Efficacy and safety of dabigatran etexilate: a narrative review

Dabigatran etexilate is a newly developed direct thrombin inhibitor. After oral administration, this novel anticoagulant drug has a predictable response, which allows fixed dose regimens without the need for routine laboratory monitoring. Dabigatran demonstrated to be at least as effective as the current standard of care in the primary and secondary prevention of several thromboembolic events, such as the prevention of venous thromboembolism after orthopaedic surgery, the acute and long-term treatment of deep vein thrombosis and pulmonary embolism, and the prevention of thromboembolic complications of atrial fibrillation. Dabigatran showed a favourable safety profile, causing less intracranial haemorrhages compared to warfarin. However, higher incidence of dyspepsia and gastrointestinal bleeding has been reported, probably due to the formulation of dabigatran containing a tartaric acid core. It is not clear whether the increased number of acute coronary syndrome, reported with the use of this thrombin inhibitor, might be due to an intrinsic property of dabigatran or to a protective effect of the comparator treatment with warfarin. In case of major bleeding events or urgent reversal, no specific antidote is available. Suggested measures include anticoagulant withdrawal, infusion of prothrombin complex concentrates, haemodialysis and administration of oral activated charcoal, in addition to haemostatic interventions and supportive care. Although laboratory monitoring is not necessary, the activated partial thromboplastin time and the thrombin clotting time may provide a qualitative measurement of dabigatran activity, while the dilute thrombin clotting time and the ecarin clotting time may provide a quantitative measurement. Dabigatran has been recently licensed by the European Medicine Agency for the prevention of venous thromboembolism in patients undergoing elective total hip or knee arthroplasty and for the treatment of patients with atrial fibrillation at moderate-high thromboembolic risk. This review will focus on the pharmacological properties of dabigatran and its efficacy and safety profile from the results of large randomized clinical trials