Argatroban in HIT type II and acute coronary syndrome.

Abstract

Prior to initiation of the ARG-911 and ARG-915 clinical trials, there was no optimal replacement for heparin anticoagulation in patients with heparin-induced thrombocytopenia (HIT) type II. These prospective, historical controlled studies were designed to determine the usefulness of argatroban, a direct thrombin inhibitor (DTI) that is not immunogenic and does not interact with heparin antibody, in answering this clinical need. Clinical outcomes (37-day period) for 568 argatroban-treated and 193 control patients demonstrated significantly reduced risks of the primary efficacy composite endpoint (all-cause death, all-cause amputation, new thrombosis) and the secondary endpoints (death due to thrombosis, new thrombosis) with argatroban. Argatroban patients also experienced a more rapid recovery of platelet count. Bleeding events were similar among both groups. It was concluded that argatroban anticoagulation, compared with historical controls, improves clinical outcomes without increasing bleeding risk in patients having HIT with or without thrombosis. Argatroban has since been approved in the US for both prophylaxis and treatment of thrombosis in patients with HIT. Argatroban has been used in percutaneous coronary interventions in patients with and without HIT, for peripheral vascular procedures in both large and small vessels in HIT patients, and as an adjunct to thrombolytic therapy for the treatment of AMI. Treatment success rates and the same or less bleeding was demonstrated with argatroban compared to heparin controls. These pilot studies suggest that argatroban will provide reliable anticoagulation during interventional procedures. A consistent safety profile of argatroban has been demonstrated in all studies to date. The main attributes of argatroban are its rapid onset of action, fast reversibility of its anticoagulant effect, inhibition of clot-bound thrombin, easily monitored by the aPTT and ACT and no dosage adjustment in renal-impaired individuals. These properties make argatroban a predictable and useful anticoagulant for HIT and non-HIT patients.

• Authors: Bruce E Lewis, Jeanine M Walenga
• Journal: Pathophysiology of haemostasis and thrombosis (Pathophysiol Haemost Thromb) Vol. 32 Suppl 3 Pg. 46-55 ( 2002) ISSN: 1424-8832 [Print] Switzerland
• PMID: 12811012 (Publication Type: Journal Article, Review)
• Copyright: Copyright 2002 S. Karger AG, Basel

Chemical References

• Anticoagulants
• Pipecolic Acids
• Sulfonamides
• Arginine
• argatroban

Topics

• Anticoagulants (therapeutic use)
• Arginine (analogs & derivatives)
• Cardiac Surgical Procedures
• Coronary Disease (drug therapy)
• Humans
• Myocardial Infarction (drug therapy)
• Pipecolic Acids (therapeutic use)
• Sulfonamides
• Thrombocytopenia (chemically induced, diagnosis, drug therapy)