Integrilin and Tenecteplase in Acute Myocardial Infarction - INTEGRITI


The goal of the Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) trial was to evaluate the efficacy of combining eptifibatide with reduced-dose tenecteplase (TNK) in patients with ST-elevation myocardial infarction.

Study Design

Study Design:

Patients Enrolled: 438
Mean Follow Up: 30 days
Mean Patient Age: Median age 58 years
Female: 23

Patient Populations:

Ischemic discomfort ≥30 minutes with symptom onset ≤6 hours, along with ECG criteria of STEMI in patients ages 18-75 years


Uninterpretable ST-segments, active bleeding or increased risk of bleeding; previous CABG; cardiogenic shock or pulmonary edema requiring intubation; blood pressure ≥180 mm Hg systolic or ≥110 mm Hg diastolic; known hypersensitivity to any study regimen component; creatinine ≥4.0 mg/dl; other serious illness; and inability to comply with the protocol

Primary Endpoints:

Primary efficacy end point: Rate of TIMI grade 3 flow in the infarct-related artery at 60 minutes.

Primary safety end point: Rate of TIMI major hemorrhage.

Secondary Endpoints:

Corrected TIMI frame count and TMPG at 60 and 90 minutes; degree of and occurrence of complete (≥70%) ST-segment resolution at 60 and 180 minutes compared with baseline; and rates of stroke, transfusions, and thrombocytopenia

Drug/Procedures Used:

In the dose-finding phase of the trial, patients (n=189) were randomized open-label to different combinations of double-bolus eptifibatide and reduced-dose TNK. Patients in the dose confirmation were randomized 1:1 to standard-dose (0.53 mg/kg) TNK monotherapy or eptifibatide (180 µg/kg bolus, 2 µg/kg/min infusion, and 180 µg/kg bolus 10 minutes later) plus half-dose TNK (0.27 mg/kg).

Concomitant Medications:

All patients received aspirin (162 to 325 mg oral or 150 to 500 mg IV) followed by daily oral aspirin. All patients also received an unfractionated heparin bolus dose of 60 U/kg (maximum 4000 U).

Patients randomized to combination therapy received a reduced heparin infusion of 7 U/kg/h (maximum 800 U/h), and patients randomized to TNK monotherapy received the heparin infusion of 12 U/kg/h (maximum 800 U/h).

Principal Findings:

Thrombolysis in myocardial infarction (TIMI) grade 3 flow rates were similar across groups in the dose-finding phase (64% to 68%). Patency (TFG 2/3) was highest for eptifibatide 180/2/180 plus half-dose TNK (96%, p=0.02 vs. 84% for eptifibatide 180/2/90 plus half-dose TNK). In the dose confirmation phase, the eptifibatide 180/2/180 plus half-dose TNK combination compared with TNK monotherapy tended to achieve more TIMI 3 flow (59% vs. 49%, p=0.15), patency (85% vs. 77%, p=0.17), and ST-segment resolution (median 71% vs. 61%, p=0.08).

There was no difference in the median corrected TIMI frame count (35.9 vs. 40.0 frames, p=NS) or TIMI myocardial perfusion grade (TMPG) grade 3 (49% vs. 45%, p=0.59). There was a trend toward higher rates of major hemorrhage (7.6% vs. 2.5%, p=0.14) and transfusions (13.4% vs. 4.2%, p=0.02) with combination therapy.

In dose-confirmation, the composites of death or reinfarction (1.7% vs. 4.2%, p=0.25) and death, reinfarction, or urgent target vessel revascularization at 48 hours occurred less frequently with combination therapy (3.4% vs. 11.0%, p=0.02); however, these end points did not differ at 30 days.


Among patients with ST elevation MI, treatment with combination therapy of eptifibatide and half-dose TNK compared with full dose TNK monotherapy was associated with a nonsignificant trend toward higher rates of TIMI grade 3 flow, but a trend toward higher rates of major hemorrhage.

Despite angiographic data suggesting improved epicardial flow with combination therapy, the recent large, randomized GUSTO V and ASSENT 3 trials did not show a difference in mortality in ST-segment elevation MI (STEMI) patients treated with combination therapy with reduced-dose fibrinolytic and abciximab compared with full-dose fibrinolytic therapy. It has been hypothesized that the lack of mortality benefit may be due to only small improvements in epicardial flow (pooled average 6.6% across all dose confirmation phases of phase II trials), or multiple, noncardiac causes of death.

Additional trials will examine the role of combination therapy in STEMI patients undergoing facilitated percutaneous coronary intervention, as well as examining reduced-dose therapy in patients at higher risk for bleeding (age ≥75, low body weight, and female gender).


Giugliano RP, Roe MT, Harrington RA, et al. Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction. Results of the integrilin and tenecteplase in acute myocardial infarction (INTEGRITI) Phase II Angiographic trial. J Am Coll Cardiol 2003;41:1251-60.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Lipid Metabolism

Keywords: Thrombolytic Therapy, Myocardial Infarction, Platelet Aggregation Inhibitors, Peptides, Fibrinolytic Agents, Electrocardiography, Immunoglobulin Fab Fragments, Tissue Plasminogen Activator, Percutaneous Coronary Intervention

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