Clinical study
Time from symptom onset to treatment and outcomes after thrombolytic therapy

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Abstract

Objectives. This study sought to examine the relations among patient characteristics, time to thrombolysis and outcomes in the international GUSTO-I trial.

Background. Studies have shown better left ventricular function and decreased infarct size as well as increased survival with earlier thrombolysis, but the relative benefits of various thrombolytic agents with earlier administration are uncertain.

Methods. We evaluated the relations of baseline characteristics to three prospectively defined time variables: symptom onset to treatment, symptom onset to hospital arrival (presentation delay) and hospital arrival to treatment (treatment delay). We also examined the relations of delays to clinical outcomes and to the relative 30-day mortality benefit with accelerated tissue-type plasminogen activator (t-PA) versus streptokinase.

Results. Female, elderly, diabetic and hypertensive patients had longer delays at all tages. Previous infarction or bypass surgery was an additional risk factor for treatment delay. Early thrombolysis was associated with lower overall mortality rate (<2 h, 5.8%; > 4 h, 9.0%), but no additional relative benefit resulted from earlier treatment with accelerated t-PA versus streptokinase (p = 0.38). Longer presentation and treatment delays were both associated with increased mortality rate (presentation delay < 1 h, 5.6% and >4 h, 8.6%; treatment delay <1 h, 5.4%, and >90 min, 8.7%). As time to treatment increased, the incidence of recurrent ischemia or reinfarction decreased, but the rates of shock, heart failure and stroke increased.

Conclusions. Earlier treatment resulted in better outcomes, regardless of thrombolytic strategy. Elderly, female and diabetic patients were treated later, adding to their already substantial risk.

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This study was funded by grants from Bayer Corporation, New York, New York; CIBA-Corning, Medfield, Massachusetts; Genentech, Inc., South San Francisco, California, ICI Pharmaceuticals, Wilmington, Delaware; and Sanofi Pharmaceuticals, Paris, France. A complete list of the GUSTO-I investigators appears in Reference 14.