Copyright © 2003 by the European Society of Cardiology.
Clinical research
Risk of intracranial haemorrhage with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy in acute myocardial infarction
Dichotomous response as a function of age in the GUSTO V trial
a Department of Cardiology, Niguarda Hospital, Milan, Italy
b Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
c Department of Cardiology, Cleveland Clinic, Cleveland, Ohio, USA
d Department of Neurology, Cleveland Clinic, Cleveland, Ohio, USA
e Department of Cardiology, Ospedale SS Annunziata, Sassari, Italy
f Department of Cardiology, Presidio Ospedaliero Ca’ Foncello, Treviso, Italy
g Department of Cardiology, Green Lane Hospital, Auckland, New Zealand
h Division of Cardiology, Ospedali Riuniti di Parma, Parma, Italy
i Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
* Correspondence to: Dr. Stefano Savonitto, Prima Divisione di Cardiologia, Ospedale Niguarda Ca’ Granda, Piazza Ospedale Maggiore 3, 20162 Milano, Italy. Tel: +39-335-6056565; Fax: +39-02-6883804
E-mail address: stefano.savonitto{at}fastwebnet.it
Received 10 April 2003; revised 5 June 2003; accepted 17 July 2003
Abstract
Background Intracranial haemorrhage is an important limitation to pharmacologic reperfusion therapy for acute myocardial infarction. The combination of a glycoprotein IIb/IIIa inhibitor, half-dose plasminogen activator and reduced-dose heparin has been evaluated as an alternative to standard fibrinolytic therapy in this setting.
Methods and results We evaluated the relation between univariate and multivariate predictors of intracranial haemorrhage and the effect of treatment with either reteplase alone (10U bolus twice, 30min apart) with standard-dose heparin (5000U bolus followed by an infusion of 1000Uh–1for patients 
80kg and 800Uh–1for those <80kg) or combination therapy with abciximab (0.25mg/kg bolus and 0.125µg/kg/min for 12h) and half-dose reteplase (two boluses of 5U 30min apart) with reduced-dose heparin (60Ukg–1bolus, maximum 5000U, followed by an infusion of 7Ukg–1h–1) in the 16 588 patients randomized in the GUSTO V trial. Overall, the incidence of intracranial haemorrhage was similar in the two groups (0.6% vs 0.6%; OR 1.05, 95% CI 0.71, 1.56). The median (25th–75th) time from drug administration to intracranial haemorrhage was 5.5 (3.4–11) hours with combination therapy and 9.2 (5.9–22) hours with reteplase (P=0.048). Among the multivariable predictors of intracranial haemorrhage, only age showed a significant interaction with treatment effect (age per treatment interaction chi-square 4.60, P=0.032) with a lower risk of combination therapy for younger patients and a higher risk for the elderly.
Conclusions Although no additional risk of intracranial haemorrhage has been observed with combination therapy in the whole population, a significant age pertreatment interaction exists, with a lower risk with combination therapy in younger patients, and a higher risk in the elderly.
Key Words: Fibrinolysis • Stroke • Myocardial infarction • Heparin • Abciximab
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