November 5, 2007 (Orlando, FL) - Eptifibatide (Integrilin, Millennium Pharmaceuticals) given as a double bolus was just as effective as abciximab (ReoPro, Eli Lilly/Centocor) as an adjunct to PCI in patients with ST-elevation acute MI (STEMI) in the EVA-AMI trial, Dr Uwe Zeymer (Institute fur Herzinfarktforschung Ludwigshafen, Germany) announced here at the American Heart Association 2007 Scientific Sessions.
The late-breaking study gives some reassurances to cath labs that have already been substituting the cheaper GP IIb/IIIa inhibitor for abciximab in STEMI patients undergoing PCI, but with the anticoagulant field focusing increasingly on bleeding risk, at least one expert believes proof of equivalence for two GP IIb/IIIa inhibitors does not answer the question of whether these agents should be widely in use for STEMI patients.
EVA-AMI randomized 400 STEMI patients with less than 12 hours of symptoms to either a double bolus plus 24-hour infusion of eptifibatide or a single bolus plus 12-hour infusion of abciximab. Both therapies were used on top of aspirin, clopidogrel, and heparin or enoxaparin. As Zeymer reported today, the eptifibatide strategy was noninferior for the primary end point: ST resolution one hour post-PCI. In fact, the proportion of patients with no ST resolution after 60 minutes was statistically lower in the eptifibatide arm (14.7% vs 5.4%, p=0.021). In-hospital events, including death, reinfarction, heart failure, target vessel revascularization (TVR), and CABG, were similar between the two groups; major and minor bleeding rates were also nonsignificantly different between the two GP-IIb/IIIa-inhibitor strategies.
|End point||Abciximab (%)||Eptifibatide (%)|
Currently, the ACC/AHA guidelines give a class 2a recommendation for the use of abciximab in primary PCI, but only a class 2b recommendation for tirofiban and eptifibatide. According to Zeymer, the EVA-AMI study is the first to show that a small-molecule GP IIb/IIIa inhibitor is as effective as abciximab in the setting of PCI for STEMI. "Since this drug is less expensive, it might be more useful in clinical practice and the guidelines might be changed," he said. In Europe, he noted, eptifibatide is by far the cheapest option, at about US$300 per patient; by way of comparison, abciximab costs about $1500 per patients, while bivalirudin costs about $600 per patient.
To heart wire , however, Zeymer acknowledged that the "obvious question" is what the future role of GP IIb/IIIa inhibitors will be in the wake of the HORIZONS study of bivalirudin, presented earlier this month at the TCT meeting. Zeymer believes that despite the benefits of bivalirudin in reducing bleeding rates, GP IIb/IIIa inhibitors will continue to play a role in patients who have a higher risk of ischemic events. In his own practice, Zeymer says he and his colleagues use both of the GP-IIb/IIIa-inhibitor strategies studied in EVA-AMI.
Not enough data for GP IIb/IIIa inhibitors to beginwith?
Commenting on the study for heart wire , Dr Marc Cohen (Beth Israel Medical Center, Newark, NJ) called the results "great," with the caveat that the numbers were small.
But Cohen estimates that despite modest data on GP IIb/IIIa inhibitors in STEMI, approximately 60% of interventionalists use GP IIb/IIIa inhibition in patients undergoing PCI for STEMI, and of these, more than one-third are already "comfortable" using eptifibatide, extrapolating from the non-STEMI trials.
"There is a very, very broad geographic variability here. . . . In general, in Europe, there is a very modest uptake of GP IIb/IIIa inhibitors, for STEMI, non-STEMI, any which way. In the US, there is a more substantial update of GP IIb/IIIa inhibitors, including in STEMI: a lot of us feel this is the big kahuna, this is where all the thrombus is. So while we may not be, day after day, big GP IIb/IIIa inhibitor users, for our routine cases, a fair number of interventionalists like myself almost automatically use GP IIb/IIIa inhibitors in our STEMI cases."
Results from EVA-AMI, Cohen says, suggest that there is equivalent efficacy and safety. While bleeding rates were numerically higher with eptifibatide, Cohen points out that the trial used a 24-hour infusion rather than the standard 18-hour infusion, which may have contributed to the slightly higher major bleeding rate.
But, also commenting on the study, Dr Ron Waksman (Washington Hospital, DC) was less impressed with the results, stating that a class effect for the GP IIb/IIIa inhibitors makes it impossible in a trial of this size to show any meaningful differences between eptifibatide and abciximab. "This study is underpowered to show any differences between the safety and efficacy of these two drugs, that's the main thing," he said. "It does show that both of them are associated with similar bleeding and similar results, but the issue is, there are not enough data to support the use of GP IIb/IIIa inhibitors in acute MI to begin with."
Waksman emphasizes that the whole field of anticoagulant research has shifted: bleeding risk has become the "most important thing" in PCI--a view reinforced by today's release of the TRITON-TIMI 38 study. "We need to rethink anything that seems to cause bleeding, including GP IIb/IIIa inhibitors in the setting of AMI," he suggested. "The question is not whether to use ReoPro or Integrelin, it's whether to use a GP IIb/IIIa inhibitor at all. There is an increase in bleeding when you use them; there is a price for it."
Zeymer disclosed receiving speaker's honoraria and research support from GlaxoSmithKline and Eli Lilly. Cohen has previously disclosed receiving honoraria and or consulting fees from Sanofi-Aventis, Bristol-Myers Squibb, Merck, Schering-Plough, and The Medicines Company.
Heartwire from Medscape © 2007 Medscape
Cite this: Shelley Wood. EVA-AMI: Eptifibatide Equal to Abciximab for STEMI Patients Undergoing PCI - Medscape - Nov 05, 2007.