Direct oral anticoagulant dose selection: Challenging cases

Direct oral anticoagulants (DOACs) are given in fixed doses without routine laboratory monitoring of their anticoagulant effect based on the results of pivotal phase III trials. In some of these trials, patients were randomly allocated to receive a higher or lower dose of a DOAC, whereas in others, most patients were given a standard dose and only a subset deemed to be at risk of drug accumulation was given a lower dose. Treatment guidelines recommend dosing DOACs according to the way that they were tested in the trials, but for some patients, the optimal dosing remains uncertain. One example is patients with atrial fibrillation who are thought to have an unacceptably high risk of bleeding but do not meet the guideline criteria for dose reduction. A second is patients with venous thromboembolism who have completed 3 to 6 months of anticoagulation and are eligible for extended treatment with a standard or reduced dose of DOAC. In this review, we present a case-based approach to DOAC dose selection in these two settings.