Eptifibatide
A cyclic peptide modelled on rattlesnake venom that stops platelets clumping, given intravenously in heart attacks and coronary stenting
Eptifibatide is a cyclic heptapeptide that blocks glycoprotein IIb/IIIa, the receptor platelets use to clump together; its active structure came from a rattlesnake-venom protein. Given intravenously, it reduced death or heart attack in acute coronary syndromes and complications of coronary stenting, at the cost of more bleeding. FDA approved it as Integrilin in 1998; generics are sold.
What is it?
Platelets clump when fibrinogen links them through glycoprotein IIb/IIIa, a receptor found only on platelets and their precursors. Eptifibatide occupies that receptor. It is a small cyclic peptide whose active structure came from barbourin, a receptor blocker in the venom of the southeastern pigmy rattlesnake, and it is given intravenously as a bolus and infusion, with a plasma half-life of about 2.5 hours.
Three large trials established it. In PURSUIT, among 10,948 patients with acute coronary syndromes, death or heart attack at 30 days fell from 15.7% to 14.2%, with more bleeding but no more haemorrhagic strokes. In ESPRIT, during planned stenting, events fell from 10.5% to 6.6% and the trial stopped early for efficacy. IMPACT-II, earlier, tested it during coronary intervention.
Against tirofiban, the other small-molecule IIb/IIIa blocker, pooled trials found similar efficacy and a little less minor bleeding. In primary PCI, a bolus alone performed like the bolus plus infusion for bleeding and ischaemic events. In one small randomised trial of patients with unstable coronary disease who needed urgent bypass surgery, giving it beforehand was linked to fewer major events at a year without more surgical bleeding.
Stroke was the hoped-for new indication and did not deliver. The MOST trial in 2024 found no benefit from adding it to clot-busting treatment, and in patients given thrombolysis without thrombectomy there was only a 2.5% chance it beat placebo. A small pilot in septic shock explored its effect on blood vessel lining without changing practice.
FDA approved it as Integrilin on May 18, 1998; the brand is now discontinued and generics are sold. The dose is weight-based and halved for the infusion in reduced kidney function, given with aspirin and heparin, and the label asks for haemoglobin, platelet count, creatinine and clotting times before the first dose, with the aPTT kept between 50 and 70 seconds during medical management. The label warns of bleeding and of acute, profound thrombocytopenia, which needs the drug stopped at once.
Mechanism of Action
Eptifibatide is a cyclic peptide that blocks the platelet fibrinogen receptor, stopping platelets from clumping.
Glycoprotein IIb/IIIa
Occupies the platelet receptor that fibrinogen uses to bridge platelets, the final common step in aggregation.
From snake venom
Its design came from barbourin, a IIb/IIIa blocker in pigmy rattlesnake venom.
Short-acting
Plasma half-life about 2.5 hours; steady state within 4 to 6 hours of bolus plus infusion (label 12.3).
Published Research
The trials and reviews behind eptifibatide, read from their PubMed abstracts.
PURSUIT: 10,948 patients with acute coronary syndromes
Eptifibatide reduced death or non-fatal heart attack at 30 days from 15.7% to 14.2% (P=0.04), a benefit seen by 96 hours and consistent in most subgroups except women. Bleeding was more common, with no increase in haemorrhagic stroke.
ESPRIT: planned coronary stenting
Stopped early for efficacy. The primary endpoint fell from 10.5% of 1,024 patients on placebo to 6.6% of 1,040 on eptifibatide (P=0.0015); major bleeding was infrequent but commoner with eptifibatide (1.3% against 0.4%).
IMPACT-II: coronary intervention
By 30 days, ischaemic events occurred in 11.4% on placebo and 9.2% on the lower-dose regimen (P=0.063), significant only in a treatment-received analysis; major bleeding did not increase.
MOST: added to thrombolysis in stroke
Among 514 stroke patients all given intravenous thrombolysis, neither argatroban nor eptifibatide improved 90-day function over placebo; symptomatic brain haemorrhage was similar.
Bolus only during primary PCI
In 330 patients having primary PCI, giving only the bolus or the bolus plus the infusion produced similar bleeding (major bleeding in one patient per group) and similar in-hospital death, ischaemic events and stent thrombosis.
MOST: thrombolysis without thrombectomy
In the 260 MOST patients treated with thrombolysis alone, there was only a 2.5% probability that adding eptifibatide was better than placebo on 90-day disability; no secondary outcome favoured it.
With iloprost in septic shock
In a 24-patient pilot, iloprost plus eptifibatide did not change the primary endothelial outcomes against placebo, though some markers of endothelial damage and platelet counts moved in favourable directions.
Before urgent bypass surgery
In high-risk patients with non-ST-elevation acute coronary syndromes needing urgent bypass surgery, a preoperative eptifibatide infusion was associated with fewer major cardiac and cerebrovascular events at one year (14% against 35%) and fewer perioperative heart attacks than placebo, with similar blood loss and transfusion.
Clinical pharmacology
Glycoprotein IIb/IIIa binding of fibrinogen is the final common pathway of platelet aggregation; eptifibatide's pharmacophore derives from barbourin, a snake-venom inhibitor.
Life-threatening thrombocytopenia
A case report and literature review describing rare, life-threatening thrombocytopenia caused by eptifibatide, a drug the authors note is usually well tolerated without major adverse effects.
Against tirofiban
Across 9 randomised trials of 1,256 patients with acute coronary syndromes, eptifibatide caused less minor bleeding than tirofiban (relative risk 0.61), with no significant difference in major cardiac events, major bleeding or thrombocytopenia.
Dosing Data
Eptifibatide is a hospital drug given intravenously as a weight-based bolus and infusion with aspirin and heparin; the infusion is halved when creatinine clearance is below 50 mL/min.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the label and the trials above.
Contraindications & Cautions
From the eptifibatide label; the cardiology team decides.
Legal Status
Eptifibatide is an approved hospital medicine in the US and the EU.
Frequently Asked Questions
?What is eptifibatide used for?
Treating acute coronary syndromes and preventing clotting during coronary intervention, including stenting. It is given intravenously in hospital, usually with heparin.
?Where does it come from?
Its active structure came from barbourin, a platelet-receptor blocker in the venom of the southeastern pigmy rattlesnake; the drug itself is synthetic.
?What is its main risk?
Bleeding, which was more common than with placebo in its trials. Rarely it causes a sudden, severe fall in platelets, which is why platelet counts are monitored.
?Is it still used?
Yes, as a generic. A trial in primary PCI found a bolus alone performed like bolus plus infusion for bleeding and ischaemic events.
?Does it help in stroke?
No. The MOST trial found no benefit from adding it to thrombolysis, including in patients who did not have thrombectomy.
References
- [fda-pi] Eptifibatide injection, US prescribing information (Avenacy). DailyMed version effective August 15, 2024; read September 30, 2026.
- [pubmed] "Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes." N Engl J Med, 1998;339(7):436-43. PMID: 9705684.
- [pubmed] "Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial." Lancet, 2000;356(9247):2037-44. PMID: 11145489.
- [pubmed] "Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. Integrilin to Minimise Platelet Aggregation and Coronary Thrombosis-II." Lancet, 1997;349(9063):1422-8. PMID: 9164315.
- [pubmed] Adeoye O, et al. "Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke." N Engl J Med, 2024;391(9):810-820. PMID: 39231343.
- [pubmed] Phillips DR, et al. "Clinical pharmacology of eptifibatide." Am J Cardiol, 1997;80(4A):11B-20B. PMID: 9291241.
- [pubmed] Pothineni NV, et al. "Eptifibatide-Induced Thrombocytopenia--When Inhibitor Turns Killer." Am J Ther, 2016;23(1):e298-9. PMID: 24368608.
- [fda] FDA. Drugs@FDA (openFDA): Integrilin NDA 020718, approved May 18, 1998, discontinued; 15 eptifibatide applications. Read September 30, 2026.
- [other] European Medicines Agency. Medicines register: Eptifibatide Accord, authorised January 11, 2016; Integrilin, authorised July 1, 1999, withdrawn. Read September 30, 2026.
- [pubmed] Zhou X, et al. "Efficacy and safety of eptifibatide versus tirofiban in acute coronary syndrome patients: A systematic review and meta-analysis." J Evid Based Med, 2017;10(2):136-144. PMID: 28449419.
- [clinical-trial] Mousavi M, et al. "A Double-Blinded Randomized Controlled Trial Comparing Eptifibatide Bolus Only Versus Bolus Plus Infusion In Patients Undergoing Primary Percutaneous Coronary Intervention For ST-Elevation Myocardial Infarction." Cardiovasc Revasc Med, 2023;51:1-7. PMID: 36737382.
- [clinical-trial] Roy A, et al. "Thrombolysis Alone vs With Argatroban or Eptifibatide: A Prespecified Subgroup Analysis of the MOST Trial." Neurology, 2025;105(9):e214228. PMID: 41071964.
- [clinical-trial] Berthelsen RE, et al. "Co-administration of iloprost and eptifibatide in septic shock (CO-ILEPSS)-a randomised, controlled, double-blind investigator-initiated trial investigating safety and efficacy." Crit Care, 2019;23(1):301. PMID: 31488213.
- [fda-pi] Eptifibatide injection US prescribing information (Eugia US; DailyMed set 00ad7bbe, effective January 4, 2024), sections 2.1-2.3; read through openFDA October 6, 2026.
- [pubmed] Wilczynski M, et al. "Eptifibatide infusion versus placebo in high risk patients with non-ST segment elevation acute coronary syndromes managed with urgent coronary artery bypass graft surgery. A prospective multicenter randomized placebo-controlled clinical trial." J Cardiovasc Surg (Torino), 2016;57(1):100-10. PMID: 26771733.
Sources & Citations
Studies were read from their PubMed abstracts; the label from DailyMed (Eugia, set 00ad7bbe, effective January 4, 2024) through openFDA, read October 6, 2026.
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