Dabigatran for the prevention and treatment of thromboembolic disorders

Abstract

Dabigatran, an oral direct thrombin inhibitor, was the first of a new class of drugs referred to as non-vitamin K oral anticoagulants. Dabigatran is better than warfarin for stroke prevention in non-valvular atrial fibrillation (dose of 150 mg twice a day), non-inferior to enoxaparin for venous thromboembolism prevention after orthopedic surgery and non-inferior to warfarin in preventing recurrence after acute venous thromboembolism. The safety profile is similar to standard anticoagulants, with significant reduction observed in intracranial hemorrhage. Other advantages include a rapid onset of action and a predictable pharmacokinetic profile, allowing a fixed-dose regimen without the need for routine anticoagulation monitoring. In the event of bleeding, general support measures are recommended and if severe, the use of non-specific hemostatic agents such as prothrombin complex concentrates and recombinant factor VIIa must be considered. A specific reversal agent (idarucizumab) is in development.

Keywords:

• dabigatran
• new oral anticoagulants
• NOACs
• warfarin

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Dabigatran is an oral direct thrombin inhibitor that affects both free and clot-bound thrombin.

• Dabigatran has several advantages over warfarin and shows a superior benefit-to-risk profile.

• Phase III clinical trials support the indication of dabigatran for prevention of stroke in atrial fibrillation, venous thromboembolism prophylaxis after hip or knee replacement and long-term treatment of venous thromboembolism.

• Routine laboratory monitoring is not required, but it may be useful in certain circumstances.

• The gold standard for measurement of dabigatran levels is liquid chromatography with tandem mass spectrometry; however, in clinical practice, functional coagulation tests such as Hemoclot Thrombin Inhibitors and ecarin clotting time are the methods of choice.

• Dabigatran should be used with caution in patients with creatinine clearance <30 ml/min and is contraindicated in those with creatinine clearance <15 ml/min.

• Management of bleeding complications includes general support measures and use of non-specific hemostatic agents such as prothrombin complex concentrates and recombinant factor VIIa.

• A specific antidote for dabigatran (idarucizumab) has been developed and is currently under clinical investigation.