EMA Review of DOACs Concludes Risk–Benefit Remains Positive

Megan Brooks

March 27, 2020

There is no need to change the conditions for use of the direct oral anticoagulants (DOACs) apixaban (Eliquis), dabigatran etexilate (Pradaxa), and rivaroxaban (Xarelto) in Europe, the European Medicines Agency (EMA) has concluded based on real-world data from a study they commissioned.

The retrospective study was carried out in Denmark, France, Germany, Spain, the Netherlands, and the United Kingdom. It assessed the risk for serious bleeding with DOACs relative to vitamin K antagonists in patients with nonvalvular atrial fibrillation.

The study was proposed after a workshop held by the EMA on the use of DOACs and whether it would be possible to enhance the benefit–risk profile of the drugs by further reducing the risk of major bleeding while maintaining or improving the protection against thromboembolic events.

Data from the EMA-funded study show that the pattern of serious bleeding seen in patients taking DOACs was similar to that seen in the clinical trials used to approve the medicines, and described in the current product information.

"The data were not sufficient to allow robust conclusions to be drawn on comparisons between the three medicines," according to an EMA press release.

The benefit–risk balance "remains positive" for all three DOACs within the authorized indications and no change to the product information is warranted, it continues.

There was no strong evidence of a high level of nonadherence to the authorized use of the DOACs.

The study did show an increased risk of bleeding in patients older than 75 years. "Further studies are needed to explore the issue and to determine whether there are differences in risk between individual DOACs. The data were not sufficient to recommend dosage changes in this population," the release says.

The agency will ask the manufacturers of all three DOACs to do an analysis to determine whether modification of the dosing recommendations could be beneficial for older patients.

The results were reviewed by EMA's Committee for Medicinal Products for Human Use (CHMP), in consultation with EMA's Pharmacovigilance Risk Assessment Committee (PRAC), and were compared with data from other similar studies and in the published literature.


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