title: Randomized comparison of coronary thrombolysis achieved with double-bolus reteplase (recombinant plasminogen activator) and front-loaded, accelerated alteplase (recombinant tissue plasminogen activator) in patients with acute myocardial infarction. The RAPID II Investigators.
abstract: BACKGROUND
  The therapeutic benefit of thrombolytic therapy has been shown to correlate directly with completeness (TIMI grade 3 flow) and speed of reperfusion of the infarct-related coronary artery. The purpose of the RAPID II study was to determine whether a double-bolus regimen of reteplase, a recently developed deletion mutant of wild-type tissue plasminogen activator, could improve 90-minute coronary artery patency rates achieved with the most successful standard regimen, an "accelerated" front-loaded infusion of alteplase.
  
  
  RESULTS
  Three hundred twenty-four patients with acute myocardial infarction were randomized to receive (along with intravenous heparin and aspirin) either a 10 plus 10 megaunits double bolus of reteplase or front-loaded alteplase. The primary end point of "patency at 90 minutes, graded according to the TIMI classification" was centrally assessed in a blinded fashion. Infarctrelated coronary artery patency (TIMI grade 2 or 3) and complete patency (TIMI grade 3) at 90 minutes after the start of thrombolytic therapy were significantly higher in the reteplase-treated patients (TIMI grade 2 or 3: 83.4% versus 73.3% for front-loaded alteplase-treated patients, P = .03; TIMI grade 3: 59.9% versus 45.2%, P = .01). At 60 minutes, the incidence of both, patency and complete patency, was also significantly higher in reteplase-treated patients (reteplase versus alteplase, TIMI grade 2 or 3: 81.8% versus 66.1%, P = .01; TIMI grade 3: 51.2% versus 37.4%, P < .03). Reteplase-treated patients required fewer acute additional coronary interventions (13.6% versus 26.5%, P < .01), and 35-day mortality was 4.1% for reteplase and 8.4% for alteplase (P = NS). There were no significant differences between reteplase and alteplase in bleedings requiring a transfusion (12.4% versus 9.7%) or hemorrhagic stroke (1.2% versus 1.9%).
  
  
  CONCLUSIONS
  Reteplase, when given as a double bolus of 10 plus 10 megaunits to patients with acute myocardial infarction, achieves significantly higher rates of early reperfusion of the infarct-related coronary artery and requires significantly fewer acute coronary interventions than front-loaded alteplase without an apparent increased risk of complications.
authors.affiliation: Medizinische Klinik III (Kardiologie), Universität Heidelberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Bode
authors.forename: R W
authors.initials: RW
authors.lastname: Smalling
authors.forename: G
authors.initials: G
authors.lastname: Berg
authors.forename: C
authors.initials: C
authors.lastname: Burnett
authors.forename: G
authors.initials: G
authors.lastname: Lorch
authors.forename: J M
authors.initials: JM
authors.lastname: Kalbfleisch
authors.forename: R
authors.initials: R
authors.lastname: Chernoff
authors.forename: L G
authors.initials: LG
authors.lastname: Christie
authors.forename: R L
authors.initials: RL
authors.lastname: Feldman
authors.forename: A A
authors.initials: AA
authors.lastname: Seals
authors.forename: W D
authors.initials: WD
authors.lastname: Weaver
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003328:Coronary Thrombosis / Q000188:drug therapy*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010960:Plasminogen Activators / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; C087896:reteplase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator