PCI with and without Abciximab after Upstream Eptifibatide Use: Outcomes in High-Risk Patients

Figure 1. Kaplan-Meier plot to 1 year for unstable angina patients (left panel), and for myocardial infarction (MI) patients (right panel) of overall MACE-free survival (top panels), MI or death-free survival (middle panels), and for revascularization-fre
Figure 2. Risk-adjusted hazard ratios of clinical outcomes to 1 year stratified by treatment group and clinical presentation at study entry.
Figure 3. Graph depicting GP IIb/IIIa binding sites at baseline, 10 minutes after abciximab and 8 hours after abciximab (left panel); and GP IIb/IIIa receptor occupancy at baseline, 10 minutes after abciximab and 8 hours after abciximab (right panel)
PCI with and without Abciximab after Upstream Eptifibatide Use: Outcomes in High-Risk Patients
PCI with and without Abciximab after Upstream Eptifibatide Use: Outcomes in High-Risk Patients
PCI with and without Abciximab after Upstream Eptifibatide Use: Outcomes in High-Risk Patients
PCI with and without Abciximab after Upstream Eptifibatide Use: Outcomes in High-Risk Patients
PCI with and without Abciximab after Upstream Eptifibatide Use: Outcomes in High-Risk Patients
Author(s): 

Robert J. Applegate, MD, Mark A. Grabarczyk, MD, David C. Sane, MD, Matthew T. Sacrinty, MPH, Jason E. Goodin, BA, G. Sidney Statonk, MD, Talal T. Baki, MD, Sanjay K. Gandhi, MD, Michael A. Kutcher, MD, William C. Little, MD

Discussion
This observational, single-center study examined the safety and efficacy of using abciximab for high-risk patients undergoing PCI after upstream treatment with eptifibatide. We found that the incidences of bleeding and vascular complications were similar in patients who received eptifibatide as initial treatment for ACS and abciximab for PCI, compared to patients who received eptifibatide for both medical and interventional therapy. We also observed that the potential benefit of abciximab usage for PCI after upstream treatment with eptifibatide depended on the clinical presentation of the patient at the time of the index PCI.
In patients with unstable angina but no MI, the use of abciximab, chosen primarily because of high-risk lesion and procedural characteristics, appeared to be less beneficial than the use of eptifibatide alone. In patients treated with abciximab, revascularization rates were significantly higher than with eptifibatide alone, possibly reflecting the higher-risk characteristics of these patients at the time of their index PCI. In the subgroup of patients who presented with an MI within 7 days of their index PCI, the incidence of MI or death at 1 year was substantially lower in the abciximab group than in the eptifibatide-alone group, although an overall benefit in the subgroup was not observed because of a somewhat higher rate of revascularization in the abciximab group compared to the eptifibatide-alone group. These findings suggest that abciximab in unstable angina patients does not ameliorate high-risk patient or lesion characteristics that are associated with increased rates of restenosis and/or repeat revascularization. These observations, however, are also consistent with recent findings indicating that abciximab during PCI is of benefit in patients with NSTEMI,17 but not in elective cases.18
We also examined platelet function in this study and found that abciximab-mediated platelet inhibition after upstream treatment with eptifibatide was comparable to platelet inhibition achieved with abciximab alone. Platelet function has been examined after use of a second GP IIb/IIIa receptor blocker following initial treatment or use of another GP IIb/IIIa receptor blocker.19,20 In animal studies, platelet aggregability and receptor-binding studies indicated that prior exposure to eptifibatide or tirofiban did not alter the inhibition of platelet aggregability or receptor-binding of abciximab compared to the activity of abciximab alone on these indices of platelet function. In the clinical setting, Lev et al19 measured several indices of platelet function including receptor occupancy, as was done in this study, and demonstrated that receptor occupancy after administration of abciximab to patients was similar whether they had been previously exposed to tirofiban or eptifibatide compared to receptor occupancy after exposure abciximab alone. Our findings confirm the earlier results of Lev et al.
The GP IIb/IIIa inhibitors, eptifibatide and tirofiban,21,22 but not abciximab,23 have become standard treatments for patients with an ACS based on several randomized clinical trials. Moreover, both eptifibatide and abciximab have been shown to be of significant benefit in reducing adverse events following PCI, principally MIs.1–3,10,24,25 Whether one GP IIb/IIIa inhibitor is superior to another for either ACS or PCI treatment has surprisingly been evaluated in only one randomized clinical trial.5 In the TARGET study,5 abciximab was shown to be superior to tirofiban for use during PCI based on 30-day outcomes, although it is not certain that the dose of tirofiban used in the study was optimal.26,27 Whether abciximab would be superior to eptifibatide during PCI has not been examined in a randomized clinical trial, although multiple single-center experiences have been published with varying results.7,28,29 Based on a strategy of using abciximab selectively for higher-risk patients6 in a single-center observational study, we previously observed superior early outcomes with abciximab compared to eptifibatide in patients undergoing PCI.7 Since that time, however, upstream use of eptifibatide for patients with ACS has become standard practice.21,22 Moreover, data from the recent EVEREST trial,11 a randomized comparison of upstream low-dose tirofiban versus high-dose tirofiban or abciximab at the time of PCI, found that the low-dose tirofiban arm was associated with improved tissue level perfusion and attenuated myocardial damage. Whether selective use of abciximab after upstream use of GP IIb/IIIa inhibition confers additional benefit, however, has not been extensively studied.19,30
Recent studies have more clearly defined the circumstances when abciximab is beneficial during PCI. In the ISAR REACT study,18 PCI outcomes were evaluated after 600 mg of oral clopidogrel, with or without abciximab, in low- to moderate-risk patients. Abciximab did not provide additional benefit to clopidogrel in these patients, suggesting that potent antiplatelet effects are not necessary in lower-risk patients. Similarly, in the present study, in patients with upstream treatment with eptifibatide for ACS, abciximab did not confer additional benefit in patients with unstable angina but no MI. By contrast, in the ISAR-REACT 2 trial,17 abciximab use conferred additional benefits to 600 mg of clopidogrel in patients with ACS and elevated troponin undergoing PCI. These latter data, and observations from this study suggest that abciximab may have incremental benefit in the highest-risk subgroup of patients with ACS (positive cardiac markers) undergoing PCI, even with upstream treatment with eptifibatide or clopidogrel.
Study limitations. There are limitations that should be addressed. This is a single-center, observational study, and thus is subject to biases that might have affected the study outcomes. While only a carefully performed randomized trial could minimize these potential biases, the present observations reflect real-world experience. Angiographic follow up was performed for clinically indicated reasons only, thus the actual incidence of restenosis could not be assessed. Finally, this study was performed prior to the availability of drug-eluting stents. Whether similar late results would occur in the drug-eluting stent era is uncertain, but it is likely that the early results would still be relevant.

Conclusion
In this single-center, observational study of patients with ACS, the strategy of abciximab use for PCI after initial ACS treatment with eptifibatide resulted in bleeding and vascular complications that were similar to complication rates observed in patients who received eptifibatide for both treatment of ACS and PCI. In patients with unstable angina, the use of abciximab for PCI after upstream use of eptifibatide appeared less beneficial than the use of eptifibatide alone, while in the subgroup of patients with MI within 7 days of their index PCI, the incidence of MI or death at 1 year appeared lower with abciximab than with eptifibatide alone. Finally, receptor occupancy was similar after abciximab use whether or not eptifibatide was used as initial treatment. These observations are consistent with recent findings indicating that abciximab is of benefit in patients with NSTEMI, but not in lower-risk patients.

Acknowledgement. The authors acknowledge the expert secretarial assistance of Tammy Davis.


Douglassays: September 16.2011 at 09:05 am

The issue that Seems unclear to me is the use of GIIbIIIa drugs upstream in the nonPCI setting. There is abundant evidence to support it's use, FDA approved with or without PCI. And the patients often are delayed by 72 or more hours IF a procedure is anticipated (records indicate that a small % transferred to the PCI center are ultimately treated medically. My sense is that high TIMI risk NSTEMI ACS pts should receive GIIbIIIa therapy unless there is a contraindication . Comment please from those in the mainstream of current therapy. , thank you.

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