Argatroban for prevention and treatment of thromboembolism in heparin-induced thrombocytopenia

OBJECTIVE: TO review the pharmacology, pharmacokinetics, efficacy, adverse events, and cost of argatroban in the prevention and treatment of thromboem bolism in patients with heparin-induced thrombocytopenia (HIT). DATA SOURCES: A MEDLINE search (1980 to August 2000) of English-language li terature was conducted using the search term argatroban to identify pertine nt case reports, clinical trials, abstracts, and review articles. Additiona l reports were identified from the reference lists compiled in the literatu re reviewed, as well as from the manufacturer. DATA SYNTHESIS: Argatroban is a synthetic direct thrombin inhibitor indicat ed for parenteral use in the prevention and treatment of thromboembolism in patients with HIT. Its elimination half-life is approximately 40-50 minute s, and it is primarily eliminated by hepatic metabolism and biliary secreti on. Compared with historical controls, argatroban-treated patients with HIT or HIT with thrombosis (HITTS) experienced lower rates of the composite en d point of death, amputation, and new thrombosis. Dosing is initiated at 2 mug/kg/min and adjusted to maintain the activated partial thromboplastin ti me at 1.5-3 times the patient's baseline. In Japan, argatroban is approved for use in acute ischemic stroke and chronic peripheral occlusive disease. It has also been used as an alternative to unfractionated heparin (UFH) in patients with a history of HIT or MITTS undergoing percutaneous coronary in tervention and other procedures. Additionally, argatroban has been compared with UFH in patients with acute myocardial infarction who were receiving t hrombolytic therapy. Hemorrhage is the primary adverse event associated wit h argatroban. Argatroban increases the prothrombin time, making assessment of the intensity of warfarin therapy during concurrent administration more complex. CONCLUSIONS: The use of argatroban in patients with HIT and MITTS is associ ated with improvement in clinical outcomes compared with historical control s. Argatroban offers several practical advantages over other available agen ts with respect to dosing, monitoring, reversibility of effect with discont inuation of the drug, and cost.