MOA
PK & PD Properties
Efficacy
Efficacy Introduction
Risk Reduction Pre-PCI
Myocardial Perfusion
Long-term Risk Reduction Post-PCI
Dosing Administration
Dosing Guidelines & Cockcroft-Gault Equation
Ease of Administration
Bolus Delivery
Infusion Delivery
Dosing Compatibilities
Safety
Major Bleeding in PCI
Minor Bleeding in PCI
Bleeding Rates in PROTECT
Bleeding in Renally Impaired Patients
Clinical Studies Database
PURSUIT
ESPRIT
PROTECT
CLEAR PLATELETS
Clear Platelets Introduction
Platelet Aggregation Inhibition
Reduction of Troponin-I Release
Full Prescribing Information
Request More Information

Enhanced Suppression of the Platelet IIb/IIIa Receptor with
INTEGRILIN® Therapy (ESPRIT)1

Objective

To assess whether pretreatment with INTEGRILIN® improves clinical outcomes in patients undergoing coronary stent intervention.

Design

Multi-center, double-blind, randomized, placebo-controlled study that enrolled 2,064 patients undergoing elective or urgent PCI with intended intracoronary stent placement.

INTEGRILIN® & Comparator Doses

Patients were randomized to:
  • Placebo (aspirin + heparin + clopidogrel)
  • INTEGRILIN® + aspirin + heparin + clopidogrel*

Results

INTEGRILIN® significantly reduced the primary endpoint (composite of death, MI, urgent target vessel revascularization [UTVR] and thrombotic bailout † at 48 hours) and the key secondary endpoint (composite of death, MI, or UTVR at 30 days).
  • The primary endpoint was reduced 37% (10.5% with placebo vs 6.6% with INTEGRILIN®; P=0.0015)
  • The key 30-day secondary endpoint was also reduced (10.5% with placebo vs 6.8% with INTEGRILIN® (P=0.0034)
  • INTEGRILIN® reduced the occurrence of MI at 48 hours from 9% for placebo to 5.4%
    (P=0.0015) and maintained that effect with significance at 30 days
  • Significant event reductions with INTEGRILIN® were maintained through 1 year2
  • Major bleeding with INTEGRILIN® was 1.3% vs 0.4% with placebo; P=0.027
  • Minor bleeding with INTEGRILIN® was 3.0% vs 2.0% with placebo
* INTEGRILIN® 180-mcg/kg IV bolus, followed immediately by a continuous infusion of 2-mcg/kg/min, with a second bolus of 180 mcg/kg administered 10 minutes later. INTEGRILIN® infusion was continued for 18 to 24 hours after PCI or until hospital discharge, whichever came first. Each patient received at least one dose of aspirin (162 to 325 mg) and 60 U/kg of heparin as a bolus (not to exceed 6000 Units) if not already receiving a heparin infusion. Additional boluses of heparin (10 to 40 U/kg) could be administered in order to reach a target ACT between 200 and 300 seconds.
† Bailout was to open-label INTEGRILIN® due to a thrombotic complication of PCI (eg, visible thrombus, “no reflow,” or abrupt closure) at 48 hours.
 

IMPORTANT PRESCRIBING AND SAFETY CONSIDERATIONS

Indications for INTEGRILIN® (eptifibatide) Injection:
  • For the treatment of patients with acute coronary syndrome (UA/NSTEMI), including patients who are
    to be managed medically and those undergoing percutaneous coronary intervention (PCI)
  • For the treatment of patients undergoing percutaneous coronary intervention (PCI), including those
    undergoing intracoronary stenting
Contraindicated in Patients With:
  • A history of bleeding diathesis or evidence of active abnormal bleeding within the previous 30 days
  • Severe hypertension (systolic blood pressure >200 mm Hg or diastolic blood pressure >110 mm Hg) not adequately
    controlled on antihypertensive therapy
  • Major surgery within preceding 6 weeks
  • History of stroke within 30 days or any history of hemorrhagic stroke
  • Current or planned administration of another parenteral GP IIb-IIIa inhibitor
  • Dependency on renal dialysis
  • Known hypersensitivity to any component of the product
Precautions and Warnings:
  • In patients undergoing PCI, INTEGRILIN® (eptifibatide) Injection is associated with an increase in major and minor bleeding at the site of arterial sheath placement. Special care should be employed to minimize the risk of bleeding among these patients
  • If bleeding cannot be controlled with pressure, infusion of INTEGRILIN® and concomitant heparin should be stopped immediately
  • Because INTEGRILIN® inhibits platelet aggregation, caution should be employed when it is used with drugs that affect hemostasis, including thrombolytics, oral anticoagulants, NSAIDs, and dipyridamole
  • Use with other GP IIb-IIIa inhibitors should be avoided
  • INTEGRILIN® is cleared in part by the kidney and its plasma concentrations are doubled in patients with renal disease (creatinine clearance
    <50 mL/min). Therefore, the infusion dose of INTEGRILIN® needs to be reduced to 1 mcg/kg/min in these patients. INTEGRILIN® is contraindicated in patients who are dependent upon renal dialysis (please see dosing guidelines)
  • Caution should be exercised when administering eptifibatide to patients with a platelet count <100,000/mm3
  • Bleeding is the most common complication encountered during INTEGRILIN® therapy. The majority of excess major bleeding events were localized at the femoral artery access site. Oropharyngeal, genitourinary, gastrointestinal, and retroperitoneal bleeding were seen more commonly with INTEGRILIN® compared with placebo.

For full Prescribing Information, click here. (PDF)(1.04MB)

About Schering-Plough
Schering Corporation, of Kenilworth, NJ, is a research-based company engaged in the discovery, development, manufacturing, and marketing of pharmaceutical products worldwide. For more information, please visit the company's Web site at www.sch-plough.com.

Contact us at 1-800-222-7579

References:

  • ESPRIT Investigators. Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy. Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial. Lancet. 2000;356:2037–2044.
  • O’Shea JC, Buller CE, Cantor WJ, et al. Long-term efficacy of platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention. JAMA. 2002;287:618–621.

INTEGRILIN is a registered trademark of Millennium Pharmaceuticals, Inc.
Schering Plough
Copyright © 2007, Schering Corporation, Kenilworth, NJ 07033
All rights reserved. ITW0007 01/07