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      Influence of the COVID-19 pandemic on patients receiving oral anticoagulants for the treatment of non-valvular atrial fibrillation

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          Graphical abstract

          Highlights

          • NOAC use increased during COVID-19, reducing the incidence of cardiovascular events, the mortality rate, and the risk of death in comparison to VKA.

          • Patients treated with NOAC were more persistent to the anticoagulant treatment than those receiving VKA.

          • NOAC patients also required fewer healthcare resources than patients receiving VKA, particularly during the COVID-19 period.

          Abstract

          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 < 0.001; COVID-19 period: 49.2 % vs. 80.3 %, p < 0.001), and required more healthcare visits and hospitalizations than those on treatment with NOAC.

          Conclusion

          Compared to VKA, NOAC seems to have reduced the incidence of severe events and the use of healthcare resources for NVAF, particularly during the pandemic.

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          Most cited references26

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          Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases

          R Deyo (1992)
          Administrative databases are increasingly used for studying outcomes of medical care. Valid inferences from such data require the ability to account for disease severity and comorbid conditions. We adapted a clinical comorbidity index, designed for use with medical records, for research relying on International Classification of Diseases (ICD-9-CM) diagnosis and procedure codes. The association of this adapted index with health outcomes and resource use was then examined with a sample of Medicare beneficiaries who underwent lumbar spine surgery in 1985 (n = 27,111). The index was associated in the expected direction with postoperative complications, mortality, blood transfusion, discharge to nursing home, length of hospital stay, and hospital charges. These associations were observed whether the index incorporated data from multiple hospitalizations over a year's time, or just from the index surgical admission. They also persisted after controlling for patient age. We conclude that the adapted comorbidity index will be useful in studies of disease outcome and resource use employing administrative databases.
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            Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.

            Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59-0·81 vs 0·93, 0·76-1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84-1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43-1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02-1·60; p=0·045). This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population. None. Copyright © 2014 Elsevier Ltd. All rights reserved.
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              2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS.

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                Author and article information

                Contributors
                Journal
                Int J Cardiol Heart Vasc
                Int J Cardiol Heart Vasc
                International Journal of Cardiology. Heart & Vasculature
                Elsevier
                2352-9067
                10 February 2024
                April 2024
                10 February 2024
                : 51
                : 101358
                Affiliations
                [a ]Cardiology Department, Hospital Universitario de Bellvitge (IDIBELL) and CIBERCV, 08907 Hospitalet del Llobregat, Spain
                [b ]Health Economics and Outcomes Research, Atrys Health, 28002 Madrid, Spain
                [c ]Bristol Myers Squibb, Madrid, Spain, 28050 Madrid, Spain
                [d ]Real World Evidence and Outcomes Research, Bristol Myers Squibb, 28050 Madrid, Spain
                [e ]Pharmacy Department, Hospital Universitario Son Espases, IdISBa, 07120 Palma de Mallorca, Spain
                Author notes
                [* ]Corresponding author at: C/ Príncipe de Vergara, 132, planta 1, 28002 Madrid, Spain. ihernandez@ 123456atryshealth.com
                Article
                S2352-9067(24)00024-1 101358
                10.1016/j.ijcha.2024.101358
                10869899
                b271ec20-0b68-412a-8480-de2852c9ca1c
                © 2024 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 12 December 2023
                : 23 January 2024
                : 4 February 2024
                Categories
                Original Paper

                atrial fibrillation,anticoagulants,covid-19
                atrial fibrillation, anticoagulants, covid-19

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