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

OBJECTIVE: To renew the pharmacology, pharmacokinetics, efficacy adverse events, and cost of argatroban in the prevention and treatment of thromboembolism in patients with heparin-induced thrombocytopenia (HIT). DATA SOURCES: A MEDLINE search (1980 to August 2000) of English-language literature was conducted using the search term argatroban to identify pertinent case reports, clinical trials, abstracts, and review articles. Additional reports were identified from the reference lists compiled in the literature reviewed, as well as from the manufacturer. DATA SYNTHESIS: Argatroban is a synthetic direct thrombin inhibitor indicated for parenteral use in the prevention and treatment of thromboembolism in patients with HIT. Its elimination half-life is approximately 40-50 minutes, and it is primarily eliminated by hepatic metabolism and biliary secretion. Compared with historical controls, argatroban-treated patients with HIT or HIT with thrombosis (HITTS) experienced lower rates of the composite end point of death, amputation, and new thrombosis. Dosing is initiated at 2 microg/kg/min and adjusted to maintain the activated partial thromboplastin time 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 HITTS undergoing percutaneous coronary intervention and other procedures. Additionally, argatroban has been compared with UFH in patients with acute myocardial infarction who were receiving thrombolytic therapy. Hemorrhage is the primary adverse event associated with 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 HITTS is associated with improvement in clinical outcomes compared with historical controls. Argatroban offers several practical advantages over other available agents with respect to dosing, monitoring, reversibility of effect with discontinuation of the drug, and cost.

Clinical use of new antithrombotic therapies for medical management of acute coronary syndromes.

Prevention and management of acute coronary syndromes (ACS) are focal points of interest among health care providers. Acute coronary syndromes is an all-encompassing term that refers to unstable angina, non-Q wave myocardial infarction, and Q wave myocardial infarction. These syndromes are usually the result of atherosclerotic plaque rupture leading to thrombus formation in a coronary artery. Heparin and aspirin are traditional antithrombotic treatments. They typically are administered with antiischemic therapies and often with fibrinolytic agents for patients with ST segment elevation associated with acute myocardial infarction. Although aspirin and heparin are important, they have significant limitations that have prompted development of newer antithrombotic approaches. Adenosine diphosphate inhibitors have been evaluated as either alternatives or adjunctive treatment to aspirin. Glycoprotein IIb-IIIa receptor inhibitors, low-molecular-weight heparins, and direct thrombin inhibitors have been studied as concurrent therapy with, or as alternatives to, heparin.

The management of hypercholesterolemia revisited.

Coronary artery disease (CAD) is the major cause of death in the United States. This disease places a large economic burden on society stemming from both loss of productivity and use of health care resources. The primary factor that has been extensively correlated with risk for CAD is elevated cholesterol levels. The lack of efficacy with dietary restriction alone and the limitations, adverse effects, and drug interactions associated with current lipid-lowering therapies have caused health care providers to search for safer and more efficacious agents.