title: Sixty-minute alteplase protocol: a new accelerated recombinant tissue-type plasminogen activator regimen for thrombolysis in acute myocardial infarction.
abstract: OBJECTIVE
  Our aim was to design and evaluate a new and easily administered recombinant tissue-type plasminogen activator (rt-PA) regimen for thrombolysis in acute myocardial infarction (AMI) based on established pharmacokinetic data that improve the reperfusion success rate.
  
  
  BACKGROUND
  Rapid restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow is a primary predictor of mortality after thrombolysis in AMI. However, TIMI grade 3 patency rates 90 min into thrombolysis of only 50% to 60% indicate an obvious need for improved thrombolytic regimens.
  
  
  METHODS
  Pharmacokinetic simulations were performed to design a new rt-PA regimen. We aimed for a plateau tissue-type plasminogen activator (t-PA) plasma level similar to that of the first plateau of the Neuhaus regimen. These aims were achieved with a 20-mg rt-PA intravenous (i.v.) bolus followed by an 80-mg i.v. infusion over 60 min (regimen A). This regimen was tested in a consecutive comparative trial in 80 patients versus 2.25 10(6) IU of streptokinase/60 min (B), and 70 mg (C) or 100 mg (D) of rt-PA over 90 min. Subsequently, a confirmation trial of regimen A in 254 consecutive patients was performed with angiographic assessment by independent investigators of patency at 90 min.
  
  
  RESULTS
  The comparative phase of the trial yielded, respectively, TIMI grade 3 and total patency (TIMI grades 2 and 3) of 80% and 85% (regimen A), 35% and 50% (B), 50% and 55% (C) and 60% and 70% (D). In the confirmation phase of the trial, regimen A yielded 81.1% TIMI grade 3 and 87.0% total patency. At follow-up angiography 7 (4.1%) of 169 vessels had reoccluded. In-hospital mortality rate was 1.2%. Nadir levels of fibrinogen, plasminogen and alpha2-antiplasmin were 3.6 +/- 0.8 mg/ml, 60 +/- 21% and 42 +/- 16%, respectively (mean +/- SD). Fifty-seven patients (22.4%) suffered from bleeding; 3.5% needed blood transfusions.
  
  
  CONCLUSIONS
  The 60-min alteplase thrombolysis in AMI protocol achieved a TIMI grade 3 patency rate of 81.1% at 90 min with no indication of an increased bleeding hazard; it was associated with a 1.2% overall mortality rate. These results are substantially better than those reported from all currently utilized regimens. Head to head comparison with established thrombolytic regimens in a large-scale randomized trial is warranted.
authors.affiliation: Franz Volhard Clinic, Virchow Klinikum-Charité, Humboldt University of Berlin, Germany. gulba@fvk.-berlin.de
authors.forename: D C
authors.initials: DC
authors.lastname: Gulba
authors.forename: P
authors.initials: P
authors.lastname: Tanswell
authors.forename: R
authors.initials: R
authors.lastname: Dechend
authors.forename: M
authors.initials: M
authors.lastname: Sosada
authors.forename: A
authors.initials: A
authors.lastname: Weis
authors.forename: J
authors.initials: J
authors.lastname: Waigand
authors.forename: F
authors.initials: F
authors.lastname: Uhlich
authors.forename: S
authors.initials: S
authors.lastname: Hauck
authors.forename: S
authors.initials: S
authors.lastname: Jost
authors.forename: W
authors.initials: W
authors.lastname: Rafflenbeul
authors.forename: P R
authors.initials: PR
authors.lastname: Lichtlen
authors.forename: R
authors.initials: R
authors.lastname: Dietz
mesh_terms: D001780:Blood Coagulation Tests; D017023:Coronary Angiography; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D010960:Plasminogen Activators / Q000008:administration & dosage* / Q000097:blood; D011446:Prospective Studies; D013300:Streptokinase / Q000008:administration & dosage / Q000097:blood; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000097:blood; D014654:Vascular Patency
chemical_list: D013300:Streptokinase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator