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

Abstract

Background Direct oral anticoagulants (DOAC) are widely used in our practice. Data on inappropriate DOAC dosing in atrial fibrillation (AF), and venous thromboembolism (VTE) treatment is lacking. Our study aimed to assess the frequency, patterns and clinical outcomes in a racially mixed population. Methods We retrospectively evaluated 1,087 DOAC prescriptions for AF or VTE treatment in six months. Prescriptions were classified as either off-label or appropriate following FDA labeling. The off-label group was subclassified as under or overdosing according to the recommended daily dose. Results Most prescriptions (67%) were for AF. African American and Caucasian patients were equally represented (45% each). There were 171 inappropriate prescriptions (16%), with the majority, 106 (62%), being underdosed. There was a significantly 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) in the off-label group. There was no significant difference between major bleeding (OR=1.27, 95% CI:0.63-2.37, p=0.480) or new thromboembolic event (OR=1.27, 95% CI:0.73-2.13, p=0.369) based on dose appropriateness. However, underdosing was associated with higher risk of new thromboembolic events (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 dosing was associated with increased 30-day readmissions and 1-year all-cause mortality.