title: Survival outcomes 1 year after reperfusion therapy with either alteplase or reteplase for acute myocardial infarction: results from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) III Trial.
abstract: BACKGROUND
  New recombinant plasminogen activators have been developed to simulate the fibrinolytic action of the physiological serine protease tissue plasminogen activator (alteplase, t-PA), and have prolonged half-life features permitting bolus administration. One such activator, reteplase (r-PA), was compared with t-PA in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-III Trial.
  
  
  RESULTS
  At 1-year follow-up, survival status was ascertained in 97.4% of the 15 059 patients enrolled in the GUSTO-III trial. At 1 year, the mortality rate for the t-PA-assigned group was 11.06%, and for r-PA it was 11.20% (P:=0. 77). The absolute mortality difference of 0.14% has 95% CIs of -1. 21% to 0.93%. There were no significant differences in outcome by intention-to-treat for the 2 different plasminogen activators in the prespecified groups (age, infarct location, time-to-treatment). The absolute difference in mortality rates between t-PA and r-PA progressively narrowed over the predetermined observation times after random assignment; it was 0.31% at 24 hours, 0.26% at 7 days, 0.23% at 30 days, and 0.14% at 1 year. Of note, mortality rate in the trial between 30 days and 1 year in 13 883 patients was 4.02% and did not differ between the treatment groups. However, this mortality rate was substantially greater than in GUSTO-I, in which mortality rate for t-PA versus streptokinase between 30 days and 1-year was 2.97% (heart rate 1.36, 95% CI 1.23, 1.50, P:<0.001).
  
  
  CONCLUSIONS
  The r-PA and t-PA strategies yielded similar survival outcomes after 30 days in this trial. The increase in mortality rate during extended follow-up compared with previous trials may reflect higher-risk patients and highlights the need for improved secondary prevention strategies.
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. topole@ccf.org
authors.forename: E J
authors.initials: EJ
authors.lastname: Topol
authors.forename: E M
authors.initials: EM
authors.lastname: Ohman
authors.forename: P W
authors.initials: PW
authors.lastname: Armstrong
authors.forename: R
authors.initials: R
authors.lastname: Wilcox
authors.forename: A M
authors.initials: AM
authors.lastname: Skene
authors.forename: P
authors.initials: P
authors.lastname: Aylward
authors.forename: J
authors.initials: J
authors.lastname: Simes
authors.forename: A
authors.initials: A
authors.lastname: Dalby
authors.forename: A
authors.initials: A
authors.lastname: Betriu
authors.forename: C
authors.initials: C
authors.lastname: Bode
authors.forename: H D
authors.initials: HD
authors.lastname: White
authors.forename: J S
authors.initials: JS
authors.lastname: Hochman
authors.forename: H
authors.initials: H
authors.lastname: Emanuelson
authors.forename: A
authors.initials: A
authors.lastname: Vahanian
authors.forename: S
authors.initials: S
authors.lastname: Sapp
authors.forename: A
authors.initials: A
authors.lastname: Stebbins
authors.forename: D J
authors.initials: DJ
authors.lastname: Moliterno
authors.forename: R M
authors.initials: RM
authors.lastname: Califf
mesh_terms: D000208:Acute Disease; D015331:Cohort Studies; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D011994:Recombinant Proteins / Q000627:therapeutic use*; D015424:Reperfusion; D013300:Streptokinase / Q000627:therapeutic use*; D016019:Survival Analysis; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; C087896:reteplase; D013300:Streptokinase; D010959:Tissue Plasminogen Activator