P4751Underdosing fragile patients - Are we helping or harming?

Abstract

Abstract Background An individualized approach should be taken regarding the utilization of direct oral anticoagulants (DOAC) in frail and elderly populations with atrial fibrillation (AF). We hypothesized that among an elderly and frail population, where the risk of bleeding, both real and perceived, is very high, the proportion of patients with a dose regimen different from the formal indication would be particularly high due to potential underdosing. Methods We conducted a retrospective, observational study enrolling 327 patients with AF admitted to an Internal Medicine ward during a 1-year period and discharged with a DOAC prescription. We divided the population in 2 groups: patients prescribed a reduced dose without formal dose reduction criteria (underdosed, n=170) and the rest of the population (n=157), which included adequately dosed patients, both with normal dose (n=99) and correctly reduced dose (n=43) and overdosed patients (n=15). A 1-year follow-up was completed for all patients, assessing the following outcomes: all-cause mortality, stroke, systemic embolism and major bleeding. Results Patients were elderly (81.9±7.68) and frail (Katz index 3.35±2.36). Apixaban was the most commonly prescribed NOAC (38.8%), followed by rivaroxaban (36.4%) and dabigatran (24.8%). Among underdosed patients, apixaban was prescribed in 45.3% of patients, dabigatran in 29.4% and rivaroxaban 25.3%. Although only 18.3% of patients had clinical criteria for dose reduction, 65.4% were discharged with reduced dose and thus 52% were underdosed. Regarding 1-year outcomes, mortality (40.8% vs 25.5%, RR=1.6, p=0.003) and the combined stroke, systemic embolism and major bleeding event rate (10.1% vs 3.2%, RR=3.16, p=0.015) were higher for underdosed patients. Among underdosed patients, comparing with the rest of the population, the increased ischemic events rate (ischemic stroke and systemic embolism) did not reached statistical significance (3.7% vs. 1.9%, p=0.5), but it did for hemorrhagic events (major bleeding and hemorrhagic stroke) (6.1% vs 0.6%, p=0.01) On multivariate analysis, even after considering adjustment for age, Katz and CHAD2VAS2C scores, renal function and DOAC prescribed, DOAC underdosing was associated with a higher risk of both ischemic and hemorrhagic events (HR = 3.51, 95% CI 1.08–11.38). However, it lost its independent negative effect regarding mortality (HR 1.32, 95% CI 0.87–1.99). Survival and event rate in underdosed Conclusions There is a significant proportion of frail and elderly patients with AF that are underdosed. This subset has a significant survival disadvantage, eventually reflecting prescription bias. However, underdosed patients have also a higher event rate of both ischemic and hemorrhagic events, suggesting that underdosing fragile patients is not an effective strategy and that instead it may be hazardous.