Eptifibatide

Class: Platelet-Aggregation Inhibitors
Chemical Name: Cyclic(1 - 6) - disulfide - N6amidino - N2 - (3 - mercaptopropionyl) - l - lysylglycyl - l - α - aspartyl - l - tryptophyl - l - prolyl - l - cysteinamide
Molecular Formula: C₃₅H₄₉N₁₁O₉S₂
CAS Number: 148031-34-9
Brands: Integrilin

Introduction

Platelet-aggregation inhibitor;^{1 2 3 10 11 71} a platelet glycoprotein (GP IIb/IIIa)-receptor inhibitor.^{2 6 7 11 14 26 37 44 48 50}

Uses for Eptifibatide

Unstable Angina and Non-ST-Segment Elevation MI

Adjunct to anticoagulant therapy (e.g., unfractionated heparin, low molecular weight heparin), aspirin, and/or clopidogrel to reduce risk of acute cardiac ischemic events (death and/or MI) in patients with non-ST-segment elevation acute coronary syndrome (i.e., unstable angina or non-ST-segment elevation MI) who are managed medically or with PCI.^{1 4 8 40 72 113 116 119 121 123 130 135}

Adjunctive therapy with a GP IIb/IIIa-receptor inhibitor can reduce the incidence of cardiac ischemic events, including subsequent MI and death, in patients with non-ST-segment-elevation acute coronary syndromes.^{16 38 39 40 43 49 52 56}

The American College of Chest Physicians (ACCP) recommends initial (at presentation or diagnosis [“upstream”]) treatment with certain GP IIb/IIIa-receptor inhibitors (i.e., eptifibatide, tirofiban) or clopidogrel in conjunction with an anticoagulant and aspirin in patients with non-ST-segment-elevation acute coronary syndromes who have at least a moderate risk for adverse cardiac ischemic events and who will undergo an early invasive procedure.¹³⁰ Alternatively, ACCP suggests use of eptifibatide or tirofiban in addition to clopidogrel and in conjunction with anticoagulation and aspirin therapy as initial treatment for patients at moderate or greater risk who will undergo an early or delayed invasive procedure.^{123 130}

Eptifibatide and tirofiban not recommended by AHA in women with non-ST-segment-elevation acute coronary syndromes who are at lower risk for adverse cardiac events and are managed with a conservative strategy, because of little demonstrated benefit and possible detrimental effects.¹²⁸

Acute Ischemic Complications of PCI

Adjunct to unfractionated heparin, low molecular weight heparin, aspirin and/or clopidogrel to reduce risk of acute ischemic complications (death, MI, and/or need for urgent revascularization procedures) in patients undergoing PCI, including coronary artery stenting.^{1 4 8 10 11 16 43 116 119 121}

ACCP, ACC, and AHA recommend that therapy with a GP IIb/IIIa-receptor inhibitor be considered in all patients undergoing PCI, particularly in those with refractory non-ST-segment-elevation acute coronary syndromes or other high-risk features.^{113 114 115 116 119 123 128 130} ACC/AHA/SCAI recommend a GPIIb/IIIa-receptor inhibitor without clopidogrel prior to the diagnostic angiogram or just before PCI;^{116 128} however, ACCP recommends a GPIIb/IIIa inhibitor with clopidogrel in such patients. ¹³⁰

Eptifibatide or abciximab recommended for patients with at least moderate risk factors for an ischemic event undergoing PCI, provided a GP IIb/IIIa-receptor inhibitor has not been initiated previously (at presentation or diagnosis [“upstream”]).¹³⁰

Pretreatment with tirofiban or eptifibatide recommended in patients with non-ST-segment-elevation acute coronary syndromes who are at moderate or greater risk for recurrent ischemic events and subsequently undergo PCI.¹³⁰

ACCP recommends bivalirudin with provisional use of a GP IIb/IIIa-receptor inhibitor or unfractionated heparin and a GP IIb/IIIa-receptor inhibitor in patients who are at a low to moderate risk for an ischemic event and who are undergoing PCI.¹³⁰ In patients undergoing elective PCI with stent placement, ACC and AHA consider the use of GP IIb/IIIa-receptor inhibitors (abciximab, eptifibatide, tirofiban) to be reasonable.¹¹⁶

GP IIb/IIIa-receptor inhibitors have also been used in conjunction with heparin and full- or reduced-dose thrombolytic therapy in patients with ST-segment-elevation MI who are to undergo PCI.^{116 122 129 132} ACC/AHA/SCAI suggest eptifibatide or tirofiban as an alternative to abciximab before primary PCI (before coronary angiography) in patients with ST-segment-elevation MI.^{116 122} However, ACCP recommends abciximab in such patients.¹²⁹

Adjunctive Therapy During Thrombolysis to Prevent Reocclusion

Has been used as an adjunct to thrombolytic therapy (e.g., alteplase, tenecteplase) in a limited number of patients to prevent coronary artery reocclusion† following acute MI.^{6 8 13 14 34 43 127}

Eptifibatide Dosage and Administration

General

• 
  

  In patients with unstable angina and non-ST-segment-elevation MI, administer as soon as possible following diagnosis.^{1 8 72}

  
  


• 
  

  Discontinue prior to CABG.¹

  
  

Adjunctive Antithrombotic Therapy: General Considerations

• 
  

  Used in conjunction with aspirin and unfractionated heparin in clinical studies.^{1 4 8 10 12 13 14 19 40}

  
  


• 
  

  Dosage of heparin required to maintain an appropriate activated clotting time (ACT) during concomitant therapy with eptifibatide may be lower than with heparin monotherapy.^{19 72 113 121 129 130 131} (See Specific Drugs under Interactions.)

  
  


• 
  

  Dosage of fondaparinux in conjunction with heparin required to maintain adequate anticoagulation during concomitant therapy with eptifibatide is lower than that required with anticoagulants alone.¹³⁰

  
  


• 
  

  Caution when used in patients requiring thrombolytic therapy.¹ (See Specific Drugs under Interactions.)

  
  

Adjunctive Antithrombotic Therapy When Used in Management of Unstable Angina and Non-ST-Segment Elevation MI

• 
  

  Aspirin: Manufacturer and some clinicians recommend 160–325 mg initially and daily thereafter.^{1 130 133} Other clinicians recommend a maintenance dosage of 75–162 mg daily.^{116 119} ACCP recommends initial and maintenance aspirin dosages of 162–325 and 75–100 mg daily, respectively.^{130 133}

  
  


• 
  

  Clopidogrel in patients managed with conservative medical therapy or early or delayed invasive procedures: 300 mg as a loading dose,¹³⁰ initiate as soon as possible during hospitalization and continue at 75 mg once daily;^{116 119 133} in patients receiving medical management only, continue therapy for ≥1 month but ideally up to 1 year.^{119 135} ACCP recommends a maintenance dosage of 75 mg once daily for 12 months in conjunction with aspirin, and then continuance of aspirin indefinitely in patients receiving medical management only. ¹³³

  
  


• 
  

  Heparin during medical management: In patients weighing ≥70 kg, 5000 units (IV loading dose) followed by continuous IV infusion of 1000 units/hour.¹ In patients weighing <70 kg, 60 units/kg followed by continuous IV infusion of 12 units/kg per hour.¹ Adjust dose to maintain a target aPTT of 50–70 seconds.^{123 130} (See Laboratory Monitoring under Cautions.)

  
  


• 
  

  Heparin in patients undergoing PCI: Administer multiple IV injections of unfractionated heparin based on ACT determinations during PCI to achieve and maintain an ACT of ≥200 seconds.^{1 117 118 121 129 130} ACCP suggests 50–70 units/kg (target ACT of ≥200 seconds).^{8 16 19 45 61 72 89 115 117 118 121 129 130 135}

  
  

Adjunctive Antithrombotic Therapy When Used to Reduce Risk of Acute Ischemic Complications of PCI

• 
  

  Aspirin: Manufacturer recommends 160–325 mg 1–24 hours prior to PCI and daily thereafter.¹ ACC/AHA/SCAI recommend 300–325 mg ≥2 hours, preferably 24 hours, prior to PCI in patients not receiving maintenance therapy with aspirin.^{116 131} In patients who are already receiving maintenance aspirin, give 75–325 mg before the procedure.^{116 131} After PCI, ACCP recommends long-term treatment with aspirin at 75–100 mg daily.¹³³

  
  


• 
  

  Clopidogrel in patients with acute coronary syndromes undergoing PCI: 300–600 mg is generally recommended as a loading dose administered prior to or at the time of the procedure.^{116 121 131}

  
  


• 
  

  Heparin: 50–70 units/kg 6 hours prior to PCI (target ACT of ≥200 seconds).^{1 115 116 121 129 130} Administer additional injections during PCI to maintain an ACT of 200–300 seconds.^{1 116 131} (See Laboratory Monitoring under Cautions.) In patients who received heparin in conjunction with thrombolytic agents prior to PCI, ACC and AHA and other clinicians recommend administering additional heparin injections during PCI.^{131 132} Consider a lower dosage of heparin in women and geriatric patients receiving a GP IIb/IIIa-receptor inhibitor to decrease the increased risk of minor bleeding.^{116 128} Postprocedural use of heparin not recommended.^{1 10 26 45 115 116 121}

  
  


• 
  

  Fondaparinux: In patients managed initially with fondaparinux at presentation or diagnosis (“upstream”), a GP IIb/IIIa-receptor inhibitor, and a delayed invasive strategy, ACCP recommends additional IV injections of fondaparinux sodium† (2.5 mg) and heparin sodium (e.g., 50–60 units/kg) be given at the time of the procedure.^{130 131}

  
  

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV injection followed by IV infusion using a controlled-infusion device (e.g., pump).¹

For IV injection, withdraw appropriate dose from the 10-mL vial and administer undiluted.^{1 71}

For continuous IV infusion, spike the 100-mL vial with a vented infusion set; center spike within the circle on stopper top.¹ Administer solution directly from vial.^{1 8 71}

Discard unused portion.¹

Dilution

Administer undiluted.¹

Rate of Administration

For IV injection, administer over 1–2 minutes.^{1 71}

Dosage

Adults

Unstable Angina and Non-ST-Segment Elevation MI

IV

180 mcg/kg by IV injection as soon as possible following diagnosis, followed by IV infusion of 2 mcg/kg per minute until hospital discharge or initiation of CABG, or for ≤72 hours.^{1 8 72}

If patient undergoes PCI while receiving eptifibatide, continue infusion (at 2 mcg/kg per minute) until hospital discharge or for ≤18–24 hours after procedure, whichever comes first, up to a maximum of 96 hours.¹

Acute Ischemic Complications of PCI

IV

180 mcg/kg by IV injection immediately before initiation of PCI, immediately followed by IV infusion of 2 mcg/kg per minute and a second IV injection of 180 mcg/kg 10 minutes after the first IV injection.^{1 117 118 129 130} Optimal time to initiate treatment with eptifibatide prior to PCI has not been established.¹³¹

Continue infusion (at 2 mcg/kg per minute) until hospital discharge or for ≤18–24 hours, whichever comes first.^{1 130} A minimum infusion period of 12 hours is recommended.^{1 129}

Prescribing Limits

Adults

Unstable Angina and Non-ST-Segment Elevation MI

IV

Maximum IV infusion of 72 hours.^{1 8 72}

In patients undergoing PCI, maximum IV infusion of 96 hours.¹

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.⁸

Renal Impairment

Unstable Angina and Non-ST-Segment Elevation MI

No dosage adjustment required in patients with mild to moderate renal impairment (Cl_cr ≥50 mL/minute).¹

In patients with Cl_cr <50 mL/minute, 180 mcg/kg by IV injection as soon as possible following diagnosis, followed by IV infusion of 1 mcg/kg per minute.¹

Acute Ischemic Complications of PCI

In patients with Cl_cr <50 mL/minute, 180 mcg/kg by IV injection immediately before initiation of PCI, followed by IV infusion of 1 mcg/kg per minute and a second IV injection of 180 mcg/kg 10 minutes after the first IV injection.¹

Geriatric Patients

No dosage adjustment was made for geriatric patients in clinical trials.¹ (See Geriatric Use under Cautions.)

Cautions for Eptifibatide

Contraindications

• 
  

  History of bleeding diathesis^{1 10 13} or active abnormal bleeding within previous 30 days.^{1 10 12 13}

  
  


• 
  

  Severe uncontrolled hypertension (systolic BP >200 mm Hg or diastolic BP >110 mm Hg with antihypertensive therapy).^{1 10 13}

  
  


• 
  

  Recent (within 6 weeks) major surgery.^{1 10 12 13}

  
  


• 
  

  History of stroke within 30 days or any history of hemorrhagic stroke.^{1 10 12 13}

  
  


• 
  

  Current or planned therapy with another GP IIb/IIIa-receptor inhibitor.¹

  
  


• 
  

  Patients undergoing renal dialysis.¹

  
  


• 
  

  Known hypersensitivity to eptifibatide or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Bleeding

Risk of major bleeding (e.g., intracranial hemorrhage, GU or GI bleeding, bleeding at femoral vascular access site)^{1 8 17 71 85 117} and minor bleeding (e.g., spontaneous gross hematuria, spontaneous hematemesis);^{1 8 17 72 85} may require blood or platelet transfusions.^{1 10 117} (See Bleeding Precautions and see Laboratory Monitoring under Cautions.) Patients weighing <70 kg at increased risk of major bleeding.¹

If bleeding cannot be controlled by pressure, discontinue eptifibatide and concomitant heparin immediately.¹

Use not recommended in patients with hematocrit <30%.^{8 72}

Thrombocytopenia

Thrombocytopenia reported.^{110 111} Severe thrombocytopenia (platelet count <20,000/mm³) reported less frequently than with abciximab.^{8 26 40 55 72 93 99 111}

Determine platelet counts prior to treatment and periodically (e.g., daily)⁷² during concomitant eptifibatide and heparin therapy.^{8 72 88} Consider possibility of heparin-induced thrombocytopenia in patients receiving concomitant heparin therapy.^{29 55 93 107 111}

If platelet count decreases to <100,000/mm³, discontinue eptifibatide and heparin and initiate appropriate treatment and monitoring.¹ Consider platelet transfusions for management of severe thrombocytopenia.^{55 93 106 111 112}

No clinical experience with eptifibatide in patients with platelet counts <100,000/mm³.¹

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis reported.¹

Major Toxicities

General Precautions

Bleeding Precautions

To reduce risk of bleeding, adhere to strict anticoagulation guidelines; use a short course of low-dose, weight-adjusted heparin; avoid vascular and other trauma; carefully manage vascular (e.g., femoral artery) access site; and monitor all potential bleeding sites during and following treatment.^{1 26 29 43 45 52 97 107 109} Manufacturer recommends that concomitant thrombolytic therapy be used with caution.¹

In patients undergoing PCI, use caution in the placement, maintenance, and removal of vascular access sheath.^{1 26 44 45 52} When inserting sheath, puncture only anterior wall of femoral artery; avoid Seldinger (through and through) technique.^{8 26 72} Observe appropriate precautions while sheath is in place (e.g., complete bed rest, elevation of head ≤30°, restrain limb in which sheath is inserted, frequent monitoring of vascular access site and distal pulse in the involved limb).^{26 27 72} Following PCI, consider early sheath removal (during eptifibatide IV infusion).¹ Prior to removal of sheath, discontinue heparin for 3–4 hours and allow aPTT to return to <45 seconds or ACT to <150–180 seconds.^{1 26 27 35 44 45 115} Discontinue eptifibatide and heparin and achieve hemostasis (by applying pressure to femoral artery for at least 20–30 minutes after sheath removal^{26 27} ) at least 2–4 hours before hospital discharge.¹ Measure and monitor hematomas for enlargement.^{8 26 72}

To avoid vascular and other trauma, minimize needle punctures (e.g., arterial, IM, IV, lumbar, sub-Q, intradermal), cutdown sites, and use of nasotracheal intubation, nasogastric tubes, urinary catheters, and automatic BP cuffs²⁶ during and following treatment;^{1 8 72} avoid establishment of IV access at noncompressible sites (e.g., subclavian or jugular veins);¹ consider using an indwelling venipuncture device (e.g., heparin lock) for drawing blood; document and monitor vascular puncture sites; and remove dressings gently and carefully.^{8 26 72}

Laboratory Monitoring

Prior to administration, obtain hematocrit or hemoglobin, platelet count, S_cr, and PT or aPTT.¹ In patients undergoing PCI, also obtain ACT prior to administration.¹

In patients with unstable angina or non-ST-segment-elevation MI undergoing medical management, target aPTT between 50–70 seconds.¹

In patients undergoing PCI, ACC, AHA, and manufacturer recommend targeting ACT between 200–300 seconds during PCI;^{1 116} ACCP suggests a target ACT of ≥200 seconds to reduce risk of major bleeding.¹²¹

Monitor aPTT or ACT prior to arterial sheath removal; do not remove sheath unless aPTT ≤45 seconds or ACT <150–180 seconds.^{1 26 27 35 44 45 115}

Specific Populations

Pregnancy

Category B.¹

Lactation

Not known whether eptifibatide is distributed into milk.¹ Use with caution.¹

Pediatric Use

Safety and efficacy not established.^{1 8}

Geriatric Use

No substantial differences in efficacy relative to younger adults.¹ However, increased incidence of bleeding complications.¹

Hepatic Impairment

Use contraindicated in patients with hepatic disease severe enough to alter synthesis of coagulation factors.⁸

Renal Impairment

Decreased clearance and increased plasma concentrations in patients with moderate to severe renal impairment (estimated Cl_cr <50 mL/minute);¹ reduced dosage recommended in such patients.¹ (See Renal Impairment under Dosage and Administration.) Use contraindicated in patients undergoing renal dialysis.¹

Common Adverse Effects

Bleeding,¹ hypotension.^{1 8 43}

Interactions for Eptifibatide

Specific Drugs

Drug	Interaction	Comments
Anticoagulants, oral	Potential increased risk of bleeding1	Use with caution1
Dipyridamole	Potential increased risk of bleeding1	Use with caution1
Enoxaparin	Pharmacokinetic or pharmacodynamic (e.g., effect on platelet aggregation) interaction unlikely1
GP IIb/IIIa-receptor inhibitors (abciximab, tirofiban)	Possible additive pharmacologic effects1 4	Avoid concomitant use1 4
Heparin	Possible additive effects on ACT19 116 121	Reduce dosage of heparin to maintain appropriate ACT19 116 121
NSAIAs	Potential increased risk of bleeding1	Use with caution1
Thrombolytics (e.g., alteplase, streptokinase)	Increased risk of bleeding, including that requiring blood transfusions1 5 34	Use with caution1 4 34 43 72

Eptifibatide Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations achieved within 5 minutes and steady-state concentrations attained within 4–6 hours following IV administration.^{1 4 9 41 43}

Onset

Maximal inhibition of platelet aggregation occurs within 15 minutes following IV administration and is rapidly reversible.^{1 8 12}

Duration

Platelet aggregation usually returns to normal within 4–8 hours after discontinuing therapy.^{8 13 31 41 43}

Special Populations

Steady-state plasma concentrations double in patients with moderate to severe renal impairment (estimated Cl_cr <50 mL/minute).¹

Increased plasma concentrations in geriatric patients.¹

Distribution

Extent

Not known whether eptifibatide is distributed into breast milk.¹

Plasma Protein Binding

Approximately 25% (mainly albumin).^{1 8 41 43}

Elimination

Metabolism

Principally metabolized to a less active metabolite;^{1 9 41 71} 27% of dose is converted in plasma into naturally occurring amino acids.^{4 41}

Elimination Route

Eliminated by renal (40–50% of total body clearance)^{1 8 9 71} and nonrenal mechanisms,^{9 41 43 71} mainly as parent drug and metabolites.¹ In healthy men, approximately 98, 1.5, and 0.8% of a single dose was recovered in urine, feces, and breath carbon dioxide, respectively.⁹

May be removed by hemodialysis.¹

Half-life

2.5–2.8 hours in patients with CAD;^{1 8 19 38} 0.83–2.4 hours in healthy individuals.^{2 8 42 71}

Special Populations

Clearance reduced by 50% in patients with moderate to severe renal impairment (estimated Cl_cr <50 mL/minute).¹

Reduced total body clearance in geriatric patients.¹

Stability

Storage

Parenteral

Injection

2–8°C.^{1 8} Protect from light.^{1 8}

May store at room temperature (15–30°C) for ≤2 months.^{1 8}

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

No incompatibilities observed with IV administration sets; no compatibility studies performed with polyvinyl chloride (PVC) bags.¹

Solution Compatibility¹

*Infusion may contain up to 60 mEq/L of potassium chloride.¹

Compatible
Dextrose 5% and sodium chloride 0.9%*
Sodium chloride 0.9%*

Drug Compatibility¹

Admixture CompatibilityHID

Compatible
Alteplase
Amiodarone HCl
Atropine
Bivalirudin
Dobutamine HCI
Heparin sodium
Lidocaine HCI
Meperidine HCI
Metoprolol tartrate
Midazolam HCI
Morphine sulfate
Nitroglycerin
Verapamil HCI
Incompatible
Furosemide

ActionsActions

• 
  

  Binds selectively to platelet GP IIb/IIIa receptors and reversibly inhibits platelet aggregation (by preventing binding of fibrinogen, von Willebrand factor, and other adhesive ligands to GP IIb/IIIa receptors).^{1 2 3 4 7 8 16 37 71}

  
  


• 
  

  Modest effect on hemostatic indices (e.g., bleeding times) and platelet function; normal hemostasis restored more rapidly than with abciximab.^{1 2 6 10 17 72}

  
  


• 
  

  Usually does not affect PT or aPTT when administered as monotherapy.¹

  
  

Advice to Patients

• 
  

  Risk of serious bleeding or hemorrhage.¹

  
  


• 
  

  Importance of close laboratory monitoring.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Eptifibatide

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IV Use	2 mg/mL (20 mg)	Integrilin	Schering
		0.75 mg/mL (75 mg)	Integrilin	Schering

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions September 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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3. Phillips DR, Teng W, Arfsten A et al. Effect of Ca²⁺ on GP IIb-IIIa interactions with Integrilin: enhanced GP IIb-IIIa binding and inhibition of platelet aggregation by reductions in the concentration of ionized calcium in plasma anticoagulated with citrate. Circulation. 1997; 96:1488-94. [PubMed 9315536]

4. Key Pharmaceuticals. Integrilin™ (eptifibatide) product monograph. Kenilworth, NJ; 1998 Aug.

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6. White H. Unmet therapeutic needs in the management of acute ischemia. Am J Cardiol. 1997; 80(Suppl 4A):2b-10b. [IDIS 392824] [PubMed 9291240]

7. Le Breton H, Plow EF, Topol EJ et al. Role of platelets in restenosis after percutaneous coronary revascularization. J Am Coll Cardiol. 1996; 28:1643-51. [PubMed 8962547]

8. Cor Therapeutics, South San Francisco, CA, and Key Pharmaceuticals, Kenilworth, NJ: Personal communication.

9. Alton KB, Kosoglou T, Baker S et al. Disposition of¹⁴C-eptifibatide after intravenous administration to healthy men. Clin Ther. 1998; 20: 307-323. [IDIS 405663] [PubMed 9589822]

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13. Ohman EM, Kleiman NS, Gacioch G et al. Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockage with Integrilin in acute myocardial infarction: results of a randomized, placebo-controlled, dose-ranging trial. Circulation. 1997; 98:846-54.

14. Moliterno DJ, Topol EJ. Conjunctive use of platelet glycoprotein IIb/IIIa antagonists and thrombolytic therapy for acute myocardial infarction. Thromb Haemost. 1997; 78:214-9. [IDIS 392081] [PubMed 9198156]

15. Harrington RA, Ohman EM, Sigmon KN et al. Intensity of inhibition of the platelet glycoprotein IIb/IIIa receptor differs among disease states. Circulation. 1995; 92(Suppl 1):488-9.

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19. Tcheng JE, Harrington RA, Kottke-Marchant K et al. Multicenter, randomized, double-blind, placebo-controlled trial of the platelet integrin glycoprotein IIb/IIIa blocker Integrilin in elective coronary intervention. Circulation. 1995; 91:2151-7. [IDIS 347920] [PubMed 7697843]

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22. Ohlstein EH, Storer B, Fujita T et al. Tissue-type plasminogen activator and streptokinase induce platelet hyperaggregability in the rabbit. Thromb Res. 1987; 46:575-85. [PubMed 3112993]

23. Fitzgerald DJ, Catella F, Roy L et al. Marked platelet activation in vivo after IV streptokinase in patients with acute myocardial infarction. Circulation. 1988; 77:142-50. [IDIS 312893] [PubMed 3275505]

24. Gold HK, Coller BS, Yashuda T et al. Rapid and sustained coronary artery recanalization with combined bolus injection of recombinant tissue-type plasminogen activator and monoclonal antiplatelet GPIIbIIIa antibody in a canine preparation. Circulation. 1988; 77:670-7. [PubMed 3124974]

25. Gold HK, Leinbach RC. Prevention of acute reocclusion after thrombolysis with IV recombinant tissue plasminogen activator. In: Sobel BE, Collen D, Grossbard EB, eds. Tissue plasminogen activator in thrombolytic therapy. New York: Marcel Dekker, Inc; 1987:115-30.

26. Eli Lilly and Company. ReoPro (abciximab) injection for intravenous administration prescribing information. Indianapolis, IN: 1998 Feb 12.

27. Bittl JA, Levin DC. Coronary arteriography. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. 5th ed. Philadelphia: WB Saunders Company; 1997:240-72.

28. Sanofi. Plavix (clopidogrel bisulfate) tablets prescribing information. New York, NY: 1997 Nov.

29. Merck & Co. Aggrastat (tirofiban hydrochloride) injection prescribing information. West Point, PA; 1998 May.

30. Agency for Health Care Policy and Research. Diagnosing and managing unstable angina. 1994. (AHCPR publication no. 94-0603)

31. Jennings L, Tardiff B, Scarborough R et al. Comparison of receptor occupancy and platelet aggregation response of eptifibatide administered intravenously in patients with unstable angina or non-Q-wave myocardial infarction. J Am Coll Cardiol. 1998; 31(Suppl A): 93A.

32. McClure M, Kleiman NS, Berdan LG et al. Thrombocytopenia in a large