Time to Integrilin Therapy in Acute Myocardial Infarction - TITAN - TIMI 34

Description:

The goal of the trial was to evaluate the effect on epicardial perfusion, a strategy of early initiation of eptifibatide in the emergency department (ED), compared with a strategy of initiating eptifibatide in the cardiac catheterization laboratory among patients with ST elevation myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PCI).

Study Design

Study Design:

Patients Enrolled: 343
Mean Follow Up: 30 days
Mean Patient Age: Mean age 60 years
Female: 26

Patient Populations:

Presentation with ST elevation MI within 6 hours of symptom onset

Exclusions:

Uncontrolled hypertension, ventricular fibrillation or ventricular tachycardia requiring cardioversion, sinus bradycardia, third degree or advanced second degree heart block, new or suspected new left bundle branch block, known thrombocytopenia or severe renal insufficiency, hemorrhagic risk factors, or prior treatment with fibrinolytic or glycoprotein IIb/IIIa inhibitor within 7 days

Primary Endpoints:

Corrected TIMI frame count on diagnostic angiography

Secondary Endpoints:

TIMI flow grade on diagnostic angiography

Drug/Procedures Used:

Patients with ST elevation MI intended for primary PCI were randomized to early administration of eptifibatide in the ED (n = 174) or catheterization laboratory administration of eptifibatide following diagnostic angiography (n = 142). Eptifibatide dosing was double bolus 180 µg/kg followed by an infusion of 2.0 µg/kg/min infusion.

Concomitant Medications:

Aspirin 160-325 mg, heparin 60 U/kg bolus (maximum 4000 U), and 7 U/kg infusion (maximum 800 U/hr)

Principal Findings:

Baseline characteristics were well balanced between groups, with 17% diabetics, 45% smokers, 13% with a prior MI, and 42% with hypertension. Median time from eptifibatide bolus to diagnostic angiography was 30.5 minutes in the ED group and median time from diagnostic angiography to eptifibatide bolus was 5 minutes in the cath lab group.

The primary endpoint of corrected TIMI frame count on diagnostic angiography was lower (i.e., faster) in the ED group (77.5 frames vs. 84.3 frames, p = 0.049). TIMI grade 2 or 3 flow trended higher in the ED group (46.2% vs. 36.6%, p = 0.087), while the rate of TIMI grade 3 flow was 24.0% in the ED group and 19.0% in the cath lab group (p = 0.29). TIMI myocardial perfusion grade 3 was present more frequently in the ED group (24.3% vs. 14.2%, p = 0.026). There was no difference in post-PCI TIMI frame count (20 vs. 22 frames, p = 0.14), TIMI flow grade (87% vs. 89%, p = NS), or TIMI myocardial perfusion grade (37% vs. 37%, p = NS). However, full angiographic perfusion score (APS), which integrates pre-PCI and post-PCI epicardial and myocardial perfusion, trended better in the ED group (APS of 10-12, 21.1% vs. 12.5%, p = 0.059).

By 30 days, there was no difference in mortality (4.0% for ED group vs. 2.8% for cath lab group) and two cases of reinfarction in each group.

Congestive heart failure by hospital discharge trended lower in the ED group (2.9% vs. 7.1%, p = 0.082), but there was no difference at 30 days (4.6% vs. 7.8%, p = 0.24). TIMI major and minor bleed rates were similar between groups (6.9% vs. 7.8%, p = NS). There were no cases of intracranial hemorrhage (ICH).

Interpretation:

Among patients with ST elevation MI undergoing primary PCI, early initiation of eptifibatide in the ED was associated with faster epicardial flow and better myocardial perfusion compared with initiating eptifibatide in the cardiac catheterization laboratory.

Prior studies such as TIGER-PA and ON-TIME have examined the administration of tirofiban, another glycoprotein IIb/IIIa inhibitor, early in the ED compared with later in the cath lab, and showed similar results of improved angiographic endpoints without excess bleeding. In the present study, there were no additional bleeding complications associated with the earlier administration of eptifibatide, which was received an average of 30 minutes prior to PCI. In an exploratory analysis, longer duration of pre-PCI eptifibatide was associated with faster flow in a stepwise manner.

References:

Gibson CM, Kirtane AJ, Murphy SA, et al. Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34 trial. Am Heart J 2006;152:668-75.

Presented by Dr. C. Michael Gibson at the Texas Heart Symposium, Dallas, Texas, November 2005.

Clinical Topics: Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Acute Heart Failure, Hypertension

Keywords: Myocardial Infarction, Platelet Aggregation Inhibitors, Cardiac Catheterization, Fibrinolytic Agents, Tyrosine, Percutaneous Coronary Intervention, Intracranial Hemorrhages, Peptides, Heart Failure, Diabetes Mellitus, Hypertension, Platelet Glycoprotein GPIIb-IIIa Complex


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