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Class: Platelet-aggregation Inhibitors
- Antithrombotic Agents
- Platelet-aggregation Inhibitors
- GP IIb/IIIa Receptor 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

Medically reviewed by Last updated on Sep 9, 2019.


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

Non-ST-Segment-Elevation Acute Coronary Syndromes

Adjunct to anticoagulant therapy (e.g., heparin [referring throughout this monograph to unfractionated heparin], low molecular weight heparin [LMWH]), aspirin, and a P2Y12 platelet adenosine diphosphate (ADP)-receptor antagonist (e.g., clopidogrel, prasugrel, ticagrelor) to reduce risk of acute cardiac ischemic events (death and/or MI) in patients with non-ST-segment-elevation acute coronary syndromes (NSTE ACS) (i.e., unstable angina or non-ST-segment-elevation MI [NSTEMI]) who are managed medically or with PCI.1 4 8 40 72 113 994 995 1100

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 NSTE ACS.16 40 43 49 52 56

The American College of Cardiology Foundation (ACCF) and AHA recommend either clopidogrel or IV administration of a GP IIb/IIIa-receptor inhibitor in addition to aspirin therapy prior to diagnostic angiography (“upstream”) in patients in whom an initial invasive management strategy is planned; eptifibatide or tirofiban is the preferred GP IIb/IIIa inhibitor for this use.991 Abciximab is recommended only if there is no appreciable delay before angiography and PCI is likely to be performed.991

The American College of Chest Physicians (ACCP) states that a clear risk-benefit profile has not been established for use of GP IIb/IIIa-receptor inhibitors in patients with ACS who are not routinely scheduled for early revascularization.1016

Eptifibatide and tirofiban not recommended by AHA in women with NSTE ACS 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 anticoagulant therapy (heparin, LMWH), aspirin, and a P2Y12-receptor antagonist (e.g., clopidogrel, prasugrel, ticagrelor) 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 43 994 995

ACCF, AHA, the Society for Cardiovascular Angiography and Interventions (SCAI), and other experts currently do not recommend routine use of GP IIb/IIIa-receptor inhibitors in patients with ST-segment-elevation MI (STEMI) undergoing PCI; however, selective use of these drugs as an adjunct to heparin may be reasonable in certain high-risk patients (e.g., those with large anterior MI and/or large thrombus).994 1016

ACCF/AHA/SCAI state that administration of a GP IIb/IIIa-receptor inhibitor at the time of PCI as an adjunct to heparin may be particularly useful in patients with NSTE ACS who have high-risk features (e.g., elevated troponin) and are not receiving bivalirudin and are not adequately pretreated with clopidogrel.994

Regarding choice of GP IIb/IIIa-receptor inhibitor in patients undergoing PCI, IV abciximab, “double-bolus” IV eptifibatide, and high-dose tirofiban by direct IV injection all produce a high degree of platelet inhibition and reduce ischemic complications.994

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

Eptifibatide Dosage and Administration


  • In patients with NSTE ACS, 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 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 72 113 994 (See Specific Drugs under Interactions.)

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

Adjunctive Antithrombotic Therapy When Used in Management of NSTE ACS

  • Aspirin: Manufacturer recommends 160–325 mg initially and daily thereafter.1

  • Heparin sodium 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.1 (See Laboratory Monitoring under Cautions.)

  • Heparin sodium in patients undergoing PCI: Administer multiple IV injections of heparin based on ACT determinations during PCI to achieve and maintain an ACT of ≥200 seconds.1 117 118

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 ACCF/AHA/SCAI recommends that aspirin 325 mg be given prior to PCI in patients not already receiving maintenance aspirin therapy.994 Patients already receiving maintenance aspirin therapy should receive a dose of 81–325 mg before the procedure.994

  • P2Y12-receptor antagonist: A loading dose of clopidogrel, prasugrel, or ticagrelor also is recommended prior to PCI in patients undergoing stent placement.994 995

  • Heparin: 50–70 units/kg 6 hours prior to PCI (target ACT of ≥200 seconds).1 Administer additional injections during PCI to maintain an ACT of 200–300 seconds.1 (See Laboratory Monitoring under Cautions.) 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.128 Postprocedural use of heparin not recommended.1 10 26


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


Administer undiluted.1

Rate of Administration

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




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

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

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

Prescribing Limits



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


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

In patients with Clcr <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 Clcr <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


  • History of bleeding diathesis1 10 13 or active abnormal bleeding within previous 30 days.1 10 12 13

  • Severe uncontrolled hypertension (SBP >200 mm Hg or DBP >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




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 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 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 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 Discontinue eptifibatide and heparin and achieve hemostasis (by applying pressure to femoral artery for at least 20–30 minutes after sheath removal26 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, Scr, 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 the manufacturer recommends targeting ACT between 200–300 seconds during PCI.1

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

Specific Populations


Category B.1


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 Clcr <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




Anticoagulants, oral

Potential increased risk of bleeding1

Use with caution1


Potential increased risk of bleeding1

Use with caution1


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


Possible additive effects on ACT19

Reduce dosage of heparin to maintain appropriate ACT19


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



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


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


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 Clcr <50 mL/minute).1

Increased plasma concentrations in geriatric patients.1



Not known whether eptifibatide is distributed into breast milk.1

Plasma Protein Binding

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



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


2.5–2.8 hours in patients with CAD;1 8 19 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 Clcr <50 mL/minute).1

Reduced total body clearance in geriatric patients.1





2–8°C.1 8 Protect from light.1 8

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


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


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


Dextrose 5% and sodium chloride 0.9%*

Sodium chloride 0.9%*

Drug Compatibility1
Admixture CompatibilityHID



Amiodarone HCl



Dobutamine HCI

Heparin sodium

Lidocaine HCI

Meperidine HCI

Metoprolol tartrate

Midazolam HCI

Morphine sulfate


Verapamil HCI




  • 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.)


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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.



Dosage Forms


Brand Names



Injection, for IV Use

2 mg/mL (20 mg)



0.75 mg/mL (75 mg)



AHFS DI Essentials™. © Copyright 2020, Selected Revisions September 18, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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


1. Schering. Integrilin (eptifibatide) injection prescribing information. Kenilworth, NJ; 2007 Mar.

2. Phillips DR, Scarborough RM. Clinical pharmacology of eptifibatide. Am J Cardiol. 1997; 80(Suppl 4A):11b-20b.

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.

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

5. Braunwald E, Maseri A, Armstrong PW et al. Rationale and clinical evidence for the use of GP IIb/IIIa inhibitors in acute coronary syndromes. Eur Heart J. 1998; 19(Suppl D):D22-30.

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

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.

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.

10. Anon. Randomised placebo-controlled trial of effect of eptifibatide on complication of percutaneous coronary intervention: IMPACT-II. Integrilin to Minimise Platelet Aggregation and Coronary Thrombosis-II. Lancet. 1997; 349:1422-8.

11. Tcheng JE. Impact of eptifibatide on early ischemic events in acute ischemic coronary syndromes: a review of the IMPACT II trial. Am J Cardiol. 1997; 80(Suppl 4A):21B-8B.

12. Harrington RA, Kleiman NS, Kottke-Marchant K et al. Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention. Am J Cardiol. 1995; 76:1222-7.

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.

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.

16. Tcheng JE. Glycoprotein IIb/IIIa receptor inhibitors: putting the EPIC, IMPACT II, RESTORE, and EPILOG trials into perspective. Am J Cardiol. 1996; 78(Suppl 3A):35-40.

17. Kleiman NS. Primary and secondary safety endpoints from IMPACT II. Am J Cardiol. 1997; 80(Suppl 4A):29B-33B.

18. Plow EF, Ginsberg MH. Molecular basis of platelet function. In: Hoffman R, Benz EJ, Shattil SJ et al, eds. Hematology. 2nd ed. Churchill Livingstone. New York, NY. 1995:1524-35.

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.

20. Catella-Lawson F, Fitzgerald GA. Confusion in reperfusion: problems in the clinical development of antithrombotic drugs. Circulation. 1997; 95: 793-5.

21. Loscalzo J, Braunwald E. Tissue plasminogen activator. N Engl J Med. 1988; 319:925-31.

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.

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.

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.

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, international trial of the GP IIb/IIIa inhibitor eptifibatide in patients with acute coronary syndromes. J Am Coll Cardiol. 1998; 31(Suppl A):93A.

33. Lincoff AM, Harrington RA, Califf RM et al. Clinical efficacy of Integrilin in unstable angina is accompanied by a modest increase in hemorrhagic risk: the PURSUIT trial. J Am Coll Cardiol. 1998; 31(Suppl A):185A.

34. Ronner E, van Kesteren HAM, Zijnen P et al. Combined therapy with streptokinase and Integrilin. J Am Coll Cardiol. 1998; 31(Suppl A):191A.

35. Simko RJ, Tsung FFW, Stamek EJ et al. Activated clotting time versus activated partial thromboplastin time for therapeutic monitoring of heparin. Ann Pharmacother. 1995; 29:1015-21.

37. Harrington RA. Design and methodology of the PURSUIT trial: evaluating eptifibatide for acute coronary syndromes. Am J Cardiol. 1997; 80(Suppl 4A):34b-8b.

40. PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med. 1998; 339:436-43.

41. Cor Therapeutics. Integrilin™ (eptifibatide). Summary basis of approval: clinical pharmacology/biopharmaceutics review. Reference No.: 20-718. Kenilworth, NJ. 1998.

42. Charo IF, Scarborough RM, du Mee CP et al. Pharmacodynamics of the GPIIb-IIIa antagonist integrilin: phase I clinical studies in normal healthy volunteers. Circulation. 1992; 86(Suppl I):I-260.

43. Goa KL, Noble S. Eptifibatide. A review of its use in patients with acute coronary syndromes and/or undergoing percutaneous coronary intervention. Drugs. 1999; 57:439-62.

44. The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med. 1994; 330:956-61.

46. Levin T. Eptifibatide in acute coronary syndromes. N Engl J Med. 1999; 340:60.

47. Harrington RA, Simoons ML, Topol EJ. Eptifibatide in acute coronary syndromes. N Engl J Med. 1999; 340:61.

48. Davies MJ. The role of plaque pathology in coronary thrombosis. Clin Cardiol. 1997; 20(Suppl I):I-2-7.

49. Topol EJ. Targeted approaches to thrombus formation: an end to the shotgun approach. Clin Cardiol. 1997; 20(Suppl I):I-22-6.

50. de Feyter PJ. The benefits and risks of coronary intervention—-balancing the equation. Clin Cardiol. 1997; 20(Suppl I):I-14-21.

51. Merlini PA, Bauer KA, Oltrona L et al. Thrombin generation and activity during thrombolysis and concomitant heparin therapy in patients with acute myocardial infarction. J Am Coll Cardiol. 1995; 25:203-9.

52. Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med. 1995; 332:1553-9.

53. Moll S. Eptifibatide in acute coronary syndromes. N Engl J Med. 1999; 340:60-1.

54. Alexander JH, Harrington RA, Tuttle RH et al. Prior aspirin use predicts worse outcomes in patients with non-ST elevation acute coronary syndromes. Am J Cardiol. 1999; 83:1147-51.

55. Lincoff AM. Trials of platelet glycoprotein IIb/IIIa receptor antagonists during percutaneous coronary revascularization. Am J Cardiol. 1998; 82:36P-42P.

56. Alexander JH, Harrington RA. Recent antiplatelet drug trials in the acute coronary syndromes. Clinical interpretation of PRISM, PRISM-PLUS, PARAGON A, and PURSUIT. Drugs. 1998; 56:965-76.

57. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy—I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ. 1994; 308:81-106.

58. Théroux P. Antiplatelet therapy: do the new platelet inhibitors add significantly to the clinical benefits of aspirin? Am Heart J. 1997; 134:S62-70.

59. Théroux P, Ouimet H, McCans J et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med. 1988; 319:1105-11.

60. Catella-Lawson F, FitzGerald GA. Trials in myocardial infarction. Circulation. 1997; 96:3815.

61. Kleiman NS. A risk-benefit assessment of abciximab in angioplasty. Drug Saf. 1999; 20:43-57.

62. Detre KM, Holmes DR Jr, Holubkov R et al. Incidence and consequences of periprocedural occlusion: the 1985–1986 National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry. Circulation. 1990; 82:739-50.

63. Cairns JA, Gent M, Singer J et al. Aspirin, sulfinpyrazone, or both in unstable angina: results of a Canadian multicenter trial. N Engl J Med. 1985; 313:1369-75.

64. Lewis HD, Davies JW, Archibald DG et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1983; 309:396-403.

65. The RISC Group. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet. 1990; 336:827-30.

66. Cohen M, Adams PC, Gareth P et al. Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users: Primary end points analysis for the ATACS trial. Circulation. 1994; 89:81-8.

67. Oler A, Whooley MA, Oler J et al. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina: a meta-analysis. JAMA. 1996; 276:811-5.

68. Théroux P, Waters D, Qiu S et al. Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina. Circulation. 1993; 88(5 Pt 1):2045-8.

69. Cairns J, Théroux P, Armstrong P et al. Unstable angina—Report from a Canadian expert round table. Can J Cardiol. 1996; 12:1279-92.

70. Sambol NC, Tcheng JE, Kitt M et al. Population pharmacokinetics (PK) and pharmacodynamics (PD) of integrelin, a platelet aggregation inhibitor. Clin Pharmacol Ther. 1996; 59:150.

71. Anon. Eptifibatide. Drugs Future. 1998; 23:585-90.

72. Reviewers’ comments (personal observations).

73. Freedman SB, Dunn RF, Bernstein L et al. Influence of coronary collateral blood flow on the development of exertional ismchemia and Q wave infarction in patients with severe single-vessel disease. Circulation. 1985; 71:681-6.

74. Théroux P, Fuster V. Acute coronary syndromes: unstable angina and non-Q-wave myocardial infarction. Circulation. 1998; 97:1195-1206.

75. Tonkin AM, Aroney CN. Guidelines for managing patients with unstable angina: rating the evidence and rationale for treatment. Med J Aust. 1997; 16:644-7.

76. Cohen M, Demers C, Gurfinkel EP et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med. 1997; 337: 447-52.

77. Armstrong PW. Heparin in acute coronary disease-requiem for a heavyweight? N Engl J Med. 1997; 337:492-4. (IDIS 389821)

78. Swahn E, Wallentin L for the FRISC study group. Low-molecular weight heparin (fragmin) during instability in coronary artery disease (FRISC). Am J Cardiol. 1997; 80(Suppl. 5A):25E-9E.

79. Berdan L, Weatherly BD, Widimsky P et al. Global gender variations in the care of patients with acute coronary syndromes. Circulation. 1998; 98(Suppl. 1):I-560.

80. Holmes DR, White HD, Hasdai D et al. Relationship between age and outcome in patients with acute ischemic syndromes randomized to eptifibatide or placebo: a report from the PURSUIT trial. Circulation. 1998; 98(Suppl. 1):I-359.

81. Greenbaum AB, Hudson MP, MacAulay CM et al. Timing of events after hospitalization for acute coronary syndromes. Circulation. 1998; 98(Suppl. 1):I-630.

82. Berdan LG, Kleiman NS, Guerci A et al. Unstable angina in the US: patients and management. Circulation. 1998; 98(Suppl. 1):I-359.

83. Gilchrist IC, Thel MC, Joseph D et al. Enhanced platelet Iib/IIIa inhibition with eptifibatide via high-dose, double-bolus dosing: final results of the PRIDE study. Circulation. 1998; 98(Suppl.1):I-844-5.

84. Akkerhuis M, Boersma E, Harrington RA et al. Eptifibatide protects against adverse cardiac complications both before and during percutaneous intervention in patients with acute coronary syndromes without Stelevation. J Am Coll Cardiol. 1999; 33(Suppl. A):40A.

85. Rao AK, Pratt C, Berke A et al. Thrombolysis in myocardial infarction (TIMI) trial-phase I: hemorrhagic manifestations and changes in plasma fibrinogen and fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol. 1988; 11:1-11.

86. Vorchheimer DA, Guzman IC, Greenberg S et al. Safety and efficacy of eptifibatide therapy in patients with previous stroke or transient ischemic attack. J Am Coll Cardiol. 1999; 33(Suppl. A):330A.

87. Mahaffey KW, Harrington RA, Simoons ML et al. Stroke in patients with acute coronary syndromes: incidence and outcomes in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial. Circulation. 1999; 99:2371-7.

88. Wyeth-Ayerst Laboratories. Heparin sodium injection prescribing information. In: Physicians’ desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:3305-7.

89. The EPILOG Investigators. Platelet glycoprotein Iib/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med. 1997; 336:1689-96.

90. Fragmin during Instability in Coronary Artery Disease (FRISC) study group. Low-molecular-weight heparin during instability in coronary artery disease. Lancet. 1996; 347:561-8.

91. Scarborough RM, Kleiman NS, Phillips DR. Platelet glycoprotein IIb/IIIa antagonists: what are the relevant issues concerning their pharmacology and clinical use? Circulation. 1999; 100:437-44.

92. Kleiman NS, Lincoff AM, Ohman EM et al. Glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: pathophysiologic foundation and clinical findings. Am Heart J. 1998; 136:532-42.

93. Madan M, Berkowitz SD, Tcheng JE. Glycoprotein IIb/IIIa integrin blockade. Circulation. 1998; 98:2629-35.

94. Zaacks SM, Liebson PR, Calvin JE et al. Unstable angina and non-Q wave myocardial infarction: does the clinical diagnosis have therapeutic implications? J Am Coll Cardiol. 1999; 33:107-18.

95. Chesebro JH, Badimon JJ. Platelet glycoprotein IIb/IIIa receptor blockade in unstable coronary disease. N Engl J Med. 1998; 338:1539-41.

96. Kong DF, Califf Rm, Miller DP et al. Clinical outcomes of therapeutic agents that block the platelet glycoprotein IIb/IIIa integrin in ishemic heart disease. Circulation. 1998; 98:2829-35.

97. Reviewers’ comments (personal observations) on tirofiban.

98. The Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. N Engl J Med. 1998; 338:1488-97.

99. Vorchheimer DA, Badimon JJ, Fuster V. Platelet glycoprotein IIb/IIIa receptor antagonists in cardiovascular disease. JAMA. 1999; 281:1407-14.

100. The RESTORE Investigators. Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. Circulation. 1997; 96:1445-53.

101. Gibson CM, Goel M, Cohen DJ et al. Six-month angiographic and clinical follow-up of patients prospectively randomized to receive either tirofiban or placebo during angioplasty in the RESTORE trial. J Am Coll Cardiol. 1998; 32:28-34.

102. Dobesh PP, Latham KA. Advancing the battle against ischemic syndromes: a focus on the GP-IIb/IIIa inhibitors. Pharmacotherapy. 1998; 18:663-85.

104. Antman EM, Fox KM for the International Cardiology Forum. Guidelines for the diagnosis and management of unstable angina and non-Q-wave myocardial infarction: proposed revisions. Am Heart J. 2000; 139:461-75.

105. Kaul S, Shah PK. Low molecular weight heparin in acute coronary syndrome: evidence for superior or equivalent efficacy compared with unfractionated heparin? J Am Coll Cardiol. 2000; 35:1699-702.

106. Quinn M, Fitzgerald DJ. Long-term administration of glycoprotein IIb/IIIa antagonists. Am Heart J. 1998; 135:S113-8.

107. Merck & Co. Product information form for American hospital formulary service: Aggrastat (tirofiban hydrochloride). West Point, PA; 1998.

108. Armstrong PW. Pursuing progress in acute coronary syndromes. Circulation. 1999; 100:1586-9.

109. Merck & Co., West Point, PA: Personal communication on tirofiban.

110. Giugliano RP, Hyatt RR. Thrombocytopenia with GP IIb/IIIa inhibitors: a meta-analysis. J Am Coll Cardiol. 1998; 31(Suppl 2A):185A.

111. Ferguson JJ, Kereiakes DJ, Adgey AAJ et al. Safe use of platelet GP IIb/IIIa inhibitors. Am Heart J. 1998; 135:S77-89.

112. Topol EJ, Byzova TV, Plow EF. Platelet GPIIb/IIIa blockers. Lancet. 1999; 353:227-31.

113. Braunwald E, Antman EM, Beasley JW et al. ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina). J Am Coll Cardiol. 2000; 36:970-1062.

117. Enhanced Suppression of the Platelet IIb/IIIa receptor with Integrelin Therapy (ESPRIT) Investigators. Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial. Lancet. 2001; 356:2037-44.

118. O’Shea JC, Hafley GE, Greenberg S et al. Platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention: the ESPRIT trial: a randomized controlled trial. JAMA. 2001; 285:2468-73.

124. Goodman S. Enoxaparin and glycoprotein IIb/IIIa inhibition in non-ST-segement-elevation acute coronary syndrome: insights for the INTERACT trial. Am Heart J. 2005; 149:S73-80.

125. James S, Armstrong P, Califf R et al. Safety and efficacy of abciximab combined with dalteparin in the treatment of acute coronary syndromes. Eur Heart J. 2002; 23:1538-45.

126. Goodman SG, Fitchett D, Armstrong P et al. Randomized evaluation of the safety and efficacy of enoxaparin versus unfarctionated heparin in high-risk patients with non-ST-sgement elevation acute coronary syndromes receiving the glycoprotein IIb/IIIa inhibitor eptifibatide. Circulation. 2003; 107:238-44.

128. Lansky AJ, Hochman JS, Ward PA et al. Percutaneous coronary intervention and adjunctive pharmacotherapy in women: a statement for healthcare professional from the American Heart Association. Circulation. 2005; 111:940-3.

132. Antman EM, Hand M, Armstrong PW et al. 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction. J Am Coll Cardiol. 2008; 51:210-47.

991. Wright RS, Anderson JL, Adams CD et al. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American Academy of Family Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2011; 57:e215-367.

994. Levine GN, Bates ER, Blankenship JC et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011; 58:e44-122.

995. Hamm CW, Bassand JP, Agewall S et al, for The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST -segment elevation of the European Society of Cardiology (ESC). ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2011; 32:2999-3054.

1016. Eikelboom JW, Hirsh J, Spencer FA et al. Antiplatelet drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e89S-119S.

1100. Amsterdam EA, Wenger NK, Brindis RG et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 130:e344-426.

HID. Trissel LA. Handbook on injectable drugs. 14th ed; Bethesda, MD: American Society of Health-System Pharmacists; 2007:631.