Argatroban, a direct thrombin inhibitor for heparin-induced thrombocytopaenia: present and future perspectives.
Heparin remains the most commonly used anticoagulant in the treatment of patients with acute vascular syndromes, including myocardial infarction, unstable angina and ischaemic stroke. However, heparin therapy is not always associated with a significant improvement of clinical outcomes, is linked with enhanced bleeding risk and can occasionally provoke the development of heparin-induced thrombocytopaenia, the most devastating complication of conventional therapy with unfractioned heparin. Understanding the key role of thrombin in clot formation and platelet activation has stimulated the development of a new class of drugs - direct thrombin inhibitors. The direct thrombin inhibitor argatroban has been known for decades. Similar to the unfractioned heparin, argatroban requires intravenous administration and activated partial prothrombin time-dependent dose adjustment; however, this pharmacological agent has a relatively short half-life that broadens its safety margins, as well as its low antigenic potential due to the small molecular weight of the compound. The efficacy of argatroban has been demonstrated among patients with acute coronary syndromes and stroke. However, this drug is currently approved by the FDA only for the treatment of patients with heparin-induced thrombocytopaenia. Indeed, in such patients, argatroban significantly improves clinical outcomes, and is associated with reduced mortality. Further clinical studies are needed to present more clinical evidence necessary to broad the indication spectrum of this agent.
Serebruany
Michael V
MV
HeartDrug Research Laboratories, Johns Hopkins University, 7600 Osler Drive, Suite 307, Towson, Maryland 21204, USA. heartdrug@aol.com
Malinin
Alex I
AI
Serebruany
Victor L
VL
D000818:Animals; D000991:Antithrombins / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D005544:Forecasting; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D010875:Pipecolic Acids / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*
D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban