Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization - TARGET

Description:

The Do Tirofiban and ReoPro Give Similar Efficacy Trial (TARGET) was a double-blind, double-dummy, multicenter, international, prospective, randomized trial designed to compare the safety and efficacy between two glycoprotein (GP) IIb/IIIa inhibitors, tirofiban and abciximab, in the setting of percutaneous coronary revascularization.

Hypothesis:

In patients undergoing percutaneous coronary revascularization, tirofiban is not inferior to abciximab.

Study Design

Study Design:

Patients Enrolled: 5,308
Mean Follow Up: 30 days
Mean Patient Age: 62 ± 1.7
Female: 27

Patient Populations:

Patients were included if they were scheduled to undergo a coronary stenting procedure of a newly stenotic or restenotic atherosclerotic lesion in a native vessel, or a bypass graft. All lesions judged to have stenosis of more than 70% on angiography had to be amenable to stenting for the patient to qualify.

Exclusions:

Patients with cardiogenic shock, ST elevation MI, serum creatinine =2.5 mg/dl, ongoing bleeding, or a platelet count <120,000 per cubic millimeter

Primary Endpoints:

Composite endpoint of death, nonfatal MI, or urgent TVR at 30 days

Secondary Endpoints:

Secondary endpoints included each component of the composite endpoint and the effect of the study medications on prespecified subgroups (diabetics, elderly, country in which the procedure was performed, and pretreatment with clopidrogel). The endpoints of major and minor bleeding complications were defined by the TIMI trials.

Drug/Procedures Used:

Patients received the study drug intravenously immediately before revascularization. Tirofiban was given as a bolus dose of 10 µg/kg, followed by an infusion of 0.15 µg/kg/min for 18 to 24 hours. Abciximab was given as a bolus dose of 0.25 mg/kg, followed by an infusion of 0.125 µg/kg/min (maximum, 10 µg/min) for 12 hours.

Concomitant Medications:

All patients received 250 to 500 mg of aspirin before the procedure and, when possible, were to receive a loading dose of clopidrogel of 300 mg two to six hours before the procedure. Both of these antiplatelet medications were continued throughout the 30-day study period at a daily dose of 75 to 325 mg for aspirin and 75 mg for clopidrogel.

Heparin was administered at the start of the procedure at a dose of no more than 70 U/kg; the target activated clotting time (ACT) was 250 seconds. The ACT was assessed five minutes after the study drug was administered and heparin use was guided by a predefined normogram.

Principal Findings:

A total of 5,308 patients were enrolled. Of these, 4,809 patients actually received the study drug (2,398 in the tirofiban group and 2,411 in the abciximab group). The two groups were well matched regarding baseline characteristics.

Both groups received an adequate amount of the respective study drug based on mean infusion times (18.2 ± 3.9 hours for tirofiban and 11.9 ± 2.6 hours for abciximab). The median ACTs were 281 and 283 seconds, respectively.

The incidence of the primary endpoint of death, myocardial infarction (MI), or urgent target vessel revascularization (TVR) at 30 days was 7.6% in the tirofiban group and 6.0% in the abciximab group, a relative difference of 27% (p=0.038). MI occurred in 6.9% of the tirofiban group and 5.4% of the abciximab group (p=0.04).

The effects were consistent among a wide variety of subgroups, except for patients who underwent stenting for reasons other than an acute coronary syndrome. There was no significant difference in major bleeding complications; the overall rate was low (0.8%).

Tirofiban therapy was associated with a lower rate of minor bleeding (2.8% vs. 4.4%, p<0.001) and thrombocytopenia, but the rates of platelet and red-cell transfusions was similar between the two groups (0.4% vs. 0.5%, respectively).

Interpretation:

Among patients treated with percutaneous coronary revascularization, abciximab was associated with lower rates of 30-day death, MI, and urgent TVR compared with tirofiban, while the rates of major bleeding complications and the need for platelet and red-cell transfusions were similar between the two groups.

The trial was designed to assess noninferiority between the two GP IIb/IIIa inhibitors. Most of the reduction in the composite endpoint seen with abciximab was due to the lower rate of MI.

References:

Topol EJ, Moliterno DJ, Herrmann HC, et al., for the TARGET Investigators. Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med 2001;344:1888-94.

Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, ACS and Cardiac Biomarkers, Heart Failure and Cardiac Biomarkers, Interventions and ACS

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Blood Platelets, Immunoglobulin Fab Fragments, Constriction, Pathologic, Platelet Membrane Glycoprotein IIb, Tyrosine, Percutaneous Coronary Intervention, Thrombocytopenia, Platelet Glycoprotein GPIIb-IIIa Complex


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