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) IIItrial

Background-New recombinant plasminogen activators have been developed to si mulate the fibrinolytic action of the physiological serine protease tissue plasminogen activator (alteplase, t-PA), and have prolonged half-life featu res 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. Methods and 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, t he mortality rate for the t-PA-assigned group was 11.06%, and for r-PA it w as 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 int ention-to-treat for the 2 different plasminogen activators in the prespecif ied groups (age, infarct location, time-to-treatment). The absolute differe nce in mortality rates between t-PA and r-PA progressively narrowed over th e 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 w as 4.02% and did not differ between the treatment groups. However, this mor tality rate was substantially greater than in GUSTO-I, in which mortality r ate for t-PA versus streptokinase between 30 days and 1-year was 2.97% (hea rt 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 a nd highlights the need for improved secondary prevention strategies.