Efegatran
Also known as: efegatran sulfate, LY294468
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Summary
Efegatran (also known as efegatran sulfate or LY294468) is an investigational small‑peptide direct thrombin inhibitor developed for intravenous use. It has been studied as an adjunct to thrombolytic therapy in acute myocardial infarction and as a substitute for heparin in unstable angina, aiming to provide more predictable anticoagulation by inhibiting both free and clot‑bound thrombin.
Mechanism of Action
Efegatran binds directly to the active site of thrombin, forming a covalent adduct that blocks the enzyme’s ability to convert fibrinogen to fibrin and to activate platelets. By targeting both circulating and clot‑bound thrombin, it interrupts the final amplification step of the coagulation cascade, leading to prolonged activated partial thromboplastin time and reduced thrombus formation.
What the Research Shows
Early reviews highlighted efegatran as a low‑molecular‑weight direct thrombin inhibitor with potential advantages over heparin. Clinical trials in the late 1990s and early 2000s evaluated intravenous efegatran sulfate in patients with acute myocardial infarction receiving streptokinase or accelerated alteplase, and in unstable angina compared with heparin. Across four randomized studies (total n≈1,400), efegatran achieved dose‑dependent prolongation of coagulation tests and comparable major‑bleeding rates to heparin, but did not demonstrate superior early coronary patency, infarct size reduction, or mortality benefit. One trial noted a modestly faster time to reperfusion, while another reported more minor bleeding and a few cases of intracranial hemorrhage at higher doses.
Reported Benefits
Evidence shows that efegatran provides anticoagulant effects comparable to heparin, with stable activated partial thromboplastin time prolongation and no excess of major bleeding in most studies. Its ability to inhibit clot‑bound thrombin may theoretically reduce thrombotic rebound, and a faster time to reperfusion was observed in one trial, suggesting a possible modest procedural advantage.
Limitations of the Evidence
Randomized trials have not demonstrated clear clinical superiority over standard heparin‑based regimens; primary efficacy endpoints such as early artery patency, infarct size, and mortality were similar. Some studies reported higher rates of minor bleeding and isolated intracranial hemorrhages at higher doses. The drug remains investigational, with limited data on long‑term outcomes, optimal dosing, and oral bioavailability.
Safety Considerations
Across studies, major bleeding rates were similar between efegatran and heparin, but minor bleeding and thrombophlebitis occurred more frequently with efegatran. High‑dose regimens were associated with a few cases of intracranial hemorrhage. As a covalent thrombin inhibitor, efegatran may carry a risk of off‑target toxicity, and careful monitoring of coagulation parameters is advised when used experimentally.
How It Is Administered
Efegatran is formulated as a sulfate salt for intravenous infusion. Dosing regimens in clinical trials ranged from 0.105 to 1.2 mg·kg⁻¹·h⁻¹, typically administered continuously over 48–96 hours alongside thrombolytic agents and aspirin. The drug is supplied as a sterile solution for infusion.
Routes of Administration
Goals & Uses
- Anticoagulation during percutaneous coronary intervention (PCI)AnticoagulationModerate
- Anticoagulation in acute coronary syndromesCardiovascular / ThrombosisModerate
- Prevention of thrombus formationHematology / AnticoagulationModerate
Contraindications
- Recent intracranial surgery or hemorrhagic strokeNeurologicHigh
- Active major bleedingHemorrhagic RiskHigh
- Known hypersensitivity to efegatran or arginine-based peptidesImmunologicHigh
Adverse Effects
- Injection site reactionsLocalUncommon
- ThrombocytopeniaHematologicRareLow platelet count
- Bleeding / hemorrhageHematologicCommon
Drug Interactions
- Antiplatelet agents (aspirin, clopidogrel)Moderate
- Other anticoagulants (heparin, warfarin, LMWH)High
- Thrombolytics (alteplase, streptokinase)High
Population Constraints
- PregnancyReproductive SafetyRelative
- Hepatic impairmentOrgan FunctionRelative
- Renal impairmentOrgan ImpairmentRelative
- Elderly patientsAgeRelative
Regulatory Status
- European UnionUnapprovedNo marketing authorization granted. Not approved by EMA or predecessor agencies.
- United StatesUnapprovedPhase II/III clinical development conducted by Eli Lilly in the 1990s; never approved by FDA. Development discontinued.
- United KingdomUnapprovedNo regulatory approval. Not licensed in the UK.
Never received regulatory approval in the US, EU, or UK. Clinical development was discontinued following Phase II/III trial results. No current active IND or approved indication known.
Evidence & Sources
- Journal ArticleModerateVan Aken H, et al.2001-01-01T00:00:00.000000Z
- Journal ArticleModerateSanderson PE, Naylor-Olsen AM1998-01-01T00:00:00.000000Z
- Journal ArticleModerateFung AY, et al.1999-01-01T00:00:00.000000Z
- Journal ArticleModeratePRIME Investigators2002-01-01T00:00:00.000000Z
- Journal ArticleModerateAouizerate P, Guizard M2002-01-01T00:00:00.000000Z
- Journal ArticleModerateKlootwijk P, et al.1999-01-01T00:00:00.000000Z
Frequently Asked Questions
What type of drug is efegatran?
Efegatran is a small‑peptide direct thrombin inhibitor (a peptidomimetic) that is administered intravenously as a sulfate salt. It is investigational and not approved for routine clinical use.
How does efegatran differ from heparin?
Unlike heparin, which indirectly inhibits thrombin via antithrombin, efegatran binds directly—and covalently—to thrombin’s active site, allowing inhibition of both free and clot‑bound enzyme. This results in a more predictable anticoagulant effect but has not shown clear clinical advantage in trials.
What clinical evidence supports its use?
Four randomized trials have compared intravenous efegatran to heparin in acute myocardial infarction and unstable angina. The studies found comparable major‑bleeding rates and no significant improvement in early coronary patency or mortality, though one trial noted a faster reperfusion time.
What are the main safety concerns?
Major bleeding was similar to heparin, but efegatran was associated with more minor bleeding and occasional intracranial hemorrhage at higher doses. Its covalent binding raises potential for off‑target effects, so coagulation monitoring is essential in research settings.
How is efegatran administered?
In research protocols efegatran sulfate is given as a continuous intravenous infusion, with dose ranges from about 0.1 to 1.2 mg per kilogram per hour, usually for 48–96 hours together with thrombolytics and aspirin.
What is Efegatran?
Efegatran (also known as efegatran sulfate or LY294468) is an investigational small‑peptide direct thrombin inhibitor developed for intravenous use. It has been studied as an adjunct to thrombolytic therapy in acute myocardial infarction and as a substitute for heparin in unstable angina, aiming to provide more predictable anticoagulation by inhibiting both free and clot‑bound thrombin.
What is Efegatran used for?
Efegatran is educationally associated with: Anticoagulation during percutaneous coronary intervention (PCI), Anticoagulation in acute coronary syndromes, Prevention of thrombus formation. Educational only — not medical advice.
How is Efegatran administered?
Recorded routes of administration: Intravenous.
What are the potential side effects of Efegatran?
Reported adverse effects include: Injection site reactions, Thrombocytopenia, Bleeding / hemorrhage. This list is not exhaustive — consult a qualified clinician.
Who should avoid Efegatran?
Recorded contraindications: Recent intracranial surgery or hemorrhagic stroke, Active major bleeding, Known hypersensitivity to efegatran or arginine-based peptides. Consult a qualified clinician before use.