Bolus fibrinolytic therapy in acute myocardial infarction.
BACKGROUND
New bolus fibrinolytics derived from the human tissue-type plasminogen activator (tPA) have emerged as a means of dissolution of occlusive thrombosis associated with acute myocardial infarction.


OBJECTIVE
To review the new bolus fibrinolytic drugs derived from tPA: reteplase, lanoteplase, and tenecteplase.


METHODS
The MEDLINE, EMBASE, and Current Contents databases were searched for articles from 1983 to 2001, using the index terms pharmacokinetics, pharmacodynamics, plasminogen activator, reteplase, lanoteplase, and tenecteplase. Additional data sources included bibliographies of articles identified on MEDLINE, EMBASE, and Current Content, inquiry of experts and pharmaceutical companies, and preliminary data presented at recent national and international cardiology conferences.


METHODS
We selected for review studies that evaluated the pharmacokinetics and pharmacodynamics of reteplase, lanoteplase, and tenecteplase, and assessed the effects of these bolus fibrinolytic drugs on the angiographic and immediate and long-term outcomes of patients. Of 138 articles identified, 38 were analyzed.


METHODS
Data quality was determined by publication in the peer-reviewed literature or presentation at an official cardiology society-sponsored meeting.


RESULTS
Tenecteplase and reteplase are comparable with accelerated infusion recombinant tPA in terms of efficacy and safety but more convenient because they are administered by bolus injection. Lanoteplase and heparin bolus plus infusion is as effective as tPA with regard to mortality, but the rate of intracranial hemorrhage is significantly higher.


CONCLUSIONS
Given the ease of administration and the similar outcomes compared with accelerated infusion recombinant tPA, it is likely that a key component of contemporary reperfusion will include a bolus fibrinolytic.
Llevadot
J
J
TIMI Study Group, 333 Longwood Ave, Suite 402, Boston, MA 02115, USA.
Giugliano
R P
RP
Antman
E M
EM
D002986:Clinical Trials as Topic; D017023:Coronary Angiography; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077785:Tenecteplase; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; C081981:lanoteplase; C087896:reteplase; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase