Underdosing of direct oral anticoagulants in patients with atrial fibrillation – prevalence, trends, predictors and clinical significance

Background: Direct oral anticoagulants (DOAC) serve as first line treatment for non-valvular atrial fibrillation (NVAF). Real world data suggests lack of adherence to guideline-directed dose reductions, resulting mostly in underdosing.
Objectives: To assess the prevalence of DOAC underdosing in NVAF patients, identify predictors for undertreatment, and to compare clinical outcomes of underdosed patients to those treated appropriately with a full dose.

Methods: We analyzed data from a registry consisting of 3709 patients with NVAF treated with DOACs. Patients were classified as underdosed if treated with reduced dose despite not fulfilling FDA criteria for dose reductions. Risk for Stroke, myocardial infarction, death, bleeding and a composite endpoint including all was compared between underdosed patients and those appropriately treated with a full dose.

Results: 1200 (30.7%) patients were inappropriately treated, 1093 (29.4%) underdosed and 107 (2.8%) overdosed. Age ≥80, creatinine ≥1.5 mg/dL and history of peripheral vascular disease were independently associated with increased risk for underdosing. Following adjustments there was no difference in the risk for stroke (HR 0.79, CI 95% CI 0.44-1.4; p=0.793), myocardial infarction (HR 1.51, 95% CI 0.67-3.36; p=0.314), death (HR 1.23, 95% CI 0.87-1.72; p=0.229), bleeding (HR1.47, 95% CI 0.73-2.95; p=0.276) or for the composite end point (HR 1.27, 95% CI 0.97-1.66; p=0.073) between appropriately dosed and underdosed patients.

Conclusions: Nearly one third of patients suffering from NVAF are underdosed. Underdosing was found to be noninferior to full dose treatment with respect to stroke prevention. It is possible that factors other than the FDA labeling could be addressed when considering DOAC without compromising on treatment efficacy.