the following:

  • Rapid acting
  • High efficacy in terms of both 60-90 min. vessel patency (TIMI grade flow)
  • Low incidence of adverse reactions, particularly bleeding and stroke
  • Low re-occlusion rate
  • Easy to administer (bolus vs. infusion)
  • Simple, patient-tailored dosage regimen
  • Good long-term effects on clinical outcome
  • Cost-effective
References: 
  1. Kunadian V & Gibson CM. Thrombolytics and myocardial infarction. Cardiovasc Ther 2012;30:e81-e88.
  2. Chesebro JH et al. Thrombolysis in Myocardial infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 1987;76:142-154.
  3. GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673-682.
  4. GUSTO III investigators. A comparison of reteplase with alteplase for acute myocardial infarction. N Engl J Med 1997;337:1118-1123.
  5. Cannon CP et al. TNK-tissue plasminogen activator compared with front-loaded alteplase in acute myocardial infarction: results of the TIMI 10B trial. Thrombolysis in myocardial infarction (TIMI) 10B investigators. Circulation 1998;98:2805-2814.
  6. ASSENT-2 investigators. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet 1999; 354:716-722.
  7. Van de Werf. The ideal fibrinolytic: can drug design improve clinical results? Eur Heart J 1999;20:1452-1458.
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