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

ABSTRACT

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.

KEYWORDS:

• Afib
• DOAC
• DVT
• inappropriate
• NOAC
• PE

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conception, design data interpretation, manuscript drafting and revising critical information and final version: L Slipczuk.

Conception, design and data interpretation: C Rodriguez; MJ Garcia; J Romero.

Design, data collection, analysis, interpretation, manuscript drafting and revising critical information: F Aguilar.

Data analysis, interpretation and manuscript drafting: K Lo.

Data collection and analysis: EE Quintero; RJ Torres; WA Hung; JC Albano; D Brito; I Alviz.

Supplementary material

Supplemental data for this article can be accessed here.