Myocardial infarction: tPA and heparin prevented more deaths than streptokinase and heparin, but caused more strokes.

Clinical bottom line (level 1b)

  1. Patients with a suspected myocardial infarction who received streptokinase and iv heparin compared with streptokinase and subcutaneous heparin were more likely to have a severe bleed (NNH = 510 at 30 days) . There was no clear effect on mortality or stroke.
  2. Patients who received accelerated tPA and iv heparin compared with streptokinase and sc heparin were less likely to die (NNT = 76 at 12 months) , but were more likely to have a stroke (NNH = 300 at 30 days) .
  3. Patients who received tPA, streptokinase and iv heparin compared with tPA and iv heparin were more likely to die (NNH = 94 at 12 months) , but were not clearly more likely to have a stroke or a severe bleed.
The GUSTO investigators : New England Journal of Medicine 1993; 329 (10): 673-682
Califf et al: Circulation 1996; 94: 1233-1238
Expires March 2003

The study

Unblinded ?concealed randomised trial ?with intention-to-treat
Setting: 1081 acute hospitals in North America, Europe, Australia, New Zealand and Israel

41021 patients (aged mean 62, 75% male) presenting with chest pain lasting at least 20 minutes within 6 hours of symptom onset, and ST elevation of 0.1 mm or more in 2 or more limb leads or 0.2 mV or more in 2 precordial leads on ECG.

Excluded if
  • severe hypertension (systolic 180 mmHg or more, unresponsive to therapy)
  • previous stroke
  • active bleeding
  • previous treatment with anistreplase or streptokinase
  • recent trauma or major surgery
  • previous participation in the trial
  • non-compressible vascular punctures


Control Group: (n = 9841, 9841 analysed): streptokinase 1.5 million units over 60 minutes and subcutaneous heparin 12500 units twice daily
Experimental Group: (n = 10410, 10410 analysed): streptokinase 1.5 million units and intravenous heparin bolus of 5000 units followed by an infusion of 1000 units per hour adjusted so aPTT 60 to 85 seconds.
Experimental Group: (n = 10396, 10396 analysed): accelerated tPA bolus of 15 mg, then 0.75 mg/kg over 30 minutes (not exceeding 50 mg) and followed by 0.5 mg/kg up to 35 mg over 60 minutes with intravenous heparin bolus of 5000 units, followed by 1000 units per hour adjusted so aPTT 65 to 80 seconds
Experimental Group: (n = 10374, 10374 analysed): tPA and streptokinase and heparin

96% followed for 12 months
Outcome notes:
  • death : streptokinase and iv heparin v. streptokinase and sc heparin
  • death : streptokinase and iv heparin v. streptokinase and sc heparin
  • stroke : streptokinase and iv heparin v. streptokinase and sc heparin
  • severe bleeding : streptokinase and iv heparin v. streptokinase and sc heparin
  • death : tPA and heparin v. streptokinase and sc heparin
  • death : tPA and heparin v. streptokinase and sc heparin
  • stroke : tPA and heparin v. streptokinase and sc heparin
  • severe bleeding : tPA and heparin v. streptokinase and sc heparin
  • death : tPA and streptokinase v. tPA
  • death : tPA and streptokinase v. tPA
  • stroke : tPA and streptokinase v. tPA
  • severe bleeding : tPA and streptokinase v. tPA

The evidence

streptokinase and iv heparin v. streptokinase and sc heparin
Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
death 30 days 705
(7.20%)		 768
(7.40%)		 -3%
(-13% to 7%)		 -0.20%
(-0.92% to 0.51%)		 -500
(NNT = 110 to infinity;
NNH = 200 to infinity)
death 12 months 994
(10.2%)		 1051
(10.1%)		 0%
(-8% to 8%)		 0.02%
(-0.81% to 0.85%)		 5300
(NNT = 120 to infinity;
NNH = 120 to infinity)
stroke 30 days 118
(1.22%)		 144
(1.40%)		 -15%
(-46% to 10%)		 -0.18%
(-0.50% to 0.13%)		 -550
(NNT = 200 to infinity;
NNH = 750 to infinity)
severe bleeding 30 days 26
(0.30%)		 46
(0.50%)		 -66%
(-170% to -3%)		 -0.20%
(-0.38% to -0.01%)		 -510
(-7500 to -260)

tPA and heparin v. streptokinase and sc heparin
Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
death 30 days 705
(7.20%)		 652
(6.30%)		 12%
(3% to 21%)		 0.89%
(0.20% to 1.59%)		 110
(63 to 500)
death 12 months 994
(10.2%)		 914
(8.84%)		 13%
(5% to 20%)		 1.31%
(0.50% to 2.12%)		 76
(47 to 200)
stroke 30 days 118
(1.22%)		 159
(1.55%)		 -27%
(-61% to -1%)		 -0.33%
(-0.66% to -0.01%)		 -300
(-10200 to -150)
severe bleeding 30 days 26
(0.30%)		 37
(0.40%)		 -34%
(-121% to 19%)		 -0.10%
(-0.27% to 0.07%)		 -990
(NNT = 370 to infinity;
NNH = 1400 to infinity)

tPA, streptokinase and heparin v. tPA and heparin
Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
death 30 days 652
(6.30%)		 723
(7.00%)		 -11%
(-23% to 0%)		 -0.70%
(-1.38% to -0.02%)		 -140
(-5600 to -73)
death 12 months 914
(8.84%)		 1022
(9.90%)		 -12%
(-22% to -3%)		 -1.06%
(-1.85% to -0.27%)		 -94
(-380 to -54)
stroke 30 days 159
(1.55%)		 168
(1.64%)		 -6%
(-31% to 15%)		 -0.09%
(-0.43% to 0.25%)		 -1100
(NNT = 230 to infinity;
NNH = 400 to infinity)
severe bleeding 30 days 37
(0.40%)		 55
(0.60%)		 -49%
(-130% to 2%)		 -0.20%
(-0.40% to 0.01%)		 -510
(NNT = 250 to infinity;
NNH = 16000 to infinity)

Citation

  1. The GUSTO investigators , : An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. New England Journal of Medicine 1993; 329 (10): 673-682
  2. 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-1) Trial. Circulation 1996; 94: 1233-1238
Search Terms: ?
Contributor: Chris Ball and Clare Wotton, February 2000
Reviewer:

Clinical Question.
Patient myocardial infarction
Intervention or Exposure tPA, streptokinase, heparin
Outcome death, stroke