Anticoagulation control in hospitalized patients with nonvalvular atrial fibrillation undergoing long-term oral anticoagulant therapy

Batalla Insenser, B.; Pertierra Uriel, U.; Sánchez Biosca, A.; Sobrino Martínez, J.

doi:10.1016/j.rceng.2018.03.003

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Batalla Insenser, U. Pertierra Uriel, A. Sánchez Biosca, J. Sobrino Martínez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "B." "apellidos" => "Batalla Insenser" ] 1 => array:2 [ "nombre" => "U." "apellidos" => "Pertierra Uriel" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Sánchez Biosca" ] 3 => array:4 [ "nombre" => "J." "apellidos" => "Sobrino Martínez" "email" => array:1 [ 0 => "jsobrino@hes.scs.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Medicina Interna, Fundació Hospital de l’Esperit Sant, Santa Coloma de Gramenet (Barcelona), Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Control de la anticoagulación en pacientes hospitalizados con fibrilación auricular no valvular en tratamiento crónico con anticoagulantes orales" ] ] "textoCompleto" => "Atrial fibrillation (AF) is the most common arrhythmia in our setting, especially in older patients or those with associated comorbidity,<a class="elsevierStyleCrossRef" href="#bib0065">1</a> who represent the profile of patients treated in internal medicine departments. In a recent Spanish study, up to 17% of hospitalized patients in the medical area presented AF.<a class="elsevierStyleCrossRef" href="#bib0070">2</a>In the absence of contraindication, anticoagulation is indicated for most elderly patients with nonvalvular AF (NVAF) to reduce the risk of thromboembolic complications.<a class="elsevierStyleCrossRef" href="#bib0075">3</a> Although the prescription of direct oral anticoagulants is gaining ground, the “classical” vitamin K antagonists (VKAs) are still the most widely used drugs for patients with NVAF.<a class="elsevierStyleCrossRef" href="#bib0080">4</a> VKAs are highly effective but have 2significant limitations that can reduce their anticoagulant effect: the narrow therapeutic window and the need for periodic coagulation checks that entail frequent dosage adjustments.<a class="elsevierStyleCrossRef" href="#bib0075">3</a> For the anticoagulation to be effective and safe, we need to maintain an adequate time in therapeutic range (TTR).<a class="elsevierStyleCrossRef" href="#bib0085">5</a> However, data from Bertomeu-González et al. confirm that anticoagulation control in patients treated in outpatient clinics in Spain is insufficient<a class="elsevierStyleCrossRef" href="#bib0090">6</a> and that there is little information on the management of anticoagulation and its clinical consequences in patients hospitalized with AF.<a class="elsevierStyleCrossRef" href="#bib0095">7</a> We therefore conducted an observational study to assess the degree of anticoagulation control in hospitalized patients with NVAF treated with VKAs, as well as the factors and events associated with this control.We retrospectively reviewed the medical records of all patients with a previous diagnosis of NVAF hospitalized in our hospital's Department of Internal Medicine during 2015. The study included 231 patients, most of whom were octogenarians (mean age, 81.1±8.1 years), 53% of whom were men. The thromboembolic risk was high, given that 96.1% of the patients had a CHA2DS2-VASc level ≥2 (mean, 4.7±1.5), with a mean score on the HAS-BLED scale of 2.0±0.9.More than half of the patients had associated comorbidities (Charlson comorbidity index≥3 in 58.2% of the patients), with a high prevalence of arterial hypertension (83.1%). Infectious processes were the main cause of hospitalization (51.1% of cases), and the mean hospital stay was 8.59±4.34 days (range, 3–29 days).Most of the patients (96.1%) followed some type of antithrombotic therapy before the hospitalization: oral anticoagulants (77.1%: 67.5% with VKAs and 9.6% with direct oral anticoagulants), antiplatelets (17.7%) or low-molecular-weight heparins (1.3%). During the hospitalization, 148 patients (64.1%) continued with VKAs, although only 18 (12.1% of all those treated with VKAs) remained in the therapeutic range, significantly worsening the anticoagulation control in the patients with VKAs (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The multivariate analysis using logistic regression showed that the only variable associated with poor anticoagulation control was an inadequate TTR before the hospitalization (relative risk, 2.5; 95% confidence interval 1.33–4.68; p=.009).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>In the patients treated with VKAs and poor coagulation control, the hospitalization was longer (9.09±4.91 vs. 7.03±1.88 days; p=.029), and the number of clinical events during the hospitalization and follow-up was greater than among the patients who remained in the therapeutic range, although the difference did not achieve statistical significance during the hospitalization (p=.213), at 1 month (p=.922) or at 3 months of follow-up (p=.694).After the hospital discharge, 150 patients (64.9%) continued the VKA therapy despite poorer anticoagulation control during their hospitalization, and 60 (26%) did not undergo anticoagulant therapy, which represents a 4.3% increase in the number of patients without anticoagulant therapy compared with baseline. This increase is due to a greater number of patients treated with antiplatelets (19.5%) and especially patients without antithrombotic therapy (6.5%). In all medical records of the patients without anticoagulant therapy, the reason for the hospitalization was mentioned, which was mainly frequent falls.The patients’ clinical profile (elderly, high thromboembolic risk and numerous comorbidities) was similar to that of other studies<a class="elsevierStyleCrossRefs" href="#bib0070">2,8</a> and showed the considerable complexity of patients with AF hospitalized in internal medicine. Despite the high thromboembolic risk, the results showed that a non-negligible portion of patients were not anticoagulated. More than 20% of the patients were not treated with anticoagulant therapy before the hospitalization, and more than 25% did not receive it when discharged.In the elderly population, the use of anticoagulant therapy decreases, and the use of antiplatelets increases.<a class="elsevierStyleCrossRef" href="#bib0075">3</a> However, it has been shown that antiplatelet therapy is highly ineffective for this type of patient and has a hemorrhage risk similar to that of anticoagulation<a class="elsevierStyleCrossRef" href="#bib0105">9</a> and should therefore be avoided. Various causes have been indicated to explain the underutilization of anticoagulant therapy in elderly patients, such as advanced age, cognitive impairment and the presence of other comorbidities, such as renal failure.<a class="elsevierStyleCrossRefs" href="#bib0095">7,10</a> However, none of these causes in isolation is a contraindication for this therapy.<a class="elsevierStyleCrossRef" href="#bib0075">3</a>The percentage of patients with good anticoagulation control in our study (12% during the hospitalization) was lower than that observed in other studies (45–55%). This difference could be attributed to the older age and number of comorbidities of the study sample. As in the PAULA study,<a class="elsevierStyleCrossRef" href="#bib0115">11</a> the main factor associated with poor anticoagulation control was a labile international normalized ratio, with a low TTR before the hospitalization. The control worsened during the hospitalization, and, as in other studies,<a class="elsevierStyleCrossRef" href="#bib0120">12</a> this change was associated with a longer hospital stay and more clinical events. Direct oral anticoagulants could be a reasonable alternative to VKA for elderly patients with poor anticoagulation control.<a class="elsevierStyleCrossRef" href="#bib0075">3</a> However, the use of these oral anticoagulants in Spain is relatively low." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Insenser BB, Uriel UP, Biosca AS, Martínez JS. Control de la anticoagulación en pacientes hospitalizados con fibrilación auricular no valvular en tratamiento crónico con anticoagulantes orales. Rev Clin Esp. 2018;218:267–269." ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Abbreviations: NVAF, nonvalvular atrial fibrillation; VKA, vitamin K antagonists." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Before hospitalization \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">During hospitalization \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">Time in therapeutic range (%)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a></td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Direct method \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24.92±33.58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18.54±29.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.041 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rosendaal method \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26.88±35.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22.43±31.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.116 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">Patients with adequate anticoagulation control</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Direct method<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rosendaal method<a class="elsevierStyleCrossRef" href="#tblfn0015">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19.2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1757306.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "The time in therapeutic range (TTR) is expressed as the percentage of time throughout the hospitalization in which the patients had an international normalized ratio (INR) between 2 and 3. 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of the patients&#41;&#44; with a high prevalence of arterial hypertension &#40;83&#46;1&#37;&#41;&#46; Infectious processes were the main cause of hospitalization &#40;51&#46;1&#37; of cases&#41;&#44; and the mean hospital stay was 8&#46;59<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;34 days &#40;range&#44; 3&#8211;29 days&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Most of the patients &#40;96&#46;1&#37;&#41; followed some type of antithrombotic therapy before the hospitalization&#58; oral anticoagulants &#40;77&#46;1&#37;&#58; 67&#46;5&#37; with VKAs and 9&#46;6&#37; with direct oral anticoagulants&#41;&#44; antiplatelets &#40;17&#46;7&#37;&#41; or low-molecular-weight heparins &#40;1&#46;3&#37;&#41;&#46; During the hospitalization&#44; 148 patients &#40;64&#46;1&#37;&#41; continued with VKAs&#44; although only 18 &#40;12&#46;1&#37; of all those treated with VKAs&#41; remained in the therapeutic range&#44; significantly worsening the anticoagulation control in the patients with VKAs &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The multivariate analysis using logistic regression showed that the only variable associated with poor anticoagulation control was an inadequate TTR before the hospitalization &#40;relative risk&#44; 2&#46;5&#59; 95&#37; confidence interval 1&#46;33&#8211;4&#46;68&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;009&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In the patients treated with VKAs and poor coagulation control&#44; the hospitalization was longer &#40;9&#46;09<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;91 vs&#46; 7&#46;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;88 days&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;029&#41;&#44; and the number of clinical events during the hospitalization and follow-up was greater than among the patients who remained in the therapeutic range&#44; although the difference did not achieve statistical significance during the hospitalization &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;213&#41;&#44; at 1 month &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;922&#41; or at 3 months of follow-up &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;694&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">After the hospital discharge&#44; 150 patients &#40;64&#46;9&#37;&#41; continued the VKA therapy despite poorer anticoagulation control during their hospitalization&#44; and 60 &#40;26&#37;&#41; did not undergo anticoagulant therapy&#44; which represents a 4&#46;3&#37; increase in the number of patients without anticoagulant therapy compared with baseline&#46; This increase is due to a greater number of patients treated with antiplatelets &#40;19&#46;5&#37;&#41; and especially patients without antithrombotic therapy &#40;6&#46;5&#37;&#41;&#46; In all medical records of the patients without anticoagulant therapy&#44; the reason for the hospitalization was mentioned&#44; which was mainly frequent falls&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The patients&#8217; clinical profile &#40;elderly&#44; high thromboembolic risk and numerous comorbidities&#41; was similar to that of other studies<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">2&#44;8</span></a> and showed the considerable complexity of patients with AF hospitalized in internal medicine&#46; Despite the high thromboembolic risk&#44; the results showed that a non-negligible portion of patients were not anticoagulated&#46; More than 20&#37; of the patients were not treated with anticoagulant therapy before the hospitalization&#44; and more than 25&#37; did not receive it when discharged&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In the elderly population&#44; the use of anticoagulant therapy decreases&#44; and the use of antiplatelets increases&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> However&#44; it has been shown that antiplatelet therapy is highly ineffective for this type of patient and has a hemorrhage risk similar to that of anticoagulation<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a> and should therefore be avoided&#46; Various causes have been indicated to explain the underutilization of anticoagulant therapy in elderly patients&#44; such as advanced age&#44; cognitive impairment and the presence of other comorbidities&#44; such as renal failure&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">7&#44;10</span></a> However&#44; none of these causes in isolation is a contraindication for this therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The percentage of patients with good anticoagulation control in our study &#40;12&#37; during the hospitalization&#41; was lower than that observed in other studies &#40;45&#8211;55&#37;&#41;&#46; This difference could be attributed to the older age and number of comorbidities of the study sample&#46; As in the PAULA study&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">11</span></a> the main factor associated with poor anticoagulation control was a labile international normalized ratio&#44; with a low TTR before the hospitalization&#46; The control worsened during the hospitalization&#44; and&#44; as in other studies&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">12</span></a> this change was associated with a longer hospital stay and more clinical events&#46; Direct oral anticoagulants could be a reasonable alternative to VKA for elderly patients with poor anticoagulation control&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> However&#44; the use of these oral anticoagulants in Spain is relatively low&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; Insenser BB&#44; Uriel UP&#44; Biosca AS&#44; Mart&#237;nez JS&#46; Control de la anticoagulaci&#243;n en pacientes hospitalizados con fibrilaci&#243;n auricular no valvular en tratamiento cr&#243;nico con anticoagulantes orales&#46; Rev Clin Esp&#46; 2018&#59;218&#58;267&#8211;269&#46;</p>"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; NVAF&#44; nonvalvular atrial fibrillation&#59; VKA&#44; vitamin K antagonists&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Before hospitalization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">During hospitalization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Time in therapeutic range &#40;&#37;&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;Mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;Mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Direct method&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#46;92<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>33&#46;58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#46;54<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>29&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;041&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rosendaal method&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&#46;88<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>31&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;116&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Patients with adequate anticoagulation control</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Direct method<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rosendaal method<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">The time in therapeutic range &#40;TTR&#41; is expressed as the percentage of time throughout the hospitalization in which the patients had an international normalized ratio &#40;INR&#41; between 2 and 3&#46; The results are shown as means<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviations of this percentage&#44; before and during the hospitalization of patients treated with VKAs&#46;</p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">TTR<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>60&#37;&#46;</p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">TTR<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>65&#37;&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Time in therapeutic range and appropriate anticoagulation control before and during the hospitalization of patients with nonvalvular atrial fibrillation treated with vitamin K antagonists&#46;</p>"
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