Novel Anticoagulants in an Older and Frail Population with Atrial Fibrillation: the Effect of Inappropriate Dosing on Clinical Outcomes

Purpose: An individualized approach should be taken regarding the use of novel oral anticoagulants (NOAC) in frail and older patients with atrial fibrillation (AF). We hypothesized that there would be a high proportion of underdosed patients among an older and frail population, where bleeding risk is higher.

Methods: We retrospectively analyzed patients admitted to an Internal Medicine ward with a previous diagnosis of AF and discharged with a NOAC (n = 327). We compared survival and incidence of dosing-related events (stroke, systemic embolism, and major bleeding) at 1-year between inappropriately underdosed patients (dose reduction without a formal indication) and the rest of the population.

Results: A total of 167 patients (51%) received a reduced dose despite lacking formal criteria for dose reduction. Before adjustment, underdosed patients, in comparison with non-underdosed patients, had a higher mortality at 1 year (HR = 1.6, 95% CI 1.2-2.1, p = 0.003) and a higher combined stroke, systemic embolism, and major bleeding event rate at 1-year (HR = 3.2, 95% CI 1.3-8.0, p = 0.015). After adjustment, combined stroke, systemic embolism, and major bleeding event rate was higher in underdosed patients (HR 3.7, 95% CI 1.1-12.3, p = 0.030), but survival was not different in the adjusted model (HR 1.4, 95% CI 0.9-2.1, p = 0.110).

Conclusions: Underdosed patients have a significant survival disadvantage and this may be due to clinician prescription bias, since this difference does not remain after adjusting for confounders. Combined stroke, systemic embolism, and major bleeding event rate was higher in underdosed patients.