VIMS Journal: December 2015

Editorial

In Search of an Ideal Thrombolytic Agent

Dr. Soumitra Kumar

In 1933, Dr. William Tillett discovered streptokinase (SK) through sheer chance when he observed that streptococci agglutinated plasma not serum[1]. In 1958, Fletcher first reported the use of thrombolytic therapy for management of AMI[2]. The GISSI and ISIS trials firmly established the efficacy of intravenous SK in management of patients with AMI[3-5]. Subsequent search for ideal tyhrombolytic agent led to emergence of second and third generation thrombolytics, namely alteplase (t-PA), reteplase (rPA) and tenecteplase (TNK) amongst others.Table below shows a comparison of common fibrinolytic agents[6] :

An article in this issue of the journal by J. Nawaz et al compares use of thrombolytics in Ramakrishna Mission Seva Pratishthan. In this study of 245 patients with ST-elevation myocardial infarction, success rate of Rateplase has been reported as highest at 91.66% and success rates of Tenecteplase have been reported as comparable to that of streptokinase (80.76% vs, 72.75%). However, profile of patients in each group in terms of age, sex, time of presentation after onset of chest pain, co-morbid conditions etc. have not been described. Assessment of success without multivariate analysis of these factors is not acceptable on scientific ground. Same logic applies to assessment of bleeding complications.

Comparison of Common Fibrinolytic Agents[6]:

Parameter Streptokinase (SK) Ateplase (tPA) Reteplase (rPA) TNK t-PA
Dose 1.5 MU in 30-60 min. Upto 100mg in 90 min. 10 Ux2 (30 min.)apart each other 2 minutes. 30-50mg (based on weight)
Bolus administration No No Yes Yes
Antigenic (Allergic reactions) Yes No No No
Systemic fibrinogen depletion Marked Mild Moderate Minimal
90 min. patency rate (%) ≅50 ≅75 ≅75 ≅75
TIMI grade 3 flow (%) 32 54 60 63
Cost per dose (US $) 568 2,750 2,750 2,750 for 50mg

However, major international trials with TNKtPA and rPA do not report major differences in terms of success (vide table) and complications although direct comparisons have not been made. The ideal thrombolytic agent still continue to elude us. Future research might see development of optimal thrombolytic strategy with ability of maximal reperfusion and with minimal bleeding and re-occlusion complications. Awaiting such breakthrough, at present time patients presenting within 4 hours of symptom onset to non-pCI centres (where delay to invasive strategy is expected), speed of reperfusion of infarct vessel is of paramount importance and bolus fibrinolytic agent (ie. TNK-tPA or rPA) is to be preferred. For those presenting between 4 hours and 12 hours after onset of chest discomfort, speed of reperfusion of the infarct vessel is of lesser importance and SK and accelerated t-PA are equivalent options given the difference in costs; Infact in patients with low mortality risk but an increased risk of intracerebral haemorrhage (ICH) SK is probably preferable to t-PA.

References
  1. Vijaylakshmi Kunadian, C Michael Gibson. Thrombolytics and Myocardial Infarction. Cardiovascular Therapeutics 2012; 30:381-388.

  2. Fletcher AB, Alkjaersign N, Smymiotis FE, Sherry S. The treatment of patients suffering from early myocardial infarction with massive and prolonged streptokinase therapy. Trans Assoc Am Physicians. 1958;71:287-96.

  3. Gruppo italiano per IO Studio della Streptochinasi nell’ infarto Miocardio (GISSI). Effectiveness of intravenousthrombolytic treatment in acute myocardial infarction. Lancet 1986;1:397-402.

  4. ISIS-2 (Second International Study of Infarct Survival) collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both or neither among 17,187 cases of suspected acute myocardial infarction ISIS- 2 Lancet. 1988;2:349-60.

  5. Baigent C, collins R, Appleby P et al. The ISIS-2 (Second International Study of Infarct Srvival) Collaborative Group. ISIS-2:10 year survival among patients with suspected acute myocardial infarction in randomized comparison of intravenous streptokinase, oral aspirin, both or neither, BMJ.1998; 316:1337-43.

  6. Antman EM, Anbe DT, Armstrong PW et al. ACC/AHA guidelines for the management of patients with STelevation myocardial infarction : A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.

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