Off-label direct oral anticoagulants dosing in atrial fibrillation and venous thromboembolism is associated with higher mortality.

Background: Direct oral anticoagulants (DOAC) off-label use data is lacking. Our study aimed to assess the clinical outcomes in a racially mixed population treated for atrial fibrillation (AF) and venous thromboembolism (VTE).

Methods: We retrospectively evaluated six months of DOAC prescriptions for AF or VTE treatment. Prescriptions were classified as off-label or appropriate following FDA labeling. The off-label group was sub-classified as under or overdosing.

Results: Of the 1,087 DOAC prescriptions, 67% were for AF. African Americans and Caucasians were equally represented. There were 171 (16%) inappropriate prescriptions, with 106 (62%), being underdosed. The off-label group had a higher 30-day readmissions risk (OR = 1.69, 95% CI:1.11-2.54, p = 0.012) and 1-year all-cause mortality (OR = 1.90, 95% CI:1.02-3.37, p = 0.032). There was no difference in major bleeding (OR = 1.27, 95% CI:0.63-2.37, p = 0.480) or new thromboembolism (OR = 1.27, 95% CI:0.73-2.13, p = 0.369) between the groups. Underdosing carried a higher risk of new thromboembolism (OR = 3.15, 95% CI:1.09-9.15, p = 0.024).

Conclusions: One in every six patients received off-label DOACs dosing. Off-label use had increased 30-day readmissions and 1-year all-cause mortality. Underdosing was associated with a higher risk of new thromboembolism.