An International Randomized Trial Comparing Four Thrombolytic Strategies for Acute Myocardial Infarction
Topic: Thrombolytics in acute coronary syndrome
- Determine the role of streptokinase and tissue plasminogen activator with intravenous vs subcutaneous heparin as adjunctive therapy in acute myocardial infarction.
- Multicenter, randomized, open label, comparative trial
- Streptokinase (1.5 million U over 60 min) with subcutaneous heparin (12,500U twice daily 4 hours after thrombolytic therapy).
- Streptokinase (1.5 million U over 60 min) with IV heparin (5000U bolus then 1000U per hour ACT adjusted.
- Accelerated t-PA (IV 15 mg bolus, then 0.75 mg/kg over 30 min, not to exceed 50 mg, then 0.5 mg/kg, up to 35 mg, over the next 60 min.
- Combination of t-PA (1 mg/kg over 60 min) and streptokinase (1.0 million U over 60 min) given simultaneously, with IV heparin (dose noted above).
- 41,021 patients
- Presenting with symptoms less than 6 hours after onset (chest pain > 20 min with ST- elevation > 0.1 mV in two or more limb leads or > 0.2 mV in two or more continuous precordial leads.
- Previous stroke, active bleeding, previous treatment with streptokinase or anistreplase, recent trauma or major surgery, previous participation in the trial, or noncompressible vascular punctures, severe uncontrolled hypertension (SBP > 180 mm Hg).
- 30 days
- All-cause mortality at 30 days.
- Bleeding defined as: severe or life-threatening (CNS bleed or hemodynamic compromise), moderate bleeding (need for transfusion), minor bleeding (not requiring transfusion).
- Combined end points of death and nonfatal stroke, death and nonfatal hemorrhagic stroke, and death and nonfatal disabling stroke.
Primary outcome: all-cause mortality at 30 days
- 7.2% vs. 7.4% vs. 6.3% vs. 7.0% (risk reduction 14%; 95% CI 5.9-21.3%; P=0.001; NNT=100)
- No difference between groups receiving SK, P=0.731
- [tPA + heparin] better than [tPA + SK + heparin] with risk reduction 10%, 95% CI 6.3-7.0%, P=0.04
- All-cause mortality at 30 days or nonfatal stroke: 7.9% vs. 8.2% vs. 7.2% vs. 7.9% (P=0.006; NNT 118)
- All-cause mortality at 30 days or nonfatal hemorrhagic stroke: 7.4% vs. 7.6% vs. 6.6% vs. 7.4% (P=0.004; NNT 111)
- All-cause mortality at 30 days or nonfatal disabling stroke: 7.7% vs. 7.9% vs. 6.9% vs. 7.6% (P=0.006; NNT 111)
Adverse event of stroke: 1.22% vs. 1.40% vs. 1.55% vs. 1.64% (P=0.09)
- Hemorrhagic: 0.49% vs. 0.54% vs. 0.72% vs. 0.94% (P=0.03; NNH 489)
- Non-hemorrhagic: 0.53% vs. 0.65% vs. 0.64% vs. 0.53% (P=0.57)
- Hemorrhagic conversion: 0.04% vs. 0.05% vs. 0.06% vs. 0.08% (P=0.62)
- Unknown: 0.15% vs. 0.16% vs. 0.13% vs. 0.10% (P=0.54)
- Severe or life-threatening: 0.3% vs. 0.5% vs. 0.4% vs. 0.6% (P=0.31)
- Moderate: 5.6% vs. 5.8% vs. 5.1% vs. 5.6% (P=0.04; NNH 167)
- Moderate or worse: 5.8% vs. 6.3% vs. 5.4% vs. 6.1% (P=0.02; NNH 154)
TAKE AWAY: Among patients with ACS, rapidly administered tPA in addition to heparin and ASA reduces all-cause mortality at 30 days when compared ASA and heparin with either streptokinase or slowly-administered tPA and streptokinase.