A Safety and Efficacy Study of Integrilin-Facilitated Versus Primary PCI in STEMI - ASSIST

Jul 28, 2009
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Schering-Plough Canada and Medtronic Canada
Date Published:
01/01/2009
Date Updated:
07/28/2009
Original Posted Date:
07/28/2009
References

Description:

The goal of the trial was to evaluate upfront treatment with heparin and eptifibatide compared with heparin alone among patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).

Hypothesis:

Primary PCI facilitated by eptifibatide would be more effective in preventing adverse cardiac events.

Study Design

  • Randomized
  • Parallel

Patients Screened: 1,142
Patients Enrolled: 400
Mean Follow Up: 6 months
Mean Patient Age: 60 years
Female: 19%

Patient Populations:

  • Patients with STEMI who presented within 12 hours of symptom onset

Exclusions:

  • Active bleeding or intracranial bleeding at any time
  • Stroke within 90 days
  • Major surgery or trauma within 6 weeks
  • Systolic blood pressure >200 mm Hg or diastolic blood pressure >110 mm Hg
  • Prolonged cardiopulmonary resuscitation
  • PCI within 30 days
  • Fibrinolytic or glycoprotein IIb/IIIa inhibitor within 7 days
  • Low molecular weight heparin within 12 hours
  • Coagulopathy
  • Current warfarin therapy
  • Intolerance to aspirin or clopidogrel
  • Limited life span
  • Pregnancy
  • Renal insufficiency
  • Cardiogenic shock
  • Severe contrast allergy

Primary Endpoints:

  • All-cause mortality, recurrent MI, or recurrent severe ischemia

Secondary Endpoints:

  • Individual components of the primary outcome
  • Stroke
  • TIMI major bleeding
  • TIMI minor bleeding
  • Blood transfusion

Drug/Procedures Used:

Patients with STEMI who were to undergo primary PCI were randomized to heparin plus eptifibatide (n = 201) versus heparin alone (n = 199). Eptifibatide was administered as a double-bolus 180 µg/kg (10 minutes apart), with an infusion of 2.0 µg/kg/min. Eptifibatide was supposed to be initiated prior to cardiac catheterization.

Concomitant Medications:

All patients were treated with aspirin 160 mg, clopidogrel 600 mg, and intravenous unfractionated heparin (60 U/kg to a maximum of 4000 U).

There was no difference in the use of medications between the groups. In the heparin plus eptifibatide group, at discharge, the use of aspirin was 97%, clopidogrel was 94%, beta-blocker was 93%, angiotensin-converting enzyme inhibitor was 87%, and statin was 95%.

Principal Findings:

Overall, 400 patients were randomized. There was no difference in baseline characteristics between the groups. In the heparin plus eptifibatide group, the mean age was 60 years, 19% were women, 14% had diabetes, body mass index was 28 kg/m2, eptifibatide was started 189 minutes before catheterization, time from symptom onset to balloon inflation was 196 minutes, and initial TIMI 0 or 1 flow in the culprit vessel was present in 73%. High risk, defined as age >70 years, anterior MI, or history of previous MI, was present in 57% of patients.

The primary outcome—death, MI, or recurrent ischemia at 30 days—was present in 6.5% of the heparin plus eptifibatide group versus 5.5% of the heparin alone group (p = 0.69).

At 6 months, there was no difference in adverse outcomes: death occurred in 4.6% versus 3.1% (p = 0.44), MI in 2.0% versus 1.0% (p = 0.69), severe recurrent ischemia in 4.5% versus 4.6% (p = 0.97), congestive heart failure in 7.7% versus 12.3% (p = 0.12), or stroke in 0% versus 2.0% (p = 0.06), respectively, for heparin plus eptifibatide versus heparin alone.

TIMI major bleeding occurred in 9.5% versus 5.5% (p = 0.14), TIMI major or minor bleeding in 22.4% versus 14.6% (p = 0.04), and blood transfusion in 7.5% versus 4.5% (p = 0.22), respectively, for heparin plus eptifibatide versus heparin alone.

Interpretation:

Among STEMI patients undergoing primary PCI on a background of aspirin and 600 mg of clopidogrel, the use of heparin plus upfront eptifibatide was not superior to heparin alone. Specifically, the addition of eptifibatide did not reduce the incidence of death, MI, or severe recurrent ischemia. Eptifibatide was associated with increased bleeding.

Study limitations included relatively small sample size and open-label design. The much larger EARLY-ACS trial also revealed that the upfront use of eptifibatide was not superior to placebo in the setting of non-ST-elevation acute coronary syndromes.

References:

Le May MR, Wells GA, Glover CA, et al. Primary percutaneous coronary angioplasty with and without eptifibatide in ST-segment elevation myocardial infarction. A safety and efficacy study of integrilin-facilitated versus primary percutaneous coronary intervention in ST-segment elevation myocardial infarction (ASSIST). Circ Cardiovasc Intervent 2009;Jul 22:[Epub ahead of print].

Keywords: Myocardial Infarction, Stroke, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Cardiac Catheterization, Heparin, Ticlopidine, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention, Blood Transfusion, Body Mass Index, Peptides, Heart Failure, Diabetes Mellitus


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