Clinical Question

In patients with acute myocardial infarction undergoing thrombolytic therapy, which regimen improves survival: streptokinase with subcutaneous heparin, streptokinase with intravenous heparin, accelerated tissue plasminogen activator (t-PA) with intravenous heparin, or a combination of streptokinase plus t-PA with intravenous heparin?

Bottom Line

In patients with acute myocardial infarction, accelerated t-PA combined with intravenous heparin provided a survival benefit over standard thrombolytic regimens with streptokinase.

Major Points

Guidelines

Design

- Multicenter, randomized, open-label trial
- N=41,021
- Four treatment groups:
1. Streptokinase with subcutaneous heparin
2. Streptokinase with intravenous heparin
3. Accelerated t-PA with intravenous heparin
4. Combination streptokinase plus t-PA with intravenous heparin
- Setting: 1081 hospitals in 15 countries
- Enrollment: December 1990 to February 1993

Population

- Patients with symptoms of myocardial infarction of less than 6 hours' duration with ST-segment elevation

Interventions

- Streptokinase (1.5 million U) with either subcutaneous or intravenous heparin, or
- Accelerated t-PA with intravenous heparin, or
- Combined streptokinase plus t-PA with intravenous heparin

Outcomes

- Primary: 30-day mortality
- Secondary: Combined endpoints of death and nonfatal stroke, death and nonfatal hemorrhagic stroke, and death and nonfatal disabling stroke
- Tertiary: Stroke and bleeding complications

Criticisms

- Open-label design without a placebo group may introduce bias
- The cost and complexity of administering t-PA may limit its widespread use

Funding

- Supported by a combined grant from Bayer, CIBA-Corning, Genentech, ICI Pharmaceuticals, and Sanofi Pharmaceuticals

Further Reading

The full article, as published in The New England Journal of Medicine, provides a detailed account of the study methods, populations, interventions, and outcomes.