Control Group: (n = 19287, 19287 analysed): streptokinase 1.5 x 10 6 U over 60 minutes with sc or iv heparin (combination of two groups, as no significant differences found)
Experimental Group: (n = 9695, 9695 analysed): accelerated tPA , bolus 15 mg, followed by infusion 0.75 mg/ kg (up to 50 mg) over 30 minutes, and 0.5 mg/ kg (up to 35 mg) over next 60 minutes and heparin
All patients received 160 mg or more chewable aspirin as soon as possible and 160 to 325 mg/d thereafter. 10 mg iv atenolol was given in two divided doses, with 50 to 100 mg given daily by mouth thereafter. All other medications and procedures were left to the discretion of the investigator.
96% followed for 12 months

The evidence

tPA vs streptokinase

Myocardial infarction: tPA was better than streptokinase at reducing mortality.

Clinical bottom line (level 1b)

  1. Patients with myocardial infarction who received tPA plus heparin were less likely to die than those given streptokinase plus heparin (NNT = 100 at 12 months) .
  2. There was no clear difference in the number of strokes with each treatment, but patients given tPA may have had an increased risk.
  3. Combining tPA and streptokinase was not clearly better than giving tPA alone.
Califf et al: Circulation 1996; 94 (6): 1233-1238
Expires March 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: multicentre, USA, Canada, New Zealand, Australia, France, The Netherlands, Poland, Belgium

37979 patients (aged range 52 to 69 years; mean 61, 76% male) acute myocardial infarction, presenting with ST-segment elevation within 6 hours of symptom onset who had survived for 30 days after treatment (from GUSTO I trial)

Excluded if
  • history of stroke
  • active or recent bleeding or major coagulation abnormality
  • recent trauma or major surgery
  • noncompressible vascular punctures
  • previous treatment with streptokinase or anistreplase


    • Control Group: (n = 19287, 19287 analysed): streptokinase 1.5 x 10 6 U over 60 minutes with sc or iv heparin (combination of two groups, as no significant differences found)
    Experimental Group: (n = 9695, 9695 analysed): accelerated tPA , bolus 15 mg, followed by infusion 0.75 mg/ kg (up to 50 mg) over 30 minutes, and 0.5 mg/ kg (up to 35 mg) over next 60 minutes and heparin
    All patients received 160 mg or more chewable aspirin as soon as possible and 160 to 325 mg/d thereafter. 10 mg iv atenolol was given in two divided doses, with 50 to 100 mg given daily by mouth thereafter. All other medications and procedures were left to the discretion of the investigator.
    96% followed for 12 months

    The evidence

    tPA vs streptokinase
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death 12 months 1948
    (10.1%)    		 882
    (9.10%)    		 10%
    (3% to 16%)    		 1.00%
    (0.29% to 1.72%)    		 100
    (58 to 350)
    any stroke 12 months 163
    (0.85%)    		 97
    (1.00%)    		 -18%
    (-52% to 8%)    		 -0.16%
    (-0.39% to 0.08%)    		 -640
    (NNT = 1200 to infinity;
    NNH = 260 to infinity)

    tPA and streptokinase vs tPA alone
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    mortality 12 months 882
    (9.10%)    		 950
    (9.90%)    		 -9%
    (-19% to 0%)    		 -0.80%
    (-1.63% to 0.03%)    		 -130
    (NNT = 3800 to infinity;
    NNH = 61 to infinity)

  • A worst-case analysis (taking all missing patients as dead) makes no significant difference to these results.

    • Citation

    1. Califf RM, White HD, Van de Werf F, et al: One-year results from the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial. Circulation 1996; 94 (6): 1233-1238
    Contributor: Clare Wotton and Bob Phillips, December 2000
    Reviewer:

    Clinical Question.
    Patient MI
    Intervention or Exposure tPA
    Comparison streptokinase
    Outcome death, stroke
Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
death 12 months 1948
(10.1%)		 882
(9.10%)		 10%
(3% to 16%)		 1.00%
(0.29% to 1.72%)		 100
(58 to 350)
any stroke 12 months 163
(0.85%)		 97
(1.00%)		 -18%
(-52% to 8%)		 -0.16%
(-0.39% to 0.08%)		 -640
(NNT = 1200 to infinity;
NNH = 260 to infinity)

tPA and streptokinase vs tPA alone
Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
mortality 12 months 882
(9.10%)		 950
(9.90%)		 -9%
(-19% to 0%)		 -0.80%
(-1.63% to 0.03%)		 -130
(NNT = 3800 to infinity;
NNH = 61 to infinity)

A worst-case analysis (taking all missing patients as dead) makes no significant difference to these results.

Citation

  1. Califf RM, White HD, Van de Werf F, et al: One-year results from the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial. Circulation 1996; 94 (6): 1233-1238
Contributor: Clare Wotton and Bob Phillips, December 2000
Reviewer:

Clinical Question.
Patient MI
Intervention or Exposure tPA
Comparison streptokinase
Outcome death, stroke