Treatment of Venous Thromboembolism With Dabigatran
Treatment of Venous Thromboembolism With Dabigatran
Purpose of review The first study on the treatment of venous thromboembolism (VTE) with dabigatran (RE-COVER) was published in 2009. Three additional phase III trials on acute VTE therapy and extended treatment were recently presented. This article reviews the data and, where applicable, compares them with other novel oral anticoagulants, particularly rivaroxaban, for which all phase III trials have been published.
Recent findings A twin study to RE-COVER (RE-COVER II) confirmed that dabigatran is not inferior to warfarin regarding efficacy and confers a lower risk for clinically relevant bleeding in the treatment of acute VTE for 6 months. Two studies on the extended treatment of VTE with dabigatran showed that the results for efficacy and safety can be extrapolated to another 16 months (mean) of treatment (RE-MEDY) and that dabigatran reduces the risk of recurrence by 90% compared with placebo (RE-SONATE). In the latter case, there is an increase of the risk for clinically relevant bleeding.
Summary Dabigatran offers an alternative to warfarin for treatment of VTE without a need for coagulation monitoring or dose adjustments. Management of patients with VTE could thereby be simplified. Extended treatment might be considered more often for patients at higher risk of recurrence.
A number of new anticoagulants have been entered into clinical trials during the past decade, but only a minority of those belonged to the class of direct thrombin inhibitors. The first orally available thrombin inhibitor was ximelagatran, which was evaluated for the treatment of acute venous thromboembolism (VTE) as well as for the extended treatment of VTE with promising results in terms of efficacy and risk of bleeding. The drug was withdrawn from the market and from all studies in 2006 due to liver toxicity. At that time, phase III trials with the next oral direct thrombin inhibitor, dabigatran etexilate, a prodrug of dabigatran, had already started. Comparisons in the planning of the trials on treatment of VTE with dabigatran as well as of the first results were made versus those of ximelagatran. At the time of writing this review, results from all the recently published phase III trials with the factor Xa inhibitor rivaroxaban have become available. The aim of this review is to discuss the data from the phase III trials with dabigatran for the initial or extended treatment of VTE. As the last three trials so far only have been presented as abstracts, most of the information is still embargoed. The published data will be discussed in the light of the corresponding results with rivaroxaban.
Abstract and Introduction
Abstract
Purpose of review The first study on the treatment of venous thromboembolism (VTE) with dabigatran (RE-COVER) was published in 2009. Three additional phase III trials on acute VTE therapy and extended treatment were recently presented. This article reviews the data and, where applicable, compares them with other novel oral anticoagulants, particularly rivaroxaban, for which all phase III trials have been published.
Recent findings A twin study to RE-COVER (RE-COVER II) confirmed that dabigatran is not inferior to warfarin regarding efficacy and confers a lower risk for clinically relevant bleeding in the treatment of acute VTE for 6 months. Two studies on the extended treatment of VTE with dabigatran showed that the results for efficacy and safety can be extrapolated to another 16 months (mean) of treatment (RE-MEDY) and that dabigatran reduces the risk of recurrence by 90% compared with placebo (RE-SONATE). In the latter case, there is an increase of the risk for clinically relevant bleeding.
Summary Dabigatran offers an alternative to warfarin for treatment of VTE without a need for coagulation monitoring or dose adjustments. Management of patients with VTE could thereby be simplified. Extended treatment might be considered more often for patients at higher risk of recurrence.
Introduction
A number of new anticoagulants have been entered into clinical trials during the past decade, but only a minority of those belonged to the class of direct thrombin inhibitors. The first orally available thrombin inhibitor was ximelagatran, which was evaluated for the treatment of acute venous thromboembolism (VTE) as well as for the extended treatment of VTE with promising results in terms of efficacy and risk of bleeding. The drug was withdrawn from the market and from all studies in 2006 due to liver toxicity. At that time, phase III trials with the next oral direct thrombin inhibitor, dabigatran etexilate, a prodrug of dabigatran, had already started. Comparisons in the planning of the trials on treatment of VTE with dabigatran as well as of the first results were made versus those of ximelagatran. At the time of writing this review, results from all the recently published phase III trials with the factor Xa inhibitor rivaroxaban have become available. The aim of this review is to discuss the data from the phase III trials with dabigatran for the initial or extended treatment of VTE. As the last three trials so far only have been presented as abstracts, most of the information is still embargoed. The published data will be discussed in the light of the corresponding results with rivaroxaban.