The GUSTO V Randomised Trial - GUSTO V

Description:

Reperfusion Therapy for Acute Myocardial Infarction With Fibrinolytic Therapy or Combination Reduced Fibrinolytic Therapy and Platelet Glycoprotein IIb/IIIa Inhibition: The GUSTO V Randomised Trial.

Hypothesis:

Is the combination of half-dose reteplase and abciximab superior, or not inferior, to reteplase alone for 30-day mortality in patients with ST elevation acute myocardial infarction (STEMI)?

Study Design

Study Design:

Patients Enrolled: 16588

Primary Endpoints:

30 day mortality

Drug/Procedures Used:

A total of 16,588 patients within the first 6 hours of STEMI were randomized to receive standard dose reteplase (two 10 U boluses 30 minutes apart, n=8260) or half dose reteplase (two boluses of 5 U, 30 minutes apart) plus full-dose abciximab (0.25 mg/kg bolus and 0.125μ/kg/min [maximum 10μ/min], n=8328). Analysis was by intention to treat for primary (30-day mortality) and secondary (various complications of STEMI) end points.

Principal Findings:

The 30-day mortality in the standard-dose reteplase and half-dose reteplase plus abciximab was similar (5.9% vs. 5.6%, odds ratio [OR] 0.95, confidence interval [CI] 0.83-1.08, p=0.43). The composite of death or nonfatal reinfarction was lower for the combination than for reteplase alone (OR 0.83, CI 0.74-0.93, p=0.0011). The recurrent MIs were mostly made up of ischmemic ST segment changes as determined by the unblinded investigator. The need for urgent revascularization was lower for the combination therapy. Contrariwise, non-intracranial bleeding complications occurred with greater frequency in the combination group (severe or moderate bleeding OR 2.03, CI 1.70-2.42; p<0.0001). While overall rates of ICH were the same between the 2 regimens, the rate of ICH in patients over the age of 75 was increased in the combination therapy arm (2.1% vs 1.1%, p<0.05 for the interaction term).

For patients with STEMI, combined reteplase and abciximab was non-inferior (although not superior) to standard reteplase for decreasing the 30-day mortality. The beneficial effects of combination therapy over standard reteplase on secondary complications, were partially offset by a doubling of the rate of non-intracranial bleeding with this regimen, and by a higher risk of ICH in patients over the age of 75.

Interpretation:

This trial validates the non-inferiority of an alternative regimen of a thrombolytic agent (reteplase) plus glycoprotein IIbIIIa antagonist (abciximab) vs. standard reteplase therapy. Future subgroup analysis of this trial data may provide further insights into identifying subgroups that might benefit most and those that would be at an increased risk of adverse side effects, particularly bleeding with the use of the combination therapy.

References:

1. Lancet 2001;357:1905-14.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Lipid Metabolism

Keywords: Thrombolytic Therapy, Myocardial Infarction, Intention to Treat Analysis, Recombinant Proteins, Fibrinolytic Agents, Immunoglobulin Fab Fragments, Tissue Plasminogen Activator, Platelet Membrane Glycoproteins, Platelet Glycoprotein GPIIb-IIIa Complex


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