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The new direct oral anticoagulants (DOACs; 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:
Recurrent VTE occurred at a similar rate in patients treated with DOACs versus VKAs (2.0% and 2.2%), demonstrating noninferiority of DOACs.
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; smaller declines were observed in gastrointestinal bleeding.
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); no significant differences in recurrent VTEs were observed with DOACs versus VKAs in patients with deep venous thrombosis, pulmonary embolism, body weight ≥100 kg, or moderately impaired renal function (creatinine clearance, 30–49 mL/min).
Although more major bleeding occurred overall in patients with cancer, older age, and impaired renal function than in other subgroups, no difference in bleeding was observed with DOACs versus VKAs in those with cancer, and significantly less bleeding occurred with DOACs in the elderly (P=0.04) and in those with impaired renal function (P=0.05).
Van Es N et al. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: Evidence from phase 3 trials. Blood 2014 Sep 18; 124:1968. (http://dx.doi.org/10.1182/blood-2014-04-571232)
Comment
VKAs have a slow onset of action, require frequent monitoring and dose adjustments, and have diverse interactions with food and other drugs. Therefore, the arrival of the new oral anticoagulants is welcome. These agents have now been shown to be as effective as VKAs and are associated with less major bleeding. Their drawbacks include the lack of a specific antidote, contraindication in those with a creatinine clearance <30 mL/min, and increased cost. Still needed are clinical trials to determine if there are clinically significant differences among these new anticoagulants.