Fast track — ArticlesReperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial
Introduction
Reperfusion therapy for acute myocardial infarction became the standard of care in the late 1980s,1, 2 and although there have been improvements in fibrinolytic therapy,3, 4, 5 pharmacological treatment has many limitations. Compared with standard plasminogen-activator therapy, several pilot studies that combined low-dose plasminogen activator and platelet glycoprotein IIb/IIIa antagonists have suggested better speed, durability, and completeness of myocardial reperfusion.6, 7, 8 To provide a meaningful assessment of combined therapy, a large-scale trial was necessary. GUSTO V was powered to detect a mortality difference between standard fibrinolytic therapy and the combination of reduced dose fibrinolytic and a IIb/IIIa receptor antagonist. Our aim was to find out whether the combination of half-dose reteplase and abciximab would be superior, or not inferior, to reteplase alone for mortality at 30 days after enrolment. Secondary endpoints included the composite of death and non-fatal disabling stroke, reinfarction, recurrent ischaemia, urgent revascularisation, intracranial haemorrhage and non-intracranial bleeding complications, and mortality at 1 year.
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Patients
820 hospitals in 20 countries participated in the trial, and the protocol was approved by each centre's institutional review board. Each patient provided informed consent to participate. The inclusion criteria were: continuous symptoms of chest discomfort for at least 30 min and fewer than 6 h from onset to the time of randomisation, along with electrocardiographic criteria of ST-elevation myocardial infarction or new left-bundle branch block.3, 4, 5 Exclusion criteria were: age less than 18
Results
16 588 patients were enrolled from July 7, 1999, until February 16, 2001 (figure 1). Table 1 shows the demographic characteristics of the two treatment groups. 1088 (13–2%) of the patients assigned reteplase and 1149 (13–8%) of those assigned reteplase and abciximab were older than 75 years. The use of conjunctive medications did not differ between the groups–at discharge, 6327 (77%) of those on reteplase and 6388 (77%) of those on reteplase and abciximab were receiving (3-blockade; 4640 (56%)
Discussion
Since fibrinolytic therapy became the standard of care for acute myocardial infarction in the 1980s, limitations have been recognised, including the relatively late time taken to re-establishing coronary blood, clinical instability with respect to recurrent ischaemia and reocclusion, and the lack of reperfusion at the myocardial tissue level in a large proportion of patients.13, 14, 15 One of the obstacles to more effective reperfusion has been the known pivotal effect of platelets in
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