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

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 (10 U bolus twice, 30 min apart) with standard-dose heparin (5000 U bolus followed by an infusion of 1000 U h(-1) for patients greater than or equal to80 kg and 800 U h(-1) for those <80 kg) or combination therapy with abciximab (0.25 mg/kg bolus and 0.125 mug/kg/min for 12 h) and half-dose reteplase (two boluses of 5 U 30 min apart) with reduced-dose heparin (60 U kg(-1) bolus, maximum 5000 U, followed by an infusion of 7 U kg(-1) h(-1)) in the 16588 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 per treatment interaction exists, with a lower risk with combination therapy in younger patients, and a higher risk in the elderly. (C) 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.