Eptifibatide started in the ED improves blood flow, myocardial perfusion

Shelley Wood

November 13, 2005

Dallas, TX - Patients heading to PCI with acute ST-segment elevation MI (STEMI) who receive early initiation of eptifibatide (Integrilin, Schering Corp) in the emergency department (ED) instead of in the angioplasty suite have improved TIMI blood flow and superior myocardial perfusion, new study results show.

Dr C Michael Gibson

The Time to Integrilin Therapy in Acute Myocardial Infarction—Thrombolysis in Myocardial Infarction (TITAN-TIMI 34) results were presented by Dr C Michael Gibson (Brigham and Women's Hospital, Boston, MA) during a Texas Heart Institute-sponsored satellite session before the official start of the American Heart Association Scientific Sessions 2005.

"Among patients who are to undergo primary PCI for STEMI, GP IIb/IIIa inhibition should be initiated as soon as possible prior to cardiac catheterization," Gibson stated.

TITAN-TIMI 34 randomized 343 patients undergoing primary PCI for acute STEMI to eptifibatide initiated in either the emergency department or the catheterization laboratory. The primary end point of the study was corrected TIMI frame count (CTFC), while the secondary end point was myocardial perfusion.

As Gibson showed during the satellite session, blood flow was increased significantly in the emergency-department group, compared with those treated immediately before PCI. Myocardial perfusion was likewise improved in the ED-treated patients. Rates of major and minor bleeding, as well as stroke, intracranial hemorrhage, need for transfusion, or thrombocytopenia, were not significantly different between the two groups.

TITAN-TIMI 34 outcomes

End point ED-treated patients Cath-lab-treated patients p
CTFC increase from baseline (frames, n) 77.5 84.3 0.049
Myocardial perfusion* (%) 24.3 14.2 0.026
*Proportion of patients with normal TIMI myocardial-perfusion grade

In an interview with heartwire , Gibson agreed that while definitive answers could come only from outcomes data in larger studies, an analysis at five days after PCI or hospital discharge showed no differences in death or MI, but a "provocative trend" toward reduced heart failure in the emergency-department-treated patients (2.9%) compared with 7.1% in the cath-lab-treated patients (p=0.082).

Of note, the effect of eptifibatide appeared strongest in patients who had received the drug the soonest, suggesting a time-dependent improvement in flow. The findings were striking, given that the door-to-angiography time in TITAN-TIMI 34 was only 30 minutes, on average.

"Time is muscle," Gibson told heartwire . "Every improvement we can make in opening arteries counts. And the earlier someone starts on the drug, the better the flow."

An important first step

Dr William O'Neill

Commenting on the study for heartwire , Dr William O'Neill (Beaumont Hospital, Royal Oak, MI) pointed out that eptifibatide is in fact already approved for emergency-room use (specifically indicated for patients with unstable angina/non-ST-segment-elevation MI), but that it is being sidelined to some extent by competing agents. In particular, cath labs have witnessed a move toward dropping GP IIb/IIIa inhibition in favor of high doses of upfront clopidogrel combined with unfractionated heparin. TITAN-TIMI 34, O'Neill said, was the manufacturer's attempt to evaluate an improved strategy that could counter the increased use of clopidogrel without first conducting a large outcomes trial.

"What the eptifibatide folks are worried about is that people are going to start just using clopidogrel; so this is the first step toward showing that there might be some advantage [to using eptifibatide earlier]. They didn't want to do a large, multicenter trial with hundreds of patients before they had some signal that this was a beneficial strategy. So the importance of this trial is that it is a signal there might be some improvement in TIMI flow and it may have a salutary effect in the artery with treatment started in the ED."

That said, O'Neill continued, "This isn't going to change practice. This was basically just a pilot study and what they're going to need to do is a study of heparin and high-dose clopidogrel vs eptifibatide in the ER. That's the direction people are headed right now."

AstraZeneca, Boston Scientific, Cordis Endovascular, Eli Lilly, Medtronic, Merck, Sanofi-Aventis, and Schering-Plough all provided grant support for the Texas Heart Institute-sponsored symposium.


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