The new direct target-specific oral anticoagulants (TSOACs; dabigatran, rivaroxaban, apixaban, and edoxaban) have been compared with vitamin K antagonists (VKAs; warfarin and similar agents) for acute venous thromboembolism (VTE) in six recent phase III clinical trials encompassing more than 27,000 patients.
To determine the efficacy and safety of DOACs versus VKAs, investigators from the Netherlands and Canada performed a meta-analysis of those six trials and reported the following results:
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Recurrent VTE occurred at a similar rate in patients treated with DOACs versus VKAs
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DOACs were associated with a 39% relative reduction in major bleeding versus VKAs (P=0.002), with significant decreases in intracranial bleeding, fatal bleeding, and clinically relevant nonmajor bleeding.
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In subgroup analyses, fewer recurrent VTEs occurred with DOACs versus VKAs in older patients (age, ≥75; P=0.003) and in those with cancer (P=0.02).
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Although more major bleeding occurred overall in patients with cancer, older age, and impaired renal function than in other subgroups, no difference in overall bleeding was observed with DOACs versus VKAs in those with cancer, in the elderly (P=0.04) and in those with impaired renal function (P=0.05).
Comment:
The new TSOACs appear to be as effective as warfarin for the treatment of acute VTE with less major bleeding overall. However, these agents do not have a true antidote, are contraindicated with CrCl <30 mL/min and should be used with caution in the elderly.
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