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Background: Frequent monitoring of patients declined during the COVID-19 pandemic, harming patients with chronic diseases who critically needed correct monitoring. We evaluated the impact of the COVID-19 pandemic in patients with non-valvular atrial fibrillation (NVAF) receiving treatment with vitamin K antagonists (VKA) or non-vitamin K antagonist oral anticoagulants (NOAC) in clinical practice in Spain. Methods: This observational, retrospective study analyzed prevalent patients treated with NOAC/VKA on 14/03/2019 (pre-COVID-19 period) and 14/03/2020 (COVID-19 period), who were followed up to 12 months. The study also considered incident patients who started treatment with NOAC/VKA between 15/03/2019 and 13/03/2020 (pre-COVID-19 period) and from 15/03/2020 to 13/03/2021 (COVID-19 period). Demographic characteristics, comorbidities, effectiveness, treatment patterns, and healthcare resource utilization were considered. Results: Prevalent patients amounted to 12,336 and 13,342 patients, whereas 1,612 and 1,602 incident patients were included in the pre-COVID-19 and COVID-19 periods, respectively. Prevalent patients treated with VKA had more strokes, thromboembolism, and major bleeding compared to those receiving NOAC, particularly during the COVID-19 period. NOAC patients had a 12 % lower risk of death than those on treatment with VKA (Hazard ratio = 0.88 [95 % CI: 0.81 – 0.95], p = 0.033). In addition, VKA patients were less persistent after 12 months than NOAC patients (pre-COVID-19 period: 52.1 % vs. 78.9 %, p |