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
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Protection Against Post-Percutaneous Coronary Intervention Microvascular Dysfunction, Ischemia, and Inflammation Among Antiplatelet and Antithrombotic Agents (PROTECT-TIMI-30)1

Objective

To evaluate the efficacy and safety of INTEGRILIN® when administered with indirect thrombin inhibition (unfractionated heparin) or enoxaparin vs direct thrombin inhibition (bivalirudin) alone.

Design

Randomized, open-label, parallel-group, multicenter study of 857 patients with non–ST-elevation ACS undergoing percutaneous coronary intervention (PCI).

INTEGRILIN® & Comparator Doses

Patients were randomly assigned to 1 of 3 treatment regimens:
  • INTEGRILIN® +UFH*
  • INTEGRILIN® + enoxaparin †
  • Bivalirudin ‡

Study medications were administered following diagnostic coronary angiography and before PCI. All patients received aspirin prior to PCI and clopidogrel (75 mg daily) or ticlopidine (250 mg twice daily) if stenting was performed.


Results

Although the primary endpoint of post-PCI CFR was higher in the bivalirudin arm, INTEGRILIN® improved myocardial perfusion and reduced the duration of post-PCI ischemia vs bivalirudin.
  • In angiographically evaluable patients,post-PCI CFR was higher in the bivalirudin arm (1.43 vs 1.33 for pooled INTEGRILIN® arms; P=0.036)
  • Coronary flow improvement (CFI) was significantly greater for INTEGRILIN® (1.55 vs 1.41 for bivalirudin; P=0.036). Absolute improvement in blood flow (corrected TIMI frame count) from pre- to post-PCI was 10 for INTEGRILIN® vs 8 for bivalirudin (P=0.10)
  • INTEGRILIN® significantly increased post-PCI TIMI myocardial perfusion grade (TMPG) vs bivalirudin (57.9 vs 50.9, P=0.048)
  • Death, MI, or ischemia through 48 hours occurred in 18% of patients in the bivalirudin arm compared with 14.2% of patients in the eptifibatide arms (P=0.15), while the composite of death or MI occurred in 8.8% and 6.6%, respectively (P=0.246)
  • INTEGRILIN® significantly reduced duration of ischemia post-PCI vs bivalirudin (36 vs 169 minutes, P=0.01)
  • The rate of TIMI major hemorrhage for the pooled INTEGRILIN® arm was not significantly different from the bivalirudin arm (0.7% vs 0%; P=0.308)
  • The incidence of minor bleeding was 2.5% with INTEGRILIN® vs 0.4% with bivalirudin
* INTEGRILIN® 180-mcg/kg IV bolus, followed 10 minutes later by a second 180-mcg/kg IV bolus and a 2-mcg/kg/min IV infusion for 18 to 24 hours, plus an initial bolus of UFH (50 U/kg), with additional protocol-specified boluses to achieve a target ACT of 200 to 250 seconds.
† Same regimen of INTEGRILIN®, plus 0.5-mg/kg IV infusion of enoxaparin.
‡ 0.75-mg/kg IV bolus and a 1.75-mg/kg/h IV infusion of bivalirudin started simultaneously with the bolus and discontinued after PCI, with additional 0.3-mg/kg IV boluses as needed to maintain an ACT >200 seconds.
 

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

Reference:

  • Gibson CM, Morrow DA, Murphy SA, et al, and the TIMI Study Group. A randomized trial to evaluate the relative protection against post-percutaneous coronary intervention microvascular dysfunction, ischemia, and inflammation among antiplatelet and antithrombotic agents: the PROTECT-TIMI-30 trial. J Am Coll Cardiol. 2006;47:2364–2373.

INTEGRILIN is a registered trademark of Millennium Pharmaceuticals, Inc.
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Copyright © 2007, Schering Corporation, Kenilworth, NJ 07033
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