Novel anticoagulants in an older and frail population with atrial fibrillation: the effect of inappropriate dosing on cl

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RESEARCH PAPER

Novel anticoagulants in an older and frail population with atrial fibrillation: the effect of inappropriate dosing on clinical outcomes José Paulo Henriques Cabral Lopes de Almeida1   · Ana Sofia Martinho1 · Adriana Girão2 · Ivo Barreiro3 · James Milner1 · Maria João Vidigal Ferreira1,4 · Armando Carvalho2,4 · Rui Terenas Baptista1,4 · Lino Gonçalves1,4 Received: 13 February 2020 / Accepted: 3 June 2020 © European Geriatric Medicine Society 2020

Key summary points Aim  To evaluate the proportion of patients underdosed (prescribed a reduced dose despite lack of indication) with a novel oral anticoagulant (NOAC) in an older and frail population with atrial fibrillation (AF). Findings  Around half (51%) of patients received a reduced dose despite lacking formal criteria for dose reduction. Adjusted combined stroke, systemic embolism and major bleeding event rate was higher in underdosed patients, but not adjusted survival. Message  A very significant proportion of frail and older patients with AF remains under an inappropriately reduced-dosed NOAC, and these patients have a worse prognosis. Abstract 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. * José Paulo Henriques Cabral Lopes de Almeida [email protected] 1



Department of Cardiology, Coimbra University Hospital, Coimbra, Portugal

2



Department of Medicine, Coimbra University Hospital, Coimbra, Portugal

3

Department of Medicine, Figueira da Foz Hospital, Figueir