The goal of the study was to evaluate if a combined reperfusion regimen with the platelet glycoprotein (GP) IIb/IIIa inhibitor tirofiban provides additional benefit in optimal myocardial reperfusion of patients with a ST-elevation acute myocardial infarction (AMI).

Study Design

Study Design:

Patients Enrolled: 144
Mean Follow Up: 30 days
Mean Patient Age: Mean age 59.6 years
Female: 20

Patient Populations:

Age >18 years; presentation with an AMI, defined as typical chest pain lasting >30 minutes within the previous six hours, with a clear ST-segment elevation of >0.1 mV in ≥2 contiguous electrocardiographic leads; and candidate for either fibrinolytic therapy or PCI. For patients assigned to PCI, inclusion criteria also included native coronary artery lesion ≤40 mm, with a reference diameter ≤2.5 mm.


Usual contraindications for fibrinolytic therapy; previous AMI; cocaine or amphetamine-induced MI; history of left ventricular dysfunction or multiple and advanced coronary artery disease; valvular disease with significant hemodynamic repercussions; cancer; advanced renal, pulmonary, or liver failure; previous coronary surgical revascularization; left bundle branch block; cardiogenic shock at entry; pulmonary edema requiring mechanical support; intolerance to aspirin or heparin or use of heparin 24 hours before randomization; and incapacity to provide written informed consent. For patients assigned to PCI, exclusion criteria also included coronary lesions that were anatomically inadequate for intervention or those in which a multivessel procedure was required.

Primary Endpoints:

TIMI flow grade 3 in the infarct-related coronary 90 minutes after lytic administration

Secondary Endpoints:

TIMI flow grade 2/3 in the infarct-related coronary 90 minutes after lytic administration; TMP rates; and time to first event of a composite index of major cardiovascular events, including death, reinfarction, stroke (hemorrhagic or nonhemorrhagic), need for percutaneous or surgical coronary revascularization, development of heart failure, new episodes of refractory ischemia, or severe ischemic-related hemodynamic instability

Drug/Procedures Used:

Patients were randomized to either a conjunctive strategy with tirofiban or a standard strategy, and were then randomized again to either lytic therapy or percutaneous coronary intervention (PCI). The four randomization arms were: 1) a conjunctive strategy with tirofiban (4 µg/kg/min/30-minute bolus; infusion of 0.1 µg/kg/min) plus low-dose alteplase (50 mg); 2) a conjunctive strategy with tirofiban plus stenting PCI; 3) a standard strategy plus full-dose alteplase (100 mg); or 4) a standard strategy plus stenting PCI. Patients underwent angiography 90 minutes following thrombolytic administration (for the lytic group) or PCI within 90 minutes of tirofiban administration (for the PCI group). Angiographic films were analyzed by a central core laboratory.

Concomitant Medications:

Aspirin 300 mg and intravenous heparin bolus of 50 U/kg followed by maintenance infusion of 10 U/kg/h titrated to activated partial thromboplastin time of 60-75 seconds

Principal Findings:

The primary endpoint of thrombolysis in myocardial infarction (TIMI) grade 3 flow at 90 minutes was higher in the conjunctive group compared with the standard group (79% vs. 61%, relative risk [RR] 2.43, p=0.019), as was TIMI myocardial perfusion (TMP) grade 3 (56% vs. 39%, RR 1.96, p=0.045). Compared with the full dose of alteplase alone, the conjunctive reperfusion regimen of low-dose alteplase and tirofiban was associated with higher rates of both TIMI 3 flow (66% vs. 42%, p=0.03) and TIMI 2/3 flow (58% vs. 75%, p=0.02). In both the PCI and lytic groups individually, TMP grade 3 trended to occur more frequently in the conjunctive group versus the standard care group (44.4% vs. 25%, p=0.08 in the lytic groups; 67% vs. 53%, p=0.16 in the PCI groups).

The composite clinical endpoint of death/MI/reinfarction (RI)/revascularization/congestive heart failure/stroke at 30 days was lower in the conjunctive group versus the standard group (19% vs. 39%, RR 0.54, p=0.036). The composite clinical endpoint of death/MI/RI was also lower in the conjunctive group (3% vs. 14%, RR 0.17, p=0.023).

The composite clinical endpoint trended lower in the conjunctive group versus the standard group in the lytic therapy group (39% vs. 58%, p=0.14) as well as the PCI group (11% vs. 28%, p=0.09). Likewise, the composite clinical endpoint of death/MI/RI trended lower in the conjunctive group versus the standard group in the lytic therapy group (0.3% vs. 14%, p=0.11) as well as the PCI group (0.3% vs. 14%, p=0.11).

There was no difference in bleeding events between conjunctive and standard groups (8.0% for standard group plus lytic, 8.0% for standard group plus PCI, 6.0% for conjunctive plus lytic, and 11.0% for conjunctive plus PCI).


Among patients with ST-elevation AMI, conjunctive treatment with the GP IIb/IIIa inhibitor tirofiban, along with either low-dose lytic or PCI, was associated with higher rates of TIMI grade 3 flow and TMP grade 3 at 90 minutes compared with treatment with lytic or PCI alone. Unlike other trials of combination therapy with GP IIb/IIIa inhibitors such as GUSTO V, there was no increased bleeding in the combination therapy arms. It should be emphasized, however, that the sample sizes were samll. Additionally, while the overall sample size of the study was small, there were fewer clinical events in the combination therapy arms.


Martinez-Rios MA, Rosas M, Gonzalez H, et al. Comparison of reperfusion regimens with or without tirofiban in ST-elevation acute myocardial infarction. Am J Cardiol 2004;93:280-7.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Lipid Metabolism, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Risk, Myocardial Infarction, Stroke, Platelet Aggregation Inhibitors, Coronary Disease, Fibrinolytic Agents, Tyrosine, Platelet Membrane Glycoprotein IIb, Percutaneous Coronary Intervention, Pharmaceutical Preparations, Heart Failure, Tissue Plasminogen Activator, Myocardial Reperfusion, Platelet Glycoprotein GPIIb-IIIa Complex

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