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the prevention of systemic embolisms&#44; is the cornerstone of treatment in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Oral anticoagulation &#40;OAC&#41; with vitamin K antagonists &#40;VKA&#41;&#44; reduces stroke incidence and maintains an acceptable bleeding risk compared to aspirin in patients at moderate to high thromboembolic risk&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Nevertheless&#44; in clinical trials&#44; direct-acting OAC &#40;DOAC&#41; demonstrated superiorrisk&#8211;benefit and cost-effectiveness profiles compared to VKA for AF patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;8</span></a> Consequently&#44; clinical guidelines advocate them as first-line medications for the prevention of embolic events in AF patients&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> except in those with mechanical prosthetic valve or moderate to severe mitral stenosis&#44; where DOAC are contraindicated due to poorer outcomes compared to VKA&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> Additionally&#44; real-life observational studies mostly favor DOAC over VKA&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#8211;14</span></a> However&#44; most of these studies rely on databases based on claims or International Classification of Diseases &#40;ICD&#41; codes&#44; which may not accurately reflect the clinical reality of OAC treatment for AF&#46; In this regard&#44; studies in the field of cardiology show that unstructured data from electronic health records &#40;EHR&#41; free-text can enhance population characterization and prognostic algorithms performance&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#8211;17</span></a> The use of data extracted from EHRs through natural language processing &#40;NLP&#41; and machine learning &#40;ML&#41; techniques could provide more accurate insights into the epidemiological aspects and clinical characteristics of AF patients receiving OAC in Spain&#46; To our knowledge&#44; no studies have used these techniques to assess OAC use in AF patients&#46; The present study is framed within the larger AFIRMA &#40;<span class="elsevierStyleItalic">AF In Real practice on Management of oral Anticoagulation&#41;</span> Study&#44; aimed at identifying the demographic and clinical characteristics of patients with AF who were prescribed DOAC and VKA&#44; including comparing the rates of effectivity and strategy-related outcomes between them&#46; In this study&#44; we aimed to estimate the prevalence of in-hospital AF in Spain and to describe the clinical characteristics and anticoagulant treatment patterns among patients with AF receiving OAC&#46; This analysis was based on data from EHRs of patients attended in 15 participating centers&#44; representative of various regions in Spain&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study design</span><p id="par0015" class="elsevierStylePara elsevierViewall">This multicenter&#44; retrospective study utilized RWD from EHRs across 15 Spanish hospitals from the National Healthcare Network including 8 country&#39;s regions &#40;Supplementary Table S1&#41;&#46; Data was gathered from all departments of each site during the study period&#44; from January 2014 to December 2020&#46; The sample size was determined by the most stringent objective of the AFIRMA study&#44; which was not addressed in this study &#40;comparison of effectivity rates between DOAC and VKA&#41;&#46; Accepting an alpha risk of 0&#46;95&#44; the precision achieved with the participants we included to determine the proportion of patients taking VKA and the proportion of individuals switching from acenocoumarol to apixaban&#44; were &#60;0&#46;3 and &#60;1&#46;2&#44; indicating a high level of accuracy in our findings&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study population</span><p id="par0020" class="elsevierStylePara elsevierViewall">Among all patients who attended the participating hospitals during the study period&#44; the study population included AF patients on OAC treatment reported in their EHRs&#46; Patients below 18 years&#44; with rheumatic mitral valvular disease &#40;major cause of mitral stenosis&#41; venous thromboembolism&#44; or pregnancy were excluded&#46; Patients were stratified by OAC type&#44; into VKA and DOAC and a retrospective cross-sectional analysis was conducted at the index date &#40;first time a patient met all inclusion criteria during the study period&#41;&#46; Treatment-related variables were analyzed during the follow-up period&#44; ranging from index date to the latest EHR within the study period&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Data source and extraction</span><p id="par0025" class="elsevierStylePara elsevierViewall">Clinical data from EHRs were gathered from outpatient clinics&#44; hospitalization&#44; discharge summaries&#44; and other reports across all departments of each participating site&#46; Both unstructured and structured data &#40;when available&#41; were extracted and analyzed using the EHRead&#174; technology described elsewhere&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> which uses NLP and ML techniques to convert free text from EHRs into a study database&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a> After that&#44; a descriptive analysis of demographic and clinical characteristics was performed&#46; The used terminology encompassed codes&#44; synonyms&#44; and definitions from clinical documentation&#44; based on SNOMED CT&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Further details on EHRead<span class="elsevierStyleItalic">&#174;</span> technology are provided in the Supplemental methods&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">EHRead&#174; performance was externally validated as previously described&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Briefly&#44; expert physicians from each hospital annotated a random selection of EHRs containing study variables to set a comparison standard&#46; These external annotations were compared with the variables detected by EHRead&#174; in the same EHRs corpus&#46; Further details regarding EHR performance evaluation and specific metrics obtained are shown in the Supplemental methods and Supplementary Table S2&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Study variables</span><p id="par0035" class="elsevierStylePara elsevierViewall">The study variables were extracted and analyzed as part of a curation process that guaranteed the quality and integrity of the data&#46; Data on sociodemographic variables such as age and sex were collected&#46; In addition&#44; clinical variables&#44; including comorbidities&#44; laboratory data&#44; and medications were recorded&#46; Of note&#44; these concepts and their definitions were retrieved to the extent they were registered in the included EHRs&#46; To reconstruct patient history&#44; all information before index &#40;including information stemming from EHRs dated before study period start&#44; if available&#41; was analyzed&#46; For variables analyzed around discrete time points&#44; the closest value to the time point &#40;within reference time windows&#41; was taken&#46; Reference time windows accounted for the variability in healthcare management between patients&#44; specialists&#44; and hospitals&#44; maximizing data retrieval from EHRs&#46; Time window ranges for each variable or group of variables are detailed in table footnotes&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Data analyses</span><p id="par0040" class="elsevierStylePara elsevierViewall">Categorical and binary variables are summarized by frequencies&#44; numerical variables by median&#44; quartile 1&#44; quartile 3 &#40;Q1&#44; Q3&#41;&#44; and available value counts&#46; Annual AF prevalence was calculated dividing the yearly AF cases by the at-risk population in hospital areas&#44; determined using public health service data and basic health zone spatial databases&#46; The at-risk population was estimated from National Institute of Statistics databases&#44; merging 2011 census tract spatial data with provincial population distribution from 1970&#8722;2021&#46; Prevalence calculations extended only to 2018 due to incomplete data for 2019&#8211;2020 from some sites&#46; The number of patients with evaluable data is shown in the analysis for discrete and continuous variables&#46; Binary variables like comorbidities or symptoms were considered absent if not recorded&#46; Multi-level categorical&#44; lifestyle factors&#44; and numeric variables were not imputed&#46; Analysis was performed using &#34;R&#34; software &#40;version 4&#46;0&#46;2&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Ethical considerations and study approval</span><p id="par0045" class="elsevierStylePara elsevierViewall">The study obtained ethical approval from national and local Ethics committees&#44; adhering to regional regulations and any protocol changes underwent review&#46; It complied with local laws&#44; the latest Declaration of Helsinki&#44; and Good Pharmacoepidemiology Practices&#46; Data from anonymized EHRs preserved patient confidentiality&#44; avoiding the need for individual consent&#46; Being a retrospective study and using RWD&#44; collection and variable evaluation were conducted blindly&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Study population and prevalence of AF</span><p id="par0050" class="elsevierStylePara elsevierViewall">During the study period&#44; a total of 4&#44;664&#44;224 patients were attended to the participating hospitals&#46; Within this source population&#44; 138&#44;773&#44;332 EHRs underwent processing by EHRead&#174;&#46; Throughout the study period&#44; AF average prevalence was 2&#46;5&#37; rising from 1&#46;9&#37; in 2014 to 2&#46;9&#37; in 2018&#46;In terms of age&#44; the prevalence increased progressively starting at below 1&#37; in patients under 50 years&#44; increasing to 3&#46;5&#37; among those aged 60&#8211;69&#44; further to 8&#37; in the 70&#8211;79 age group&#44; and peaking at 15&#37; among individuals aged 80 years and above &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> and Supplementary Table S3&#41;&#46; In the descriptive analysis&#44; 57&#44;190 patients were included&#44; 46&#44;143 &#40;80&#46;7&#37;&#41; on VKA and 11&#44;047 &#40;19&#46;3 &#37;&#41; receiving DOAC &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Demographic&#44; clinical characteristics and treatments</span><p id="par0055" class="elsevierStylePara elsevierViewall">The median age of patients was 78 &#40;Q1&#44; Q3 69&#44; 84&#41; years&#44; 78 &#40;70&#44; 84&#41; years in the VKA&#44; and 76 &#40;67&#44; 83&#41; years in the DOAC group&#46; Males were 53&#37; overall&#44; 52&#37; in VKA group&#44; and 56&#37; in DOAC group &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Cardiovascular comorbidities were common among participants&#46; In the VKA group&#44; hypertension &#40;76&#46;3&#37;&#41;&#44; diabetes mellitus &#40;48&#46;0&#37;&#41;&#44; and heart failure &#40;42&#46;2&#37;&#41; were frequent&#46; Additionally&#44; 64&#46;0 &#37; had a CHA2DS2-VASc Score &#8805; 4&#46; International normalized ratio &#40;INR&#41; values were documented in the free text of EHRs for 51&#46;5&#37; of VKA patients&#44; with a median of 1&#46;94 &#40;1&#46;2&#44; 2&#46;8&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; In the DOAC group&#44; hypertension was observed in 72&#46;1&#37;&#44; diabetes mellitus in 41&#46;6&#37;&#44; and heart failure in 36&#46;4&#37;&#46; Up to 52&#46;0&#37; of these patients had a CHA2DS2-VASc Score &#8805; 4 &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">When examining concomitant treatments among all patients&#44; beta-blockers were the most prevalent medication at baseline &#40;51&#46;2&#37;&#41;&#44; followed by diuretics &#40;45&#46;9&#37;&#41;&#44; statins &#40;37&#46;4&#37;&#41;&#44; Angiotensin-converting enzyme &#40;ECA&#41; inhibitors &#40;27&#46;7&#37;&#41;&#44; angiotensin II antagonists &#40;26&#46;5&#37;&#41;&#44; and acetylsalicylic acid &#40;18&#46;8&#37;&#41;&#46; For the VKA group&#44; 47&#46;9&#37; of the patients were on diuretics&#44; and 38&#46;1&#37; on statins&#46; In the DOAC group&#44; 37&#46;5&#37; were on diuretics&#44; and 34&#46;5&#37; on statins &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Switch of OAC treatment</span><p id="par0065" class="elsevierStylePara elsevierViewall">In the study&#44; 8561 &#40;15&#46;0&#37;&#41; patients changed their OAC treatment&#46; Dabigatran &#40;19&#46;7&#37;&#41; and warfarin &#40;40&#46;2&#37;&#41; were the most switched treatments in the DOAC and VKA groups&#46; The most prevalent switch among VKA to DOAC was from acenocoumarol to apixaban &#40;35&#46;2&#37;&#41;&#46; On the other hand&#44; in the DOAC group&#44; the most common switch was from any drug to acenocoumarol&#44; with rates ranging between 58&#46;6&#37; and 70&#46;2&#37;&#46; The median duration of OAC use prior to switching varied across formulations&#44; being 478 &#40;Q1&#44; Q3 144&#46;0&#44; 976&#46;7&#41; days for acenocoumarol &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">The AFIRMA study represents the first attempt to apply NLP and ML for extracting and analyzing RWD from patients with AF on OAC treatment&#46; Thanks to this novel approach&#44; we were able to obtain detailed data from a large cohort &#40;<span class="elsevierStyleItalic">N</span>&#8239;&#61;&#8239;55&#44;824&#41; including patients from 15 hospitals from 8 health regions in Spain&#46; This provides a comprehensive overview of the epidemiology&#44; clinical characteristics&#44; and real-world OAC prescription trends in AF patients&#46; Findings indicate that these patients are predominantly elderly with multiple comorbidities&#44; mainly cardiovascular&#44; increasing stroke risk and medication use&#44; highlighting a fragile&#44; complex profile&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Our investigation unveiled an average AF prevalence of 2&#46;5&#37;&#44; which notably escalates to 8&#46;0&#37; among patients aged 70&#8211;79 years and further to 15&#37; among those aged 80 years or older&#46; This pattern aligns with previous studies conducted within the Spanish population&#46; For instance&#44; one study encompassing 8343 individuals reported an overall prevalence of 4&#37;&#44; with a rise to 9&#46;3&#37; among those aged 70&#8211;79 and 17&#46;7&#37; for those over 80&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Similarly&#44; another study involving 17&#44;291 participants indicated an overall prevalence of 1&#46;4&#37;&#44; which increased to 6&#46;3&#37; among individuals aged over 75 years&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Our study found VKAs prescribed in 80&#46;7&#37; of cases and DOACs in 19&#46;3&#37;&#46; Despite DOACs&#39; superior risk-benefit and cost-effectiveness&#44;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;8&#44;22</span></a> Spanish health ministry recommendations during the study period restricted their use to specific AF cases&#44; such as VKA hypersensitivity&#44; previous intracranial bleeding&#44; stroke with high hemorrhage risk&#44; suboptimal VKA response&#44; or INR control&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">23</span></a> This likely resulted in DOACs being relegated to a second-line role&#44; influenced by economic constraints&#46; Demographically and clinically&#44; VKA patients were older with more comorbidities and higher CHA2DS2-VASc score than DOAC patients&#44; aligning with both Spanish and international findings&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;24</span></a> Reflecting their comorbidities&#44; 61&#46;0&#37; of our AF cohort had very high CHA2DS2-VASc Scores &#40;&#8805;4&#41;&#44; indicating a substantial stroke risk&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">25</span></a> These patterns&#44; alongside the mentioned restrictions&#44; suggest that despite the clinical data supporting DOACs&#39; safety and efficacy in older comorbid patients&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">26</span></a> regulatory limitations might influence their real-world prescription&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Analytically&#44; INR levels in the VKA group were often at the lower end of recommended ranges&#46; Guidelines advise an INR of 2&#46;0&#8211;3&#46;0 for AF patients to balance thromboembolic prevention and bleeding risks&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Our findings are consistent with prior studies focused on the Spanish population&#44; where 40&#37;-60&#37; of patients had suboptimal INR ranges&#44;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">27&#8211;30</span></a> correlating with increased ischemic events risk&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">31</span></a> Given these results&#44; diligent INR monitoring and adjustment are crucial to optimize therapy and reduce risks for these patients&#46; Moreover&#44; AF patients frequently received medications primarily for cardiovascular conditions &#40;hypertension&#44; dyslipidemia&#41; and diabetes&#46; Also&#44; many take aspirin or nonsteroidal anti-inflammatory drugs &#40;NSAIDs&#41;&#44; which are associated with a higher bleeding risk when combined with OAC&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">32</span></a> The polypharmacy observed previously in AF patients in about 40&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">30</span></a> should be seen as a health status indicator&#44; requiring strategies to minimize inappropriate prescribing due to its association with increased cardiovascular mortality risk&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">33</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">We examined patients changing OAC treatments&#44; being the most common switch from a DOAC to acenocoumarol&#46; Among those transitioning from VKA to DOAC&#44; the predominant change was from acenocoumarol to apixaban&#46; Research focuses on VKA to DOAC transitions&#44; revealing risks and benefits&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">34</span></a> However&#44; RWD is scarce&#46; In this context&#44; a European study over 3 years showed that 5&#46;4&#37; of patients switched from VKA to DOAC&#44; and 8&#46;6&#37; presented the reversed shift&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">35</span></a> In our study&#44; the primary switch was from DOAC to acenocoumarol&#44; possibly due to previously mentioned DOAC prescription restrictions&#46; Switching from VKA to apixaban corresponds with a systematic review showing rising preference for apixaban&#44; increasing from 19&#46;8&#37; &#40;2011&#8211;2013&#41; to 45&#37; in 2015 in Europe&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">34</span></a> This preference is likely linked to apixaban&#39;s superior safety and security profile compared to VKA&#44; as demonstrated in the ARISTOTLE study&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">36</span></a> Additionally&#44; the ARISTOPHANES study&#44; based on RWD&#44; showed a comparative advantage over other DOACs like dabigatran and rivaroxaban&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> While many studies in the literature don&#39;t extensively report reasons for switching from DOAC to VKA&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">34</span></a> Hohnloser et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">37</span></a> analyzed a German claims database of over 50&#44;000 patients&#44; identifying age &#40;&#62;65 years&#41; and clinical events &#40;stroke&#44; myocardial infarction&#44; gastrointestinal bleeding&#44; and cardioversion&#41; as factors for switching from DOAC to VKA&#46; Conversely&#44; transitions from VKA to DOAC were due to therapy convenience&#44; poor anticoagulation profile&#44; bleeding&#44; patient decision&#44; and poor adherence&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">34</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">This multicenter study&#39;s primary strength is its use of innovative technology to create a comprehensive dataset of Spanish AF patients on OAC&#44; the largest to date&#46; Furthermore&#44; this technology allowed for extracting key information from unstructured free-text&#44; not just from structured ICD-coded data as in previous real-life studies&#46; However&#44; this study has limitations&#46; Its retrospective&#44; RWD-based nature led to some variables&#44; like specific switching reasons&#44; not being analyzable due to lack of well-documented causal relationship in EHR&#46; Additionally&#44; results are influenced by the characteristics of the Spanish healthcare system&#44; including restricted DOAC&#46; Finally&#44; the data&#44; sourced exclusively from hospitals&#44; may not fully represent the broader population of AF patients on OAC in ambulatory settings&#44; potentially limiting the extrapolation of our findings to the general population&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In summary&#44; the AFIRMA study&#44; pioneering in using NLP and ML to deeply describe AF patients undertaking OAC in Spain&#44; reveals significant AF prevalence&#44; with age as a key factor&#46; It shows a preference for VKA over DOAC&#44; highlights high comorbidity&#44; especially cardiovascular&#44; and notes polypharmacy&#44; especially in VKA patients&#46; We observed that most patients maintained their initial anticoagulant&#44; but among switchers&#44; DOAC to acenocoumarol was most common&#44; with VKA switchers favoring apixaban&#46; Our extensive patient sample and detailed analysis offer valuable insights into AF management and OAC optimization&#46; Nonetheless&#44; additional research is imperative to fully understand these medications&#39; real-world safety and efficacy&#44; especially considering the differences between patients on VKA and DOAC&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflicts of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">JCS&#44; MA &#38; CS were paid consultants to Pfizer in connection with the development of this study&#46; CAC &#38; LMS are employees of CRO&#46; DA &#38; SFC are employees of Pfizer&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Funding</span><p id="par0110" class="elsevierStylePara elsevierViewall">This study was sponsored by <span class="elsevierStyleGrantSponsor" id="gs0005">Bristol Myers Squibb&#47; Pfizer Alliance</span>&#46;</p></span></span>"
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              "identificador" => "sec0055"
              "titulo" => "Demographic&#44; clinical characteristics and treatments"
            ]
            2 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Switch of OAC treatment"
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Discussion"
        ]
        9 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Conflicts of interest"
        ]
        10 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Funding"
        ]
        11 => array:2 [
          "identificador" => "xack763418"
          "titulo" => "Acknowledgments"
        ]
        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2024-04-24"
    "fechaAceptado" => "2024-05-18"
    "PalabrasClave" => array:2 [
      "en" => array:2 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1856919"
          "palabras" => array:8 [
            0 => "Atrial fibrillation"
            1 => "Oral anticoagulation"
            2 => "Vitamin K antagonists"
            3 => "Direct oral anticoagulants"
            4 => "Real-world evidence"
            5 => "Artificial intelligence"
            6 => "Natural language processing"
            7 => "Machine learning"
          ]
        ]
        1 => array:4 [
          "clase" => "abr"
          "titulo" => "Abbreviations"
          "identificador" => "xpalclavsec1856921"
          "palabras" => array:12 [
            0 => "AF"
            1 => "AI"
            2 => "DOAC"
            3 => "EHR"
            4 => "ICD"
            5 => "INR"
            6 => "ML"
            7 => "NLP"
            8 => "NSAIDs"
            9 => "OAC"
            10 => "RWD"
            11 => "VKA"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1856920"
          "palabras" => array:8 [
            0 => "Fibrilaci&#243;n auricular"
            1 => "Anticoagulaci&#243;n oral"
            2 => "Antagonistas de la vitamina K"
            3 => "Anticoagulantes orales directos"
            4 => "Evidencia en el mundo real"
            5 => "Inteligencia artificial"
            6 => "Procesamiento del lenguaje natural"
            7 => "Aprendizaje autom&#225;tico"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Oral anticoagulation &#40;OAC&#41; is key in atrial fibrillation &#40;AF&#41; thromboprophylaxis&#44; but Spain lacks substantial real-world evidence&#46; We aimed to analyze the prevalence&#44; clinical characteristics&#44; and treatment patterns among patients with AF undertaking OAC&#44; using natural language processing &#40;NLP&#41; and machine learning &#40;ML&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">This retrospective study included AF patients on OAC from 15 Spanish hospitals &#40;2014&#8211;2020&#41;&#46; Using EHRead&#174; &#40;including NLP and ML&#41;&#44; and SNOMED&#95;CT&#44; we extracted and analyzed patient demographics&#44; comorbidities&#44; and OAC treatment from electronic health records&#46; AF prevalence was estimated&#44; and a descriptive analysis was conducted&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Among 4&#44;664&#44;224 patients in our cohort&#44; AF prevalence ranged from 1&#46;9&#37; to 2&#46;9&#37;&#46; A total of 57&#44;190 patients on OAC therapy were included&#44; 80&#46;7&#37; receiving Vitamin K antagonists &#40;VKA&#41; and 19&#46;3&#37; Direct-acting OAC &#40;DOAC&#41;&#46; The median age was 78 and 76 years respectively&#44; with males constituting 53&#37; of the cohort&#46; Comorbidities like hypertension &#40;76&#46;3&#37;&#41;&#44; diabetes &#40;48&#46;0&#37;&#41;&#44; heart failure &#40;42&#46;2&#37;&#41;&#44; and renal disease &#40;18&#46;7&#37;&#41; were common&#44; and more frequent in VKA users&#46; Over 50&#37; had a high CHA2DS2-VASc score&#46; The most frequent treatment switch was from DOAC to acenocoumarol &#40;58&#46;6&#37; to 70&#46;2&#37;&#41;&#46; In switches from VKA to DOAC&#44; apixaban was the most chosen &#40;35&#46;2&#37;&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Utilizing NLP and ML to extract RWD&#44; we established the most comprehensive Spanish cohort of AF patients with OAC to date&#46; Analysis revealed a high AF prevalence&#44; patient complexity&#44; and a marked VKA preference over DOAC&#46; Importantly&#44; in VKA to DOAC transitions&#44; apixaban was the favored option&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Materials and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">La anticoagulaci&#243;n oral &#40;ACO&#41; es clave en la tromboprofilaxis de la fibrilaci&#243;n auricular &#40;FA&#41;&#44; pero Espa&#241;a carece de evidencia relevante en el mundo real&#46; Nuestro objetivo fue analizar la prevalencia&#44; las caracter&#237;sticas cl&#237;nicas y los patrones de tratamiento en pacientes con FA en tratamiento con ACO&#44; utilizando el procesamiento del lenguaje natural &#40;PLN&#41; y el aprendizaje autom&#225;tico &#40;ML&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio retrospectivo en pacientes con FA en tratamiento con ACO de 15 hospitales espa&#241;oles &#40;2014&#8211;2020&#41;&#46; Utilizando EHRead&#174; &#40;incluyendo PNL y ML&#41;&#44; y SNOMED&#95;CT&#44; extrajimos y analizamos los datos demogr&#225;ficos de los pacientes&#44; las comorbilidades y el tratamiento con ACO de las historias cl&#237;nicas electr&#243;nicas&#46; Se estim&#243; la prevalencia de FA y se realiz&#243; un an&#225;lisis descriptivo&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">De los 4&#46;664&#46;224 pacientes de nuestra cohorte&#44; la prevalencia de FA oscil&#243; entre el 1&#44;9&#37; y el 2&#44;9&#37;&#46; Se incluyeron un total de 57&#46;190 pacientes en tratamiento con ACO&#44; de los cuales el 80&#44;7&#37; recib&#237;a antagonistas de la vitamina K &#40;AVK&#41; y el 19&#44;3&#37; ACO de acci&#243;n directa &#40;ACOD&#41;&#46; La mediana de edad fue de 78 y 76 a&#241;os&#44; respectivamente&#44; y los varones constituyeron el 53&#37; de la cohorte&#46; Las comorbilidades como hipertensi&#243;n arterial &#40;76&#44;3&#37;&#41;&#44; diabetes &#40;48&#44;0&#37;&#41;&#44; insuficiencia card&#237;aca &#40;42&#44;2&#37;&#41; y enfermedad renal &#40;18&#44;7&#37;&#41; fueron frecuentes y m&#225;s frecuentes en los usuarios de AVK&#46; M&#225;s del 50&#37; ten&#237;a una puntuaci&#243;n alta de CHA2DS2-VASc&#46; El cambio de tratamiento m&#225;s frecuente fue de ACOD a acenocumarol &#40;58&#44;6&#37; a 70&#44;2&#37;&#41;&#46; En los cambios de AVK a ACOD&#44; apixab&#225;n fue el m&#225;s elegido &#40;35&#44;2&#37;&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Utilizando PNL y ML para extraer la RWD&#44; establecimos la cohorte espa&#241;ola m&#225;s completa de pacientes con FA tratados con ACO hasta la fecha&#46; El an&#225;lisis revel&#243; una alta prevalencia de FA&#44; complejidad de los pacientes y una marcada preferencia por AVK sobre el ACOD&#46; Es importante destacar que&#44; en las transiciones de AVK a ACOD&#44; apixab&#225;n fue la opci&#243;n preferida&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Material y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0130" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0090"
          ]
        ]
      ]
    ]
    "multimedia" => array:6 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1755
            "Ancho" => 2508
            "Tamanyo" => 224928
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patients flow-chart&#46; Abbreviations&#58; EHRs&#44; electronic health records&#59; AF&#44; atrial fibrillation&#59; OAC&#44; oral anticoagulants&#59; VKAs&#44; vitamin K antagonist&#59; DOACs&#58; Direct oral anticoagulants&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2615
            "Ancho" => 2508
            "Tamanyo" => 258219
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        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estimate prevalence of AF by age&#46; Of note&#44; the yearly incidence was estimated until 2018 to include patient follow-up data from all participating sites&#46; The at-risk population considered for calculating AF prevalence each year was as follows&#58; 2014&#58; 3&#44;194&#44;788&#59; 2015&#58; 3&#44;208&#44;773&#59; 2016&#58; 4&#44;513&#44;867&#59; 2017&#58; 5&#44;202&#44;572&#59; and 2018&#58; 3&#44;767&#44;266&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Table "
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          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">All the variables included in this table were extracted from free-text&#44; and thus their frequencies are contingent upon the extent of their documentation in EHRs&#46; Abbreviations&#58; VKA&#44; vitamin K antagonist&#44; DOAC&#44; direct-acting oral anticoagulants&#44; IQR&#44; interquartile range&#59; INR&#58; International Normalized Ratio&#46;</p>"
          "tablatextoimagen" => array:1 [
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                0 => """
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Overall &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;57&#44;190&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">VKA &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;46&#44;143&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">DOAC &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;11&#44;047&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Age&#44; years&#44; median&#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78 &#40;69&#44; 84&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78 &#40;70&#44; 84&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">76 &#40;67&#44; 83&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Male sex&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">30&#44;110&#40;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#44;908 &#40;52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6202 &#40;56&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Comorbidities&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#44;655 &#40;76&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#44;687 &#40;77&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7968 &#40;72&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Heart failure&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">24&#44;150 &#40;42&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#44;124 &#40;43&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4026 &#40;36&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#44;452 &#40;48&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#44;857 &#40;49&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4595 &#40;41&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Renal disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;669 &#40;18&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9022 &#40;19&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1647 &#40;14&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Coronary disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5911 &#40;10&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4910 &#40;10&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1001 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pulmonary disease&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5909 &#40;10&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4974 &#40;10&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">935 &#40;8&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Transient ischemic attack&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3282 &#40;5&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2642 &#40;5&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">640 &#40;5&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Myocardial infarction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2302 &#40;4&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1891 &#40;4&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">411 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hemodialysis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">828 &#40;1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">782 &#40;1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">46 &#40;0&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">CHA2DS2-VASc Score<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">23&#44;769 &#40;41&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Median &#40;Q1&#44; Q3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
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                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">CHA2DS2-VASc Score&#58; Congestive heart failure&#44; Hypertension&#44; Age &#8805; 75&#44; Diabetes mellitus&#44; Stroke or transient ischemic attack&#44; Vascular disease&#44; Age 6&#8722;74 years&#44; Sex category Score&#46;</p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">INR&#8239;&#62;&#8239;15 has been discarded in the analysis for considering outliers&#46; Time window &#40;first report&#44; inclusion date&#93;&#44; except to INR&#58; Inclusion date &#91;&#8722;180d&#44; &#43;30d&#93;&#46;</p>"
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        "tipo" => "MULTIMEDIATABLA"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Overall &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;57&#44;190&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">VKA &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;46&#44;143&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">DOAC &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;11&#44;047&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antihypertensive agents&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Beta blockers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#44;300 &#40;51&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#44;280 &#40;50&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6020 &#40;54&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diuretics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#44;250 &#40;45&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#44;112 &#40;47&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4138 &#40;37&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ACE inhibitors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;813 &#40;27&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;311 &#40;28&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2502 &#40;22&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Angiotensin II antagonists&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;189 &#40;26&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;223 &#40;26&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2966 &#40;26&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antidiabetic agents&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#44;983 &#40;43&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#44;894 &#40;43&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4089 &#40;37&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lipid-lowering drugs&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Statins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#44;397 &#40;37&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#44;591 &#40;38&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3806 &#40;34&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fibrates&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1551 &#40;2&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1353 &#40;2&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">198 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Resines<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">107 &#40;0&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85 &#40;0&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;0&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ezetimiba&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1075 &#40;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">845 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">230 &#40;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antiplatelet treatment&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acetilsalicilic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">10&#44;694 &#40;18&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">8608 &#40;18&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">2086 &#40;18&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Clopidogrel&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2878 &#40;5&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">2317 &#40;5&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">561 &#40;5&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Others<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">834 &#40;1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">677 &#40;1&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">157 &#40;1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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            0 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Included references to&#58; Abciximab&#44; cilostazol&#44; dipyridamole&#44; epoprostenol&#44; eptifibatide&#44; iloprost&#44; prasugrel&#44; ticagrelor&#44; ticlopidine&#44; triflusal&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Included references to&#58; Cholestyramine&#44; colesevelam&#44; colestipol&#44; colextran&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Included references to oral hypoglycemic agents&#44; insulin&#44; and analogs&#46; ACE&#58; Angiotensin-converting enzyme&#59; NSAIDs&#58; non-steroidal anti-inflammatory drugs&#46;</p>"
            ]
            3 => array:3 [
              "identificador" => "tblfn0030"
              "etiqueta" => "d"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Treatments of interest has been searched in all EHRs in a pre-inclusion time-frame window &#40;&#8722;6&#44; &#43;1 months&#41; if not present at inclusion date&#46; The closest available entry to the inclusion date will be chosen&#46; Therefore&#44; the treatments depicted in the table does not necessarily occur concomitantly in time&#46; Time window&#58; Inclusion date &#91;&#8722;180d&#44; &#43;30d&#93;&#46;</p>"
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        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
            "identificador" => "at0025"
            "detalle" => "Table "
            "rol" => "short"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">All the variables included in this table were extracted from free-text&#44; and thus their frequencies are contingent upon the extent of their documentation in EHRs&#46;</p>"
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                  \t\t\t\t">3513 &#40;82&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Treatment switch&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">6534 &#40;14&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Treatment after switch&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Apixaban&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dabigatran&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">11 &#40;15&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5 &#40;1&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Edoxaban&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">14 &#40;3&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;3&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;3&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">846 &#40;12&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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Original article
Oral anticoagulant treatment in atrial fibrillation: the AFIRMA real-world study using natural language processing and machine learning
Tratamiento anticoagulante oral en la fibrilación auricular: AFIRMA, el estudio de vida real realizado mediante procesamiento de lenguaje natural y aprendizaje automático
J. Cosín-Salesa,
Corresponding author
jcosinsales@gmail.com

Corresponding author.
, M. Anguitab, C. Suárezc, C. Arias-Cabralesd, L. Martínez-Sanchezd, Savana Research Group d, D. Arumie, S. Fernández de Caboe
a Servicio de Cardiología, Hospital Arnau de Vilanova, Valencia, Spain
b Servicio de Cardiología, Hospital Universitario Reina Sofía, Córdoba, Spain
c Servicio de Medicina Interna, Hospital Universitario La Princesa, Madrid, Spain
d Savana Research S.L., Madrid, Spain
e Departamento Médico, Pfizer España, Madrid, Spain
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patients flow-chart&#46; Abbreviations&#58; EHRs&#44; electronic health records&#59; AF&#44; atrial fibrillation&#59; OAC&#44; oral anticoagulants&#59; VKAs&#44; vitamin K antagonist&#59; DOACs&#58; Direct oral anticoagulants&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Atrial fibrillation &#40;AF&#41; is the most common cardiac arrhythmia&#44; affecting 0&#46;51&#37; of people worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In Spain&#44; published studies reveal a prevalence of AF ranging from 1&#46;5&#37; to 4&#46;0&#37;&#44; with rates increasing with age&#8212;from 0&#46;04&#8722;0&#46;05&#37; among individuals under 45 years to 2&#46;3 &#37;&#8211;4&#46;6&#37; among those aged 60 years and above&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> AF is associated with high morbidity and markedly increases the risk of cerebrovascular events&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Therefore&#44; the prevention of systemic embolisms&#44; is the cornerstone of treatment in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Oral anticoagulation &#40;OAC&#41; with vitamin K antagonists &#40;VKA&#41;&#44; reduces stroke incidence and maintains an acceptable bleeding risk compared to aspirin in patients at moderate to high thromboembolic risk&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Nevertheless&#44; in clinical trials&#44; direct-acting OAC &#40;DOAC&#41; demonstrated superiorrisk&#8211;benefit and cost-effectiveness profiles compared to VKA for AF patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;8</span></a> Consequently&#44; clinical guidelines advocate them as first-line medications for the prevention of embolic events in AF patients&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> except in those with mechanical prosthetic valve or moderate to severe mitral stenosis&#44; where DOAC are contraindicated due to poorer outcomes compared to VKA&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> Additionally&#44; real-life observational studies mostly favor DOAC over VKA&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#8211;14</span></a> However&#44; most of these studies rely on databases based on claims or International Classification of Diseases &#40;ICD&#41; codes&#44; which may not accurately reflect the clinical reality of OAC treatment for AF&#46; In this regard&#44; studies in the field of cardiology show that unstructured data from electronic health records &#40;EHR&#41; free-text can enhance population characterization and prognostic algorithms performance&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#8211;17</span></a> The use of data extracted from EHRs through natural language processing &#40;NLP&#41; and machine learning &#40;ML&#41; techniques could provide more accurate insights into the epidemiological aspects and clinical characteristics of AF patients receiving OAC in Spain&#46; To our knowledge&#44; no studies have used these techniques to assess OAC use in AF patients&#46; The present study is framed within the larger AFIRMA &#40;<span class="elsevierStyleItalic">AF In Real practice on Management of oral Anticoagulation&#41;</span> Study&#44; aimed at identifying the demographic and clinical characteristics of patients with AF who were prescribed DOAC and VKA&#44; including comparing the rates of effectivity and strategy-related outcomes between them&#46; In this study&#44; we aimed to estimate the prevalence of in-hospital AF in Spain and to describe the clinical characteristics and anticoagulant treatment patterns among patients with AF receiving OAC&#46; This analysis was based on data from EHRs of patients attended in 15 participating centers&#44; representative of various regions in Spain&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study design</span><p id="par0015" class="elsevierStylePara elsevierViewall">This multicenter&#44; retrospective study utilized RWD from EHRs across 15 Spanish hospitals from the National Healthcare Network including 8 country&#39;s regions &#40;Supplementary Table S1&#41;&#46; Data was gathered from all departments of each site during the study period&#44; from January 2014 to December 2020&#46; The sample size was determined by the most stringent objective of the AFIRMA study&#44; which was not addressed in this study &#40;comparison of effectivity rates between DOAC and VKA&#41;&#46; Accepting an alpha risk of 0&#46;95&#44; the precision achieved with the participants we included to determine the proportion of patients taking VKA and the proportion of individuals switching from acenocoumarol to apixaban&#44; were &#60;0&#46;3 and &#60;1&#46;2&#44; indicating a high level of accuracy in our findings&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study population</span><p id="par0020" class="elsevierStylePara elsevierViewall">Among all patients who attended the participating hospitals during the study period&#44; the study population included AF patients on OAC treatment reported in their EHRs&#46; Patients below 18 years&#44; with rheumatic mitral valvular disease &#40;major cause of mitral stenosis&#41; venous thromboembolism&#44; or pregnancy were excluded&#46; Patients were stratified by OAC type&#44; into VKA and DOAC and a retrospective cross-sectional analysis was conducted at the index date &#40;first time a patient met all inclusion criteria during the study period&#41;&#46; Treatment-related variables were analyzed during the follow-up period&#44; ranging from index date to the latest EHR within the study period&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Data source and extraction</span><p id="par0025" class="elsevierStylePara elsevierViewall">Clinical data from EHRs were gathered from outpatient clinics&#44; hospitalization&#44; discharge summaries&#44; and other reports across all departments of each participating site&#46; Both unstructured and structured data &#40;when available&#41; were extracted and analyzed using the EHRead&#174; technology described elsewhere&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> which uses NLP and ML techniques to convert free text from EHRs into a study database&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a> After that&#44; a descriptive analysis of demographic and clinical characteristics was performed&#46; The used terminology encompassed codes&#44; synonyms&#44; and definitions from clinical documentation&#44; based on SNOMED CT&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Further details on EHRead<span class="elsevierStyleItalic">&#174;</span> technology are provided in the Supplemental methods&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">EHRead&#174; performance was externally validated as previously described&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Briefly&#44; expert physicians from each hospital annotated a random selection of EHRs containing study variables to set a comparison standard&#46; These external annotations were compared with the variables detected by EHRead&#174; in the same EHRs corpus&#46; Further details regarding EHR performance evaluation and specific metrics obtained are shown in the Supplemental methods and Supplementary Table S2&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Study variables</span><p id="par0035" class="elsevierStylePara elsevierViewall">The study variables were extracted and analyzed as part of a curation process that guaranteed the quality and integrity of the data&#46; Data on sociodemographic variables such as age and sex were collected&#46; In addition&#44; clinical variables&#44; including comorbidities&#44; laboratory data&#44; and medications were recorded&#46; Of note&#44; these concepts and their definitions were retrieved to the extent they were registered in the included EHRs&#46; To reconstruct patient history&#44; all information before index &#40;including information stemming from EHRs dated before study period start&#44; if available&#41; was analyzed&#46; For variables analyzed around discrete time points&#44; the closest value to the time point &#40;within reference time windows&#41; was taken&#46; Reference time windows accounted for the variability in healthcare management between patients&#44; specialists&#44; and hospitals&#44; maximizing data retrieval from EHRs&#46; Time window ranges for each variable or group of variables are detailed in table footnotes&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Data analyses</span><p id="par0040" class="elsevierStylePara elsevierViewall">Categorical and binary variables are summarized by frequencies&#44; numerical variables by median&#44; quartile 1&#44; quartile 3 &#40;Q1&#44; Q3&#41;&#44; and available value counts&#46; Annual AF prevalence was calculated dividing the yearly AF cases by the at-risk population in hospital areas&#44; determined using public health service data and basic health zone spatial databases&#46; The at-risk population was estimated from National Institute of Statistics databases&#44; merging 2011 census tract spatial data with provincial population distribution from 1970&#8722;2021&#46; Prevalence calculations extended only to 2018 due to incomplete data for 2019&#8211;2020 from some sites&#46; The number of patients with evaluable data is shown in the analysis for discrete and continuous variables&#46; Binary variables like comorbidities or symptoms were considered absent if not recorded&#46; Multi-level categorical&#44; lifestyle factors&#44; and numeric variables were not imputed&#46; Analysis was performed using &#34;R&#34; software &#40;version 4&#46;0&#46;2&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Ethical considerations and study approval</span><p id="par0045" class="elsevierStylePara elsevierViewall">The study obtained ethical approval from national and local Ethics committees&#44; adhering to regional regulations and any protocol changes underwent review&#46; It complied with local laws&#44; the latest Declaration of Helsinki&#44; and Good Pharmacoepidemiology Practices&#46; Data from anonymized EHRs preserved patient confidentiality&#44; avoiding the need for individual consent&#46; Being a retrospective study and using RWD&#44; collection and variable evaluation were conducted blindly&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Study population and prevalence of AF</span><p id="par0050" class="elsevierStylePara elsevierViewall">During the study period&#44; a total of 4&#44;664&#44;224 patients were attended to the participating hospitals&#46; Within this source population&#44; 138&#44;773&#44;332 EHRs underwent processing by EHRead&#174;&#46; Throughout the study period&#44; AF average prevalence was 2&#46;5&#37; rising from 1&#46;9&#37; in 2014 to 2&#46;9&#37; in 2018&#46;In terms of age&#44; the prevalence increased progressively starting at below 1&#37; in patients under 50 years&#44; increasing to 3&#46;5&#37; among those aged 60&#8211;69&#44; further to 8&#37; in the 70&#8211;79 age group&#44; and peaking at 15&#37; among individuals aged 80 years and above &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> and Supplementary Table S3&#41;&#46; In the descriptive analysis&#44; 57&#44;190 patients were included&#44; 46&#44;143 &#40;80&#46;7&#37;&#41; on VKA and 11&#44;047 &#40;19&#46;3 &#37;&#41; receiving DOAC &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Demographic&#44; clinical characteristics and treatments</span><p id="par0055" class="elsevierStylePara elsevierViewall">The median age of patients was 78 &#40;Q1&#44; Q3 69&#44; 84&#41; years&#44; 78 &#40;70&#44; 84&#41; years in the VKA&#44; and 76 &#40;67&#44; 83&#41; years in the DOAC group&#46; Males were 53&#37; overall&#44; 52&#37; in VKA group&#44; and 56&#37; in DOAC group &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Cardiovascular comorbidities were common among participants&#46; In the VKA group&#44; hypertension &#40;76&#46;3&#37;&#41;&#44; diabetes mellitus &#40;48&#46;0&#37;&#41;&#44; and heart failure &#40;42&#46;2&#37;&#41; were frequent&#46; Additionally&#44; 64&#46;0 &#37; had a CHA2DS2-VASc Score &#8805; 4&#46; International normalized ratio &#40;INR&#41; values were documented in the free text of EHRs for 51&#46;5&#37; of VKA patients&#44; with a median of 1&#46;94 &#40;1&#46;2&#44; 2&#46;8&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; In the DOAC group&#44; hypertension was observed in 72&#46;1&#37;&#44; diabetes mellitus in 41&#46;6&#37;&#44; and heart failure in 36&#46;4&#37;&#46; Up to 52&#46;0&#37; of these patients had a CHA2DS2-VASc Score &#8805; 4 &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">When examining concomitant treatments among all patients&#44; beta-blockers were the most prevalent medication at baseline &#40;51&#46;2&#37;&#41;&#44; followed by diuretics &#40;45&#46;9&#37;&#41;&#44; statins &#40;37&#46;4&#37;&#41;&#44; Angiotensin-converting enzyme &#40;ECA&#41; inhibitors &#40;27&#46;7&#37;&#41;&#44; angiotensin II antagonists &#40;26&#46;5&#37;&#41;&#44; and acetylsalicylic acid &#40;18&#46;8&#37;&#41;&#46; For the VKA group&#44; 47&#46;9&#37; of the patients were on diuretics&#44; and 38&#46;1&#37; on statins&#46; In the DOAC group&#44; 37&#46;5&#37; were on diuretics&#44; and 34&#46;5&#37; on statins &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Switch of OAC treatment</span><p id="par0065" class="elsevierStylePara elsevierViewall">In the study&#44; 8561 &#40;15&#46;0&#37;&#41; patients changed their OAC treatment&#46; Dabigatran &#40;19&#46;7&#37;&#41; and warfarin &#40;40&#46;2&#37;&#41; were the most switched treatments in the DOAC and VKA groups&#46; The most prevalent switch among VKA to DOAC was from acenocoumarol to apixaban &#40;35&#46;2&#37;&#41;&#46; On the other hand&#44; in the DOAC group&#44; the most common switch was from any drug to acenocoumarol&#44; with rates ranging between 58&#46;6&#37; and 70&#46;2&#37;&#46; The median duration of OAC use prior to switching varied across formulations&#44; being 478 &#40;Q1&#44; Q3 144&#46;0&#44; 976&#46;7&#41; days for acenocoumarol &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">The AFIRMA study represents the first attempt to apply NLP and ML for extracting and analyzing RWD from patients with AF on OAC treatment&#46; Thanks to this novel approach&#44; we were able to obtain detailed data from a large cohort &#40;<span class="elsevierStyleItalic">N</span>&#8239;&#61;&#8239;55&#44;824&#41; including patients from 15 hospitals from 8 health regions in Spain&#46; This provides a comprehensive overview of the epidemiology&#44; clinical characteristics&#44; and real-world OAC prescription trends in AF patients&#46; Findings indicate that these patients are predominantly elderly with multiple comorbidities&#44; mainly cardiovascular&#44; increasing stroke risk and medication use&#44; highlighting a fragile&#44; complex profile&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Our investigation unveiled an average AF prevalence of 2&#46;5&#37;&#44; which notably escalates to 8&#46;0&#37; among patients aged 70&#8211;79 years and further to 15&#37; among those aged 80 years or older&#46; This pattern aligns with previous studies conducted within the Spanish population&#46; For instance&#44; one study encompassing 8343 individuals reported an overall prevalence of 4&#37;&#44; with a rise to 9&#46;3&#37; among those aged 70&#8211;79 and 17&#46;7&#37; for those over 80&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Similarly&#44; another study involving 17&#44;291 participants indicated an overall prevalence of 1&#46;4&#37;&#44; which increased to 6&#46;3&#37; among individuals aged over 75 years&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Our study found VKAs prescribed in 80&#46;7&#37; of cases and DOACs in 19&#46;3&#37;&#46; Despite DOACs&#39; superior risk-benefit and cost-effectiveness&#44;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;8&#44;22</span></a> Spanish health ministry recommendations during the study period restricted their use to specific AF cases&#44; such as VKA hypersensitivity&#44; previous intracranial bleeding&#44; stroke with high hemorrhage risk&#44; suboptimal VKA response&#44; or INR control&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">23</span></a> This likely resulted in DOACs being relegated to a second-line role&#44; influenced by economic constraints&#46; Demographically and clinically&#44; VKA patients were older with more comorbidities and higher CHA2DS2-VASc score than DOAC patients&#44; aligning with both Spanish and international findings&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;24</span></a> Reflecting their comorbidities&#44; 61&#46;0&#37; of our AF cohort had very high CHA2DS2-VASc Scores &#40;&#8805;4&#41;&#44; indicating a substantial stroke risk&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">25</span></a> These patterns&#44; alongside the mentioned restrictions&#44; suggest that despite the clinical data supporting DOACs&#39; safety and efficacy in older comorbid patients&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">26</span></a> regulatory limitations might influence their real-world prescription&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Analytically&#44; INR levels in the VKA group were often at the lower end of recommended ranges&#46; Guidelines advise an INR of 2&#46;0&#8211;3&#46;0 for AF patients to balance thromboembolic prevention and bleeding risks&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Our findings are consistent with prior studies focused on the Spanish population&#44; where 40&#37;-60&#37; of patients had suboptimal INR ranges&#44;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">27&#8211;30</span></a> correlating with increased ischemic events risk&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">31</span></a> Given these results&#44; diligent INR monitoring and adjustment are crucial to optimize therapy and reduce risks for these patients&#46; Moreover&#44; AF patients frequently received medications primarily for cardiovascular conditions &#40;hypertension&#44; dyslipidemia&#41; and diabetes&#46; Also&#44; many take aspirin or nonsteroidal anti-inflammatory drugs &#40;NSAIDs&#41;&#44; which are associated with a higher bleeding risk when combined with OAC&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">32</span></a> The polypharmacy observed previously in AF patients in about 40&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">30</span></a> should be seen as a health status indicator&#44; requiring strategies to minimize inappropriate prescribing due to its association with increased cardiovascular mortality risk&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">33</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">We examined patients changing OAC treatments&#44; being the most common switch from a DOAC to acenocoumarol&#46; Among those transitioning from VKA to DOAC&#44; the predominant change was from acenocoumarol to apixaban&#46; Research focuses on VKA to DOAC transitions&#44; revealing risks and benefits&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">34</span></a> However&#44; RWD is scarce&#46; In this context&#44; a European study over 3 years showed that 5&#46;4&#37; of patients switched from VKA to DOAC&#44; and 8&#46;6&#37; presented the reversed shift&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">35</span></a> In our study&#44; the primary switch was from DOAC to acenocoumarol&#44; possibly due to previously mentioned DOAC prescription restrictions&#46; Switching from VKA to apixaban corresponds with a systematic review showing rising preference for apixaban&#44; increasing from 19&#46;8&#37; &#40;2011&#8211;2013&#41; to 45&#37; in 2015 in Europe&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">34</span></a> This preference is likely linked to apixaban&#39;s superior safety and security profile compared to VKA&#44; as demonstrated in the ARISTOTLE study&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">36</span></a> Additionally&#44; the ARISTOPHANES study&#44; based on RWD&#44; showed a comparative advantage over other DOACs like dabigatran and rivaroxaban&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> While many studies in the literature don&#39;t extensively report reasons for switching from DOAC to VKA&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">34</span></a> Hohnloser et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">37</span></a> analyzed a German claims database of over 50&#44;000 patients&#44; identifying age &#40;&#62;65 years&#41; and clinical events &#40;stroke&#44; myocardial infarction&#44; gastrointestinal bleeding&#44; and cardioversion&#41; as factors for switching from DOAC to VKA&#46; Conversely&#44; transitions from VKA to DOAC were due to therapy convenience&#44; poor anticoagulation profile&#44; bleeding&#44; patient decision&#44; and poor adherence&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">34</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">This multicenter study&#39;s primary strength is its use of innovative technology to create a comprehensive dataset of Spanish AF patients on OAC&#44; the largest to date&#46; Furthermore&#44; this technology allowed for extracting key information from unstructured free-text&#44; not just from structured ICD-coded data as in previous real-life studies&#46; However&#44; this study has limitations&#46; Its retrospective&#44; RWD-based nature led to some variables&#44; like specific switching reasons&#44; not being analyzable due to lack of well-documented causal relationship in EHR&#46; Additionally&#44; results are influenced by the characteristics of the Spanish healthcare system&#44; including restricted DOAC&#46; Finally&#44; the data&#44; sourced exclusively from hospitals&#44; may not fully represent the broader population of AF patients on OAC in ambulatory settings&#44; potentially limiting the extrapolation of our findings to the general population&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In summary&#44; the AFIRMA study&#44; pioneering in using NLP and ML to deeply describe AF patients undertaking OAC in Spain&#44; reveals significant AF prevalence&#44; with age as a key factor&#46; It shows a preference for VKA over DOAC&#44; highlights high comorbidity&#44; especially cardiovascular&#44; and notes polypharmacy&#44; especially in VKA patients&#46; We observed that most patients maintained their initial anticoagulant&#44; but among switchers&#44; DOAC to acenocoumarol was most common&#44; with VKA switchers favoring apixaban&#46; Our extensive patient sample and detailed analysis offer valuable insights into AF management and OAC optimization&#46; Nonetheless&#44; additional research is imperative to fully understand these medications&#39; real-world safety and efficacy&#44; especially considering the differences between patients on VKA and DOAC&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflicts of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">JCS&#44; MA &#38; CS were paid consultants to Pfizer in connection with the development of this study&#46; CAC &#38; LMS are employees of CRO&#46; DA &#38; SFC are employees of Pfizer&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Funding</span><p id="par0110" class="elsevierStylePara elsevierViewall">This study was sponsored by <span class="elsevierStyleGrantSponsor" id="gs0005">Bristol Myers Squibb&#47; Pfizer Alliance</span>&#46;</p></span></span>"
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              "titulo" => "Study population and prevalence of AF"
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    "fechaRecibido" => "2024-04-24"
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            0 => "Atrial fibrillation"
            1 => "Oral anticoagulation"
            2 => "Vitamin K antagonists"
            3 => "Direct oral anticoagulants"
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            5 => "Artificial intelligence"
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            0 => "AF"
            1 => "AI"
            2 => "DOAC"
            3 => "EHR"
            4 => "ICD"
            5 => "INR"
            6 => "ML"
            7 => "NLP"
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            0 => "Fibrilaci&#243;n auricular"
            1 => "Anticoagulaci&#243;n oral"
            2 => "Antagonistas de la vitamina K"
            3 => "Anticoagulantes orales directos"
            4 => "Evidencia en el mundo real"
            5 => "Inteligencia artificial"
            6 => "Procesamiento del lenguaje natural"
            7 => "Aprendizaje autom&#225;tico"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Oral anticoagulation &#40;OAC&#41; is key in atrial fibrillation &#40;AF&#41; thromboprophylaxis&#44; but Spain lacks substantial real-world evidence&#46; We aimed to analyze the prevalence&#44; clinical characteristics&#44; and treatment patterns among patients with AF undertaking OAC&#44; using natural language processing &#40;NLP&#41; and machine learning &#40;ML&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">This retrospective study included AF patients on OAC from 15 Spanish hospitals &#40;2014&#8211;2020&#41;&#46; Using EHRead&#174; &#40;including NLP and ML&#41;&#44; and SNOMED&#95;CT&#44; we extracted and analyzed patient demographics&#44; comorbidities&#44; and OAC treatment from electronic health records&#46; AF prevalence was estimated&#44; and a descriptive analysis was conducted&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Among 4&#44;664&#44;224 patients in our cohort&#44; AF prevalence ranged from 1&#46;9&#37; to 2&#46;9&#37;&#46; A total of 57&#44;190 patients on OAC therapy were included&#44; 80&#46;7&#37; receiving Vitamin K antagonists &#40;VKA&#41; and 19&#46;3&#37; Direct-acting OAC &#40;DOAC&#41;&#46; The median age was 78 and 76 years respectively&#44; with males constituting 53&#37; of the cohort&#46; Comorbidities like hypertension &#40;76&#46;3&#37;&#41;&#44; diabetes &#40;48&#46;0&#37;&#41;&#44; heart failure &#40;42&#46;2&#37;&#41;&#44; and renal disease &#40;18&#46;7&#37;&#41; were common&#44; and more frequent in VKA users&#46; Over 50&#37; had a high CHA2DS2-VASc score&#46; The most frequent treatment switch was from DOAC to acenocoumarol &#40;58&#46;6&#37; to 70&#46;2&#37;&#41;&#46; In switches from VKA to DOAC&#44; apixaban was the most chosen &#40;35&#46;2&#37;&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Utilizing NLP and ML to extract RWD&#44; we established the most comprehensive Spanish cohort of AF patients with OAC to date&#46; Analysis revealed a high AF prevalence&#44; patient complexity&#44; and a marked VKA preference over DOAC&#46; Importantly&#44; in VKA to DOAC transitions&#44; apixaban was the favored option&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">La anticoagulaci&#243;n oral &#40;ACO&#41; es clave en la tromboprofilaxis de la fibrilaci&#243;n auricular &#40;FA&#41;&#44; pero Espa&#241;a carece de evidencia relevante en el mundo real&#46; Nuestro objetivo fue analizar la prevalencia&#44; las caracter&#237;sticas cl&#237;nicas y los patrones de tratamiento en pacientes con FA en tratamiento con ACO&#44; utilizando el procesamiento del lenguaje natural &#40;PLN&#41; y el aprendizaje autom&#225;tico &#40;ML&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio retrospectivo en pacientes con FA en tratamiento con ACO de 15 hospitales espa&#241;oles &#40;2014&#8211;2020&#41;&#46; Utilizando EHRead&#174; &#40;incluyendo PNL y ML&#41;&#44; y SNOMED&#95;CT&#44; extrajimos y analizamos los datos demogr&#225;ficos de los pacientes&#44; las comorbilidades y el tratamiento con ACO de las historias cl&#237;nicas electr&#243;nicas&#46; Se estim&#243; la prevalencia de FA y se realiz&#243; un an&#225;lisis descriptivo&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">De los 4&#46;664&#46;224 pacientes de nuestra cohorte&#44; la prevalencia de FA oscil&#243; entre el 1&#44;9&#37; y el 2&#44;9&#37;&#46; Se incluyeron un total de 57&#46;190 pacientes en tratamiento con ACO&#44; de los cuales el 80&#44;7&#37; recib&#237;a antagonistas de la vitamina K &#40;AVK&#41; y el 19&#44;3&#37; ACO de acci&#243;n directa &#40;ACOD&#41;&#46; La mediana de edad fue de 78 y 76 a&#241;os&#44; respectivamente&#44; y los varones constituyeron el 53&#37; de la cohorte&#46; Las comorbilidades como hipertensi&#243;n arterial &#40;76&#44;3&#37;&#41;&#44; diabetes &#40;48&#44;0&#37;&#41;&#44; insuficiencia card&#237;aca &#40;42&#44;2&#37;&#41; y enfermedad renal &#40;18&#44;7&#37;&#41; fueron frecuentes y m&#225;s frecuentes en los usuarios de AVK&#46; M&#225;s del 50&#37; ten&#237;a una puntuaci&#243;n alta de CHA2DS2-VASc&#46; El cambio de tratamiento m&#225;s frecuente fue de ACOD a acenocumarol &#40;58&#44;6&#37; a 70&#44;2&#37;&#41;&#46; En los cambios de AVK a ACOD&#44; apixab&#225;n fue el m&#225;s elegido &#40;35&#44;2&#37;&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Utilizando PNL y ML para extraer la RWD&#44; establecimos la cohorte espa&#241;ola m&#225;s completa de pacientes con FA tratados con ACO hasta la fecha&#46; El an&#225;lisis revel&#243; una alta prevalencia de FA&#44; complejidad de los pacientes y una marcada preferencia por AVK sobre el ACOD&#46; Es importante destacar que&#44; en las transiciones de AVK a ACOD&#44; apixab&#225;n fue la opci&#243;n preferida&#46;</p></span>"
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            "apendice" => "<p id="par0130" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patients flow-chart&#46; Abbreviations&#58; EHRs&#44; electronic health records&#59; AF&#44; atrial fibrillation&#59; OAC&#44; oral anticoagulants&#59; VKAs&#44; vitamin K antagonist&#59; DOACs&#58; Direct oral anticoagulants&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estimate prevalence of AF by age&#46; Of note&#44; the yearly incidence was estimated until 2018 to include patient follow-up data from all participating sites&#46; The at-risk population considered for calculating AF prevalence each year was as follows&#58; 2014&#58; 3&#44;194&#44;788&#59; 2015&#58; 3&#44;208&#44;773&#59; 2016&#58; 4&#44;513&#44;867&#59; 2017&#58; 5&#44;202&#44;572&#59; and 2018&#58; 3&#44;767&#44;266&#46;</p>"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">All the variables included in this table were extracted from free-text&#44; and thus their frequencies are contingent upon the extent of their documentation in EHRs&#46; Abbreviations&#58; VKA&#44; vitamin K antagonist&#44; DOAC&#44; direct-acting oral anticoagulants&#44; IQR&#44; interquartile range&#59; INR&#58; International Normalized Ratio&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Overall &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;57&#44;190&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">VKA &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;46&#44;143&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">DOAC &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;11&#44;047&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&#44; years&#44; median&#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78 &#40;69&#44; 84&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78 &#40;70&#44; 84&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76 &#40;67&#44; 83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male sex&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#44;110&#40;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#44;908 &#40;52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6202 &#40;56&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Comorbidities&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#44;655 &#40;76&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#44;687 &#40;77&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7968 &#40;72&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Heart failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#44;150 &#40;42&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#44;124 &#40;43&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4026 &#40;36&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#44;452 &#40;48&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#44;857 &#40;49&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4595 &#40;41&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Renal disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;669 &#40;18&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9022 &#40;19&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1647 &#40;14&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Coronary disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5911 &#40;10&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4910 &#40;10&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1001 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pulmonary disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5909 &#40;10&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4974 &#40;10&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">935 &#40;8&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Transient ischemic attack&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3282 &#40;5&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2642 &#40;5&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">640 &#40;5&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Myocardial infarction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2302 &#40;4&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1891 &#40;4&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">411 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hemodialysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">828 &#40;1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">782 &#40;1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46 &#40;0&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CHA2DS2-VASc Score<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1124 &#40;2&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">655 &#40;1&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">469 &#40;4&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3075 &#40;5&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2185 &#40;5&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Overall &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;57&#44;190&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Beta blockers&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4138 &#40;37&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ACE inhibitors&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">15&#44;813 &#40;27&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13&#44;311 &#40;28&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2502 &#40;22&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Angiotensin II antagonists&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">12&#44;223 &#40;26&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2966 &#40;26&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antidiabetic agents&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">24&#44;983 &#40;43&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#44;894 &#40;43&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4089 &#40;37&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Lipid-lowering drugs&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Statins&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">21&#44;397 &#40;37&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#44;591 &#40;38&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3806 &#40;34&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Fibrates&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1551 &#40;2&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1353 &#40;2&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">198 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">107 &#40;0&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ezetimiba&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">845 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Clopidogrel&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Others<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">677 &#40;1&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">NSAIDs&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6037 &#40;10&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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            1 => array:3 [
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            2 => array:3 [
              "identificador" => "tblfn0025"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Included references to oral hypoglycemic agents&#44; insulin&#44; and analogs&#46; ACE&#58; Angiotensin-converting enzyme&#59; NSAIDs&#58; non-steroidal anti-inflammatory drugs&#46;</p>"
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            3 => array:3 [
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">All the variables included in this table were extracted from free-text&#44; and thus their frequencies are contingent upon the extent of their documentation in EHRs&#46;</p>"
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">No switch in treatment&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3080 &#40;89&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2205 &#40;80&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">530 &#40;88&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3513 &#40;82&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">38&#44;843 &#40;85&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">458 &#40;59&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Treatment switch&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">366 &#40;10&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">540 &#40;19&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70 &#40;11&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">743 &#40;17&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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