GUSTO-I: Global Utilization of Streptokinase and t-PA for Occluded coronary arteries - I
 
 Purpose
 To compare an aggressive thrombolytic strategy using accelerated tissue plasminogen activator (t-PA) with standard thrombolytic strategies in the treatment of acute myocardial infarction

 Reference
 The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673-82.

GUSTO-I: Global Utilization of Streptokinase and t-PA for Occluded coronary arteries - I - TRIAL DESIGN -
 
 Design: Randomized, parallel group

 Patients: 41,021 patients with AMI, <6h after onset of symptoms

 Follow up and endpoint: Primary endpoint death at 30 days

 Treatment: Four thrombolytic strategies compared:
Streptokinase (SK) (1.5 million U over 60 min) and SC heparin (12,500 U twice daily)
SK (1.5 million U over 60 min) and IV heparin (bolus 5000 U then 1000 U/h)
IV t-PA (1 mg/kg over 60 min, 10% bolus) and SK (1 million U over 60 min) and IV heparin (bolus 5000 U then 1000 U/h)
Accelerated t-PA (accelerated dose t-PA administered as bolus 15 mg, 0.75 mg/kg over 30 min (max 50 mg) and 0.5 mg/kg over 1h (max 35 mg)) and IV heparin (bolus 5000 U then 1000 U/h)

GUSTO-I: Global Utilization of Streptokinase and t-PA for Occluded coronary arteries - I - RESULTS -

Significant reduction in 30-day mortality with accelerated t-PA compared with the streptokinase (SK) and combination strategies
No significant difference between combination strategy and the two SK strategies (P=0.352), or between the two SK strategies (P=0.731)
Significant excess of hemorrhagic stroke for accelerated t-PA
    (P=0.03) and combination strategy (P<0.001), compared with the two SK-only strategies
However, combined endpoint of death or disabling stroke significantly lower with accelerated t-PA than with SK-only strategies (6.9% versus 7.8%; P=0.006)

GUSTO-I: Global Utilization of Streptokinase and t-PA for Occluded coronary arteries - I - RESULTS continued -

The GUSTO Investigators.
N Engl J Med
 1993;
329
:673
–
82.
Thirty-day mortality and stroke in the four treatment groups
Days after randomization
0
0
10
20
30
2
6
4
8
SK + IV heparin
SK + SC heparin
t-PA + SK +
IV heparin
Accelerated t-PA
Mortality (%)
GUSTO-I: Global Utilization of Streptokinase and t-PA for Occluded coronary arteries - I - RESULTS continued -

Thirty-day mortality and stroke in the four treatment groups
*P=0.001 for accelerated t-PA compared with both SK strategies
GUSTO-I: Global Utilization of Streptokinase and t-PA for Occluded coronary arteries - I - SUMMARY -

Although there was an excess of hemorrhagic stroke with t-PA plus heparin, compared with the other regimens, the combined 30-day endpoint of death or disabling stroke was significantly lower with accelerated t-PA

An aggressive thrombolytic strategy using accelerated t-PA (over 1.5 hours instead of 3 hours) with heparin, to produce earlier and sustained reperfusion, improves survival significantly compared with standard thrombolytic regimens comprising SK plus heparin