Randomised Trial of Intravenous Streptokinase, Oral Aspirin, Both, or Neither among 17187 Cases of Suspected Acute Myocardial Infarction
Topic: Thrombolytics in acute coronary syndrome
- In patients with suspected acute MI, what is separate and combined effect of streptokinase and of aspirin in decreasing the risk of vascular mortality?
- Multicenter, double-blinded, two-by-two factorial, randomized, placebo-controlled trial
- Streptokinase (1.5 million units infused over 1 hour), with or without aspirin (162.5 mg) for 1 month.
- Placebo streptokinase with or without aspirin (162.5 mg) for 1 month.
- 17,187 patients
- Suspected acute MI within 24 hours of symptom onset, no clear indication for, or contraindication to, streptokinase or aspirin.
- History of stroke, history of GI bleed or PUD, recent arterial puncture, recent severe trauma, severe persistent hypertension, or allergy to streptokinase or aspirin.
- 15 months
- Vascular mortality at 5 weeks.
- Nonfatal reinfarction, bleeding requiring transfusion, nonfatal stroke, cerebral hemorrhage.
Primary outcomes: Vascular mortality at 5 weeks
- Streptokinase vs. placebo: 9.2% vs 12.0% (RR 0.77, 2P<0.00001, NNT=35)
- Aspirin vs. placebo: 9.4% vs 11.8%, (RR 0.80, 2P<0.00001, NNT=42)
- Aspirin and streptokinase vs. placebo: 8.0% vs 13.2% (RR 0.60, 2P<0.0001, NNT=19)
- Streptokinase vs. placebo: 1.8% vs. 1.1%
- Aspirin vs. placebo: 1.0% vs. 2.0%
- Streptokinase and aspirin vs. placebo: 1.1% vs. 1.6%
Bleeds requiring transfusion
- Streptokinase vs. placebo: 0.5% vs. 0.2% (2P <0.001)
- Aspirin vs. placebo: 0.4% vs. 0.4% (P=NS)
- Streptokinase and aspirin vs. placebo: 0.6% vs. 0.3%
- Streptokinase vs. placebo: 0.4% vs. 0.5% (P=NS)
- Aspirin vs. placebo: 0.3% vs. 0.6%
- Streptokinase and aspirin vs. placebo: 0.3% vs. 0.6% (P=0.02)
- Streptokinase vs. placebo: 0.1% vs. 0.0% (P=0.02)
- Aspirin vs. placebo: (P=NS)
- Streptokinase and aspirin vs. placebo: 0.1% vs. 0%
TAKE AWAY: Among patients with acute MI, aspirin and streptokinase reduced 5-week vascular mortality by 20% and 23%, respectively, when compared to placebo. The combination of aspirin and streptokinase reduced the same outcome by 40%.
Reference: Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988;2(8607):349-60.