Eptifibatide Versus Abciximab in Primary PCI for Acute Myocardial Infarction - EVA-AMI

Jul 26, 2010
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
GlaxoSmithKline
Date Presented:
01/01/2007
Date Published:
01/01/2010
Date Updated:
07/26/2010
Original Posted Date:
07/26/2010
References

Description:

The goal of the trial was to evaluate use of abciximab compared with eptifibatide among patients undergoing primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI).

Hypothesis:

Eptifibatide would be noninferior to abciximab in achieving complete ST-segment resolution at 60 minutes after PCI in patients presenting with STEMI.

Study Design

  • Randomized

Patients Enrolled: 427
Mean Follow Up: 6 months
Mean Patient Age: 61 years
Female: 22%

Patient Populations:

  • STEMI within 12 hours of symptom onset scheduled for primary PCI
  • Age >18 years

Exclusions:

  • Left bundle branch block
  • Fibrinolytic therapy within prior 24 hours
  • Oral anticoagulant with an international normalized ratio >2
  • Known platelet count <100,000/mm3, or known hemorrhagic diathesis
  • Stroke or transient ischemic attack within 30 days in the past 6 months or any permanent residual neurological defect
  • Evidence of an active gastrointestinal or urogenital bleeding
  • Major surgery within 6 weeks
  • History of allergic reaction to abciximab or eptifibatide or any component used in the study (including contrast media)
  • Known severe renal (creatinine clearance <30 ml/min) or hepatic insufficiency
  • Severe concomitant disease with life expectancy <1 year
  • Participation in any study using an investigational drug or device within 30 days or within 5 half-lives of the investigational drug (whichever was longer) of entry into this study
  • Inaccessibility due to geographic or social factors during treatment or follow-up

Primary Endpoints:

  • ST resolution at 1 hour post-PCI, evaluated for noninferiority

Secondary Endpoints:

  • Other ECG measures of myocardial perfusion
  • Angiographic assessements of patency of the infarct-related artery
  • Death, reinfarction, target vessel revascularization, and bleeding events through 30 days

Drug/Procedures Used:

Patients with STEMI scheduled for primary PCI were randomized to glycoprotein IIb/IIIa inhibition with either eptifibatide (double bolus of 180 mcg/kg followed by 24-hour infusion of 2 mcg/kg/min; n = 226) or abciximab (0.25 mg/kg bolus followed by 12-hour infusion of 0.125 mcg/kg/min; n = 201). Electrocardiograms (ECGs) were performed at baseline and 1 hour post-PCI to evaluate ST resolution.

Concomitant Medications:

Aspirin (96%), clopidogrel (99%), unfractionated heparin (62%), low molecular weight heparin (70%), beta-blockers (89.5%), and statins (89%)

Principal Findings:

Median time from symptom onset to treatment with study drug was approximately 230 minutes, and time from start of study drug to PCI was 30 minutes. Left anterior descending was the infarct-related vessel in 44% of the population, with about 10% with Killip class >I on presentation. Baseline Thrombolysis in Myocardial Infarction (TIMI) flow grade was 0 or 1 in about 61% of the patients. About 95% of the study patients underwent PCI, with direct stenting in about 64% of the patients, and 18% undergoing thrombectomy. Complete ST resolution, defined as >70% resolution, was noted in 12% of the patients prior to PCI.

Post-PCI TIMI flow grade 3 did not differ between treatment groups (82.0% with eptifibatide vs. 84.0% with abciximab, p = NS). Complete ST resolution 60 minutes after PCI was present in 62.6% of the eptifibatide group and 56.3% of the abciximab group (intention-to-treat analysis), meeting the criteria for noninferiority.

Among the in-hospital clinical events, there was no difference in deaths (3.5% in each group), MI (0% vs. 1.5%), or target vessel revascularization (2.2% vs. 4%) for eptifibatide versus abciximab, respectively. TIMI major bleeding occurred in 4.0% of the eptifibatide group and 2.0% of the abciximab group (p = 0.27). There was also no difference in TIMI minor bleeding (12.4% vs. 9.0%, p = 0.24). Thirty-day mortality was similar (5.8% vs. 3.5%, p = 0.36), although recurrent MI tended to be lower in the eptifibatide arm (0% vs. 2.5%, p = 0.02). This was true at 6-month follow-up as well (0.4% vs. 3.5%, p = 0.03), although mortality rates (6.2% vs. 4.5%) were still similar.

Interpretation:

Among patients undergoing primary PCI for STEMI, glycoprotein IIb/IIIa inhibition with eptifibatide was noninferior to abciximab with respect to the primary endpoint of complete ST resolution at 1 hour post-PCI.

Prior studies have shown that complete ST resolution is related to reduced mortality in STEMI. In the present study, this surrogate endpoint demonstrated noninferiority between these two agents. What impact the findings of this surrogate endpoint would have on clinical events is not known given the very small sample size of the trial. While bleeding rates overall were low and did not differ between treatment groups, a larger study would be needed to fully compare the safety profile of these glycoprotein IIb/IIIa inhibitors in the setting of primary PCI for STEMI.

References:

Zeymer U, Margenet A, Haude M, et al. Randomized comparison of eptifibatide versus abciximab in primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction: results of the EVA-AMI trial. J Am Coll Cardiol 2010;56:463-469.

Presented by Dr. Uwe Zeymer at the American Heart Association Annual Scientific Session, Orlando, FL, November 2007.

Keywords: Myocardial Infarction, Follow-Up Studies, Platelet Aggregation Inhibitors, Biomarkers, Thrombectomy, Peptides, Electrocardiography, Immunoglobulin Fab Fragments, Percutaneous Coronary Intervention, Platelet Glycoprotein GPIIb-IIIa Complex


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