As the only oral anticoagulation option available in the United States,
warfarin use remains widespread. However, concerns of safety remain a substantial issue. Additional anticoagulation options include
unfractionated heparin, low-molecular-weight heparins (e.g.,
enoxaparin,
dalteparin, and
tinzaparin), and the indirect-acting
factor Xa inhibitor,
fondaparinux.
Direct thrombin inhibitors represent a newer class of
anticoagulants used primarily in the treatment of
heparin-induced
thrombocytopenia and
percutaneous coronary interventions. Three intravenous agents are currently available-
lepirudin,
bivalirudin, and
argatroban-with an oral agent,
dabigatran etexilate, undergoing clinical investigation.
Dabigatran etexilate offers a rapid onset of action after
oral administration, reaching peak plasma concentrations and onset of
anticoagulant effect within 0.5-2 hours after administration. Studies have demonstrated linear pharmacokinetics, a linear relationship between
ecarin clotting time and international normalized ratio, and no known clinically significant
drug or food interactions.
Dabigatran etexilate has been studied in clinical trials as prophylaxis for
venous thromboembolism in patients undergoing
total knee replacement or
total hip replacement surgeries, as well as for
stroke prevention in patients with
atrial fibrillation.
Dabigatran etexilate has demonstrated superiority and noninferiority to
enoxaparin as prophylaxis for
venous thromboembolism in patients undergoing
orthopedic surgery, with the most frequent adverse effects being gastrointestinal complaints. Elevations in
alanine aminotransferase concentrations were noted in small percentages of patients in both the
dabigatran etexilate and
enoxaparin groups, with no observed dose association. The overall rates of major
bleeding were low, with minor
bleeding commonly noted, often at surgical sites. Clinical trials of
dabigatran etexilate in patients with
atrial fibrillation are ongoing. Results of short-term efficacy and safety appear promising. Further research is needed regarding long-term safety and efficacy for other anticoagulation indications.