For and against
Extended anticoagulation in venous thromboembolism disease. In favor
Anticoagulación extendida en la enfermedad tromboembólica venosa. A favor
M.C. Fernández
Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain
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In favor of short-term courses" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "365" "paginaFinal" => "369" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Duración del tratamiento anticoagulante. A favor de plazos cortos" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1837 "Ancho" => 2344 "Tamanyo" => 125486 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Adverse events during the follow-up and patients with treated venous thromboembolism. Incidence rate of death by pulmonary embolism (black lines) and hemorrhage (red lines) in 53,222 patients diagnosed with pulmonary embolism and deep vein thrombosis, after the third month following the diagnosis. The deaths by hemorrhage always exceeded those due to pulmonary embolism. For a more adjusted comparison, we must subtract 0.14% (0.06–0.26%) of annual deaths that occur if these patients were not anticoagulated from the number of deaths by hemorrhage. <span class="elsevierStyleItalic">Abbreviations</span>: PE: pulmonary embolism; DVT: deep vein thrombosis. <span class="elsevierStyleItalic">Source</span>: RIETE registry (unpublished data) and Castellucci et al.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">21</span></a></p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.A. Nieto Rodríguez, J.C. Ramírez Luna" "autores" => array:2 [ 0 => array:2 [ "nombre" => "J.A." "apellidos" => "Nieto Rodríguez" ] 1 => array:2 [ "nombre" => "J.C." "apellidos" => "Ramírez Luna" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0014256517300759" "doi" => "10.1016/j.rce.2017.02.012" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256517300759?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887417300401?idApp=WRCEE" "url" => "/22548874/0000021700000006/v1_201707280038/S2254887417300401/v1_201707280038/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S225488741730067X" "issn" => "22548874" "doi" => "10.1016/j.rceng.2017.05.001" "estado" => "S300" "fechaPublicacion" => "2017-08-01" "aid" => "1390" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Rev Clin Esp. 2017;217:351-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 4 "formatos" => array:2 [ "HTML" => 2 "PDF" => 2 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Symposium. Polypathology</span>" "titulo" => "Care models for polypathological patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "351" "paginaFinal" => "358" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Modelos de atención al paciente pluripatológico" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "<span class="elsevierStyleItalic">Source</span>: Innovative care for chronic conditions: organization and delivery of high-quality care of noncommunicable chronic diseases in the Americas." "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1120 "Ancho" => 2498 "Tamanyo" => 162675 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The care model for patients with chronic diseases.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Fernández Moyano, J.M. Machín Lázaro, M.D. Martín Escalante, M.B. Aller Hernandez, I. Vallejo Maroto" "autores" => array:5 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Fernández Moyano" ] 1 => array:2 [ "nombre" => "J.M." "apellidos" => "Machín Lázaro" ] 2 => array:2 [ "nombre" => "M.D." "apellidos" => "Martín Escalante" ] 3 => array:2 [ "nombre" => "M.B." "apellidos" => "Aller Hernandez" ] 4 => array:2 [ "nombre" => "I." "apellidos" => "Vallejo Maroto" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0014256517301017" "doi" => "10.1016/j.rce.2017.03.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256517301017?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S225488741730067X?idApp=WRCEE" "url" => "/22548874/0000021700000006/v1_201707280038/S225488741730067X/v1_201707280038/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">For and against</span>" "titulo" => "Extended anticoagulation in venous thromboembolism disease. In favor" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "359" "paginaFinal" => "364" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "M.C. Fernández" "autores" => array:1 [ 0 => array:3 [ "nombre" => "M.C." "apellidos" => "Fernández" "email" => array:1 [ 0 => "Capitanmfcapitan@salud.madrid.org" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Anticoagulación extendida en la enfermedad tromboembólica venosa. A favor" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Venous thromboembolism (VTE) is a severe disease that, despite diagnostic and therapeutic advances, has high mortality (13%) and causes significant sequela such as pulmonary hypertension (3% annually) and postthrombotic syndrome (PTS) (30% in 8 years).<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">1,2</span></a> VTE can be considered a chronic disease because after an initial episode, the annual risk of recurrence is 2–3.8%, reaching 30–50% in 10 years, with an associated mortality of 3–18%.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">3–5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Clinical practice guidelines<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">6,7</span></a> recommend anticoagulant therapy of limited duration for most patients with VTE, but the high risk of recurrence necessitates prolonging the therapy in many cases.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">8</span></a> Although prolonged anticoagulation is effective, the risk of recurrence remains when withdrawn, and the optimal treatment duration is not known.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">9</span></a> Therefore, the most difficult decision in VTE is not the anticoagulation nor what treatment to employ but rather when to discontinue the anticoagulant therapy after a limited treatment time.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The American College of Chest Physicians (ACCP)<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">6</span></a> guidelines suggest 3 months for patients with “provoked” VTE as the most appropriate treatment duration, with various evidence-based grades of recommendation. Furthermore, the guidelines recommend extending the anticoagulation, without a scheduled completion date (“extended anticoagulation”), for those patients with recurrent idiopathic VTE or VTE associated with cancer.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The fundamental uncertainty in extending anticoagulation arises with patients who have experienced an initial episode of unprovoked VTE, especially in those without a high risk of bleeding. There is no clinical prediction rule that classifies these patients. This difficult decision is based on a careful assessment of the risks and benefits of anticoagulation; the benefit in preventing a recurrence and its consequences and the risk of hemorrhage, especially the dreaded intracranial hemorrhage.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The decision to maintain anticoagulation should be based mainly on the risk of recurrence, because the risk of hemorrhage is secondary, difficult to predict and should be assumed when the risk of recurrence is high. In any case, clear and understandable information needs to be provided to the patient, and their opinion must be taken into consideration before making the definitive decision.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Risk of recurrence and hemorrhage</span><p id="par0030" class="elsevierStylePara elsevierViewall">The risk of recurrence remains throughout the patient's life. Although the risk is greater in the case of idiopathic VTE, the risk is also present when there are risk factors (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). To facilitate the therapeutic decision, we must find factors that can help stratify the risk of recurrence, such as the patient's sex and D-dimer concentration measured 1 month after anticoagulation is discontinued. Men have a risk of recurrence 1.75-fold greater than that of women, and patients with high D-dimer levels have twice the risk of those who have normal levels.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">9–11</span></a> Other factors have also been considered, such as age (<50 years), persistence of venous thrombosis (>40% of the lumen obstructed, relative risk [RR] 1.5),<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">12</span></a> thrombophilia (RR, 1.5; antiphospholipid syndrome RR, 2)<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">13</span></a> and PTS. Lastly, it is important to consider the VTE's initial clinical expression. Patients with proximal deep vein thrombosis (DVT) have a recurrence risk 5-fold higher than those with distal DVT. Patients with pulmonary embolism (PE) have a 3-fold higher risk that the recurrence will manifest as a new episode of PE, with the consequent increase in mortality.<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">14,15</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Many of these factors have been collected into recurrence prediction scales.<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">11–17</span></a> A recurrence risk <5% a year or 15% at 5 years is considered acceptable and justifies discontinuing the anticoagulation after 3 months of treatment. However, the lack of validation for these factors results in a lack of firm recommendations on their use for deciding the anticoagulation during after an initial idiopathic VTE.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">18</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">There are also scales for estimating the risk of hemorrhage, inherent in anticoagulant therapy, based on the presence of various factors. Once again, the usefulness of these scales for assessing the extension of anticoagulation is limited by the fact that the scales are based on studies performed with patients who are anticoagulated for other causes or with patients with VTE during a treatment with a preset duration.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Risk–benefit balance of extending anticoagulation</span><p id="par0045" class="elsevierStylePara elsevierViewall">The most severe consequence of a recurrence or hemorrhage is the patient's death. The overall mortality rate for recurrent VTE is 3.6% (1.9–5.7%).<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">3–5</span></a> The mortality rate for hemorrhage varies over time. According to a meta-analysis, the rate of major hemorrhage in the first 3 months of anticoagulation is 2.06% (2.04–2.08%), and the rate of fatal hemorrhage is 0.37% (0.36–0.38%),<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">19</span></a> which is similar to that observed in patients of the Computerized Registry of Patients with Thromboembolism (RIETE), with readings of 2.2% and 0.56%, respectively.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">20</span></a> After 3 months, these rates are 2.74% and 0.63%, respectively.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">15</span></a> Much of these data come from retrospective studies and clinical trials performed with selected patients or those who were treated with anticoagulation for a limited time. The studies and trials therefore underestimate the actual incidence rate of recurrence, and their validity for making decisions on treatment prolongation is questionable. It is important to consider that nonfatal recurrences are also important, because they can cause a PTS and chronic and progressive impairment of the patient's cardiopulmonary situation, with the consequent emotional, social and financial costs.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Studies performed<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">5,21</span></a> to compare treatment durations in patients with a first episode of VTE who had completed 6 months of treatment have shown that vitamin K antagonists (VKAs), with a therapeutic objective according to an international normalized ratio (INR) of 2.5 (between 2 and 3), were highly effective in preventing new thrombotic events. However, after discontinuing the anticoagulation, the recurrence risk was the same for those treated for 6 or 24 months.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The studies<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">10,22,23</span></a> that compared anticoagulation prolongation with VKA for more than 3 months with treatment discontinuation for patients with idiopathic VTE have shown that long-term anticoagulation reduces recurrences in 90% of these patients. As with other studies, recurrence rates were high in patients without extended treatment, estimated at 10% in the first year, 30% at 5 years and up to a 50% at 10 years.<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">2,22–25</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The risk of major hemorrhage increased during extended anticoagulation (1–2% at 1 year, RR, 1.8; 95% confidence interval [95% CI] 0.7–4.5),<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">23</span></a> with only half of the hemorrhages attributable to treatment.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">23</span></a> The cumulative frequency of the composite variable “recurrent VTE and major hemorrhage” was much lower in the patients who remained anticoagulated,<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">11,23–26</span></a> and the benefit was greater the longer the follow-up.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">23</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Approximately 10% of major hemorrhages during extended treatment are fatal,<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">19</span></a> while mortality due to recurrence is approximately 5% for DVT and 15–18% for PE.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">5,25,27</span></a> Although the mortality due to hemorrhages can be greater than that due to recurrence, the large number of recurrences outweighs the consequences of the increase in hemorrhages if the anticoagulation is extended.</p><p id="par0070" class="elsevierStylePara elsevierViewall">We should also consider that the rates of hemorrhage and recurrence in patients with VKA are related to the degree of anticoagulation control, with lower rates for patients with a time in therapeutic range (TTR) ≥70% (RR, 0.50; 95% CI 0.39–0.63) compared with those with TTR <30%.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">28</span></a> The current challenge is therefore focused on choosing the safest and most effective drug for extending the anticoagulation.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Reducing recurrent venous thromboembolism with extended anticoagulation: efficacy</span><p id="par0075" class="elsevierStylePara elsevierViewall">Extended anticoagulation with VKA reduces recurrent VTE by 90% (RR, 0.12; 95% CI 0.05–0.25), with half of recurrences occurring in patients who prematurely discontinued the treatment.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">29</span></a> This treatment also reduces the combined result of “recurrent VTE, major hemorrhage and death” by 50% when compared with the absence of anticoagulation.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">23</span></a> These results support the efficacy of prolonged treatment.<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">23,29</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Similar reductions in recurrence (>80–92%) have been demonstrated with extended anticoagulation using direct oral anticoagulants (DOAs) versus placebo (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">30–32</span></a> Low-molecular-weight heparins (LMWHs) are also highly effective,<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">33</span></a> especially in patients with cancer, for whom the use of LMWHs is preferable to VKAs.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">34</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Reducing major hemorrhages with extended anticoagulation: safety</span><p id="par0085" class="elsevierStylePara elsevierViewall">Anticoagulation with VKAs is associated with an increased risk of major hemorrhage (RR, 2.63; 95% CI 1.02–6.78).<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">35</span></a> DOAs have been compared with VKAs for the extended treatment of VTE<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">30–36</span></a> and have been shown to be equally effective but safer, because DOAs are associated with fewer major hemorrhages, with half the number of intracranial hemorrhages and a smaller reduction in extracranial hemorrhages. Therefore, although the type of anticoagulant therapy should not be decisive in selecting the treatment duration, DOAs are a safer alternative for prolonging the anticoagulation (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Other non-anticoagulant drugs have been researched for preventing VTE recurrence, such as acetylsalicylic acid (ASA)<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">37</span></a> and sulodexide.<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">38</span></a> The efficacy of these 2 drugs has been lower, with a reduction in recurrence of 30% and 50%, respectively. For ASA, the hemorrhage rates are similar to those of some DOAs.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">32</span></a> Therefore, these drugs are not an alternative for patients without a contraindication for anticoagulation.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Extended anticoagulation? In favor</span><p id="par0095" class="elsevierStylePara elsevierViewall">The most difficult decision in VTE is not the anticoagulation nor what treatment to employ but rather when to discontinue the anticoagulant therapy after a limited treatment time. Before deciding to end or extend the anticoagulation for a patient with VTE, we should remember that…<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall">The risk of thrombosis recurrence remains throughout the patient's life. Although the risk is greater in the case of idiopathic VTE, the risk is also present with “provoked” VTE.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall">The mortality rate for VTE recurrence is 3–18%. Nonfatal recurrences are also relevant (PTS, heart failure and respiratory failure).</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall">The risk of hemorrhage (the main obstacle for maintaining anticoagulation) is secondary, because it is difficult to predict and must be assumed when the recurrence risk is high.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0115" class="elsevierStylePara elsevierViewall">The reduction in recurrent VTE with VKAs (90%)<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">29</span></a> supports the efficacy of prolonged anticoagulant therapy.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0120" class="elsevierStylePara elsevierViewall">Similar reductions in recurrence (>80–92%) have been observed with DOAs.<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">30–32</span></a></p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0125" class="elsevierStylePara elsevierViewall">For patients undergoing treatment with VKAs, the recurrence and hemorrhage risk is related to poor anticoagulation control.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0130" class="elsevierStylePara elsevierViewall">In extended treatment, DOAs have been shown to be as effective as VKAs but are safer (fewer major hemorrhages and intracranial hemorrhages).</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0135" class="elsevierStylePara elsevierViewall">DOAs do not need dose adjustments and have fewer disadvantages compared with VKA anticoagulation (e.g., laboratory checks and drug and food interactions).</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0140" class="elsevierStylePara elsevierViewall">There are no alternative drugs for anticoagulant therapy as effective in preventing recurrence that are exempt from hemorrhagic risk.</p></li></ul></p><p id="par0145" class="elsevierStylePara elsevierViewall">Lastly, it is important to remember that the choice of extending the anticoagulation should always be individualized according to the patient's characteristics. The decision to proceed with “extended anticoagulation” is not synonymous with “anticoagulation forever”. All patients who undergo prolonged anticoagulation should be reassessed periodically as to the risks and benefits of continuing the treatment.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conflict of interests</span><p id="par0150" class="elsevierStylePara elsevierViewall">The author declares that there are no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres875322" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec863518" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres875323" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec863517" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Risk of recurrence and hemorrhage" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Risk–benefit balance of extending anticoagulation" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Reducing recurrent venous thromboembolism with extended anticoagulation: efficacy" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Reducing major hemorrhages with extended anticoagulation: safety" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Extended anticoagulation? In favor" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-01-02" "fechaAceptado" => "2017-02-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec863518" "palabras" => array:6 [ 0 => "Venous thromboembolism disease" 1 => "Unprovoked" 2 => "Recurrence" 3 => "Hemorrhage" 4 => "Extended anticoagulation" 5 => "Anticoagulants" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec863517" "palabras" => array:6 [ 0 => "Enfermedad tromboembólica venosa" 1 => "No provocado" 2 => "Recurrencia" 3 => "Hemorragia" 4 => "Anticoagulación extendida" 5 => "Anticoagulantes" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Venous thromboembolism disease can be considered a chronic disease because, after the first episode, there is a life-long risk of recurrence. Recurrence is a severe complication. Anticoagulation is effective while it is maintained, but when it is discontinued, the risk of new thrombotic events persists indefinitely. Clinical practice guidelines offer specific recommendations on the treatment duration for patients with provoked or recurrent disease but are not specific for those with a first unprovoked episode. The decision should be made after a careful individual assessment of the risk-benefit of anticoagulation. This article reviews the evidence in favor of extending the anticoagulation and the current therapeutic options.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La enfermedad tromboembólica venosa puede considerarse una enfermedad crónica ya que, tras un primer episodio, el riesgo de recurrencia permanece toda la vida. La recurrencia es una complicación grave. La anticoagulación es eficaz mientras se mantiene, pero al suspenderla el riesgo de nuevos eventos trombóticos persiste indefinidamente. Las guías de práctica clínica ofrecen recomendaciones específicas sobre la duración del tratamiento en pacientes con enfermedad provocada o recurrente, pero son poco precisas para aquellos con un primer episodio no provocado. La decisión debe tomarse tras una cuidadosa valoración individual del riesgo-beneficio de la anticoagulación. Este artículo repasa las evidencias a favor de prolongar la anticoagulación y las opciones terapéuticas actuales.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Please cite this article as: Fernández M. Anticoagulación extendida en la enfermedad tromboembólica venosa. A favor. Rev Clin Esp. 2017;217:359–364.</p>" ] ] "multimedia" => array:3 [ 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" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">DVT, deep vein thrombosis; PE, pulmonary embolism; VTE, venous thromboembolism.</p>" "tablatextoimagen" => array:2 [ 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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estimated general risk of recurrence<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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">In 5 years \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients with provoked VTE (proximal DVT or PE) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15% \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">Women with negative dimer-D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15% \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">Men with negative dimer-D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25% \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">Patients with idiopathic VTE (proximal DVT or PE) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1477444.png" ] ] 1 => 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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estimated general risk of recurrence \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">In 10 years \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Secondary VTE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20% \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">Severe episode of PE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30% \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">Idiopathic VTE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1477442.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Patients with a second episode of VTE have a risk of recurrence of approximately 50% greater than those who have one episode.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Estimated risk of recurrence of venous thromboembolism disease.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">HR, hazard ratio; VKA, vitamin K antagonists; 95% CI, 95% confidence interval.</p>" "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study \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">Treatment \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">Treatment duration, months \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">Major hemorrhage (events) \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">Recurrence risk vs. placebo HR (95% CI); <span class="elsevierStyleItalic">p</span> \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">Clinically relevant hemorrhage risk<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">*</span></a> vs. placebo HR (95% CI); <span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PADIS<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">29</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">VKA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.15<br>(0.51–0.90) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.96<br>(0.19–9.35) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.22 \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">RE-SONATE<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">30</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dabigatran \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.08<br>(0.02–0.25) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.92<br>(1.52–5.60) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001 \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">EINSTEIN-EXT<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">31</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rivaroxaban \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" 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">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.18<br>(0.09–0.39) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.19<br>(2.13–11.7) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 \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">AMPLIFY-EXT<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">32</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Apixaban (2.5<span class="elsevierStyleHsp" style=""></span>mg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" 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">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.19<br>(0.11–0.33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.20<br>(0.69–2.10) \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">AMPLIFY-EXT<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">32</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Apixaban (5<span class="elsevierStyleHsp" style=""></span>mg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" 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">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.20<br>(0.11–0.34) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.62<br>(0.96–2.73) \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">ASPIRE-WARFASA<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">37</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Acetylsalicylic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 (48) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.68<br>(0.51–0.90) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.50<br>(0.72–3.14) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.28 \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">SURVET<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">38</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sulodexide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.45<br>(0.27–0.92) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.97<br>(0.14–6.88) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.98 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1477443.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Major or nonmajor clinically relevant.</p> <p class="elsevierStyleNotepara" id="npar0015"><span class="elsevierStyleItalic">p</span> nd, probability value not available in the original article.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Studies in preventing the recurrence of venous thromboembolism.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">DOAs, direct oral anticoagulants; HR, hazard ratio; VKA, vitamin K antagonists; 95% CI, 95% confidence interval.</p>" "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">DOA vs. VKA \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">Number of patients \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">Overall mortality \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">Recurrence<br>(95% CI) <span class="elsevierStyleItalic">p</span> \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">Major hemorrhage<br>(95% CI) <span class="elsevierStyleItalic">p</span> \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">Clinically relevant hemorrhage<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">*</span></a><br>(95% CI) <span class="elsevierStyleItalic">p</span> \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">Intracranial<br>hemorrhage \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dabigatran<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">30</span></a><br>RE-MEDY \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2856 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.89<br>(0.47–1.71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.44<br>(0.79–2.62) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.52<br>(0.27–1.01) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.54<br>(0.41–0.71) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Events 2 vs. 4 \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">Edoxaban<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">36</span></a><br>HOKUSAI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4118 \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><td class="td" title="table-entry " align="left" valign="top">.97<br>(0.69–1.38)<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">**</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.45<br>(0.22–0.92)<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">**</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.97<br>(0.77–1.22)<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">**</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.16<br>(0.02–1.36)<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">**</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1477441.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Major or non-major clinically relevant.</p>" ] 1 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "**" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">The statistical significance (<span class="elsevierStyleItalic">p</span> value) is not available in the original article.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Direct oral anticoagulants versus vitamin K antagonists in the extended treatment of venous thromboembolism.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:38 [ 0 => array:3 [ "identificador" => "bib0195" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Pengo" 1 => "A.W. Lensing" 2 => "M.H. Prins" 3 => "A. Marchiori" 4 => "B.L. Davidson" 5 => "F. Tiozzo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa032274" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2004" "volumen" => "350" "paginaInicial" => "2257" "paginaFinal" => "2264" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15163775" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0200" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The long-term clinical course of acute deep venous thrombosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Prandoni" 1 => "A.W. Lensing" 2 => "A. Congo" 3 => "S. Cuppini" 4 => "S. Villalta" 5 => "M. Carta" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "1996" "volumen" => "125" "paginaInicial" => "1" "paginaFinal" => "7" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8644983" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0205" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk of recurrence after a first episode of symptomatic venous thromboembolism provoked by a transient risk factor: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Iorio" 1 => "C. Kearon" 2 => "E. Filippucci" 3 => "M. Marcucci" 4 => "A. Macura" 5 => "V. Pengo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archinternmed.2010.367" "Revista" => array:6 [ "tituloSerie" => "Arch Intern Med" "fecha" => "2010" "volumen" => "170" "paginaInicial" => "1710" "paginaFinal" => "1716" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20975016" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0210" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Prandoni" 1 => "F. Noventa" 2 => "A. Ghirarduzzi" 3 => "V. Pengo" 4 => "E. Bernardi" 5 => "R. Pesavento" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Haematologica" "fecha" => "2007" "volumen" => "92" "paginaInicial" => "199" "paginaFinal" => "205" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17296569" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0215" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The risk for fatal pulmonary embolism after discontinuing anticoagulant therapy for venous thromboembolism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.D. Douketis" 1 => "C.S. Gu" 2 => "S. Schulman" 3 => "A. Ghirarduzzi" 4 => "V. Pengo" 5 => "P. Prandoni" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2007" "volumen" => "147" "paginaInicial" => "766" "paginaFinal" => "774" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18056660" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0220" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Kearon" 1 => "E.A. Akl" 2 => "J. Ornelas" 3 => "A. Blaivas" 4 => "D. Jimenez" 5 => "H. Bounameaux" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.chest.2015.11.026" "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2016" "volumen" => "149" "paginaInicial" => "315" "paginaFinal" => "352" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26867832" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0225" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.V. Konstantinides" 1 => "A. Torbicki" 2 => "G. Agnelli" 3 => "N. Danchin" 4 => "D. Fitzmaurice" 5 => "N. Galie" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehu283" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2014" "volumen" => "35" "paginaInicial" => "3033" "paginaFinal" => "3069" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25173341" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0230" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Kearon" 1 => "E.A. Akl" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2013-12-512681" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2014" "volumen" => "123" "paginaInicial" => "1794" "paginaFinal" => "1801" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24497538" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0235" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants’ data from seven trials" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Boutitie" 1 => "L. Pinede" 2 => "S. Schulman" 3 => "G. Agnelli" 4 => "G. Raskob" 5 => "J. Julian" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "BMJ" "fecha" => "2011" "volumen" => "342" "paginaInicial" => "d3036" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21610040" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0240" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "D-dimer testing to determine the duration of anticoagulation therapy" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "PROLONG Investigators" "etal" => false "autores" => array:6 [ 0 => "G. Palareti" 1 => "B. Cosmi" 2 => "C. Legnani" 3 => "A. Tosetto" 4 => "C. Brusi" 5 => "A. Iorio" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa054444" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2006" "volumen" => "355" "paginaInicial" => "1780" "paginaFinal" => "1789" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17065639" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0245" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Usefulness of repeated D-dimer testing after stopping anticoagulation for a first episode of unprovoked venous thromboembolism: the PROLONG II prospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B. Cosmi" 1 => "C. Legnani" 2 => "A. Tosetto" 3 => "V. Pengo" 4 => "A. Ghirarduzzi" 5 => "S. Testa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2009-08-237354" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2010" "volumen" => "115" "paginaInicial" => "481" "paginaFinal" => "488" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19965693" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0250" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Residual vein thrombosis to establish duration of anticoagulation after a first episode of deep vein thrombosis: the duration of anticoagulation based on compression ultrasonography (DACUS) study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Siragusa" 1 => "A. Malato" 2 => "R. Anastasio" 3 => "V. Cigna" 4 => "G. Milio" 5 => "C. Amato" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2008-01-131656" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2008" "volumen" => "112" "paginaInicial" => "511" "paginaFinal" => "515" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18497320" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0255" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antiphospholipid antibodies and the risk of recurrence after a first episode of venous thromboembolism: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. Garcia" 1 => "E.A. Akl" 2 => "R. Carr" 3 => "C. Kearon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2013-04-496257" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2013" "volumen" => "122" "paginaInicial" => "817" "paginaFinal" => "824" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23760616" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0260" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Does the clinical presentation and extent of venous thrombosis predict likelihood and type of recurrence?. A patient-level meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "T. Baglin" 1 => "J. Douketis" 2 => "A. Tosetto" 3 => "M. Marcucci" 4 => "M. Cushman" 5 => "P. Kyrle" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1538-7836.2010.04022.x" "Revista" => array:6 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2010" "volumen" => "8" "paginaInicial" => "2436" "paginaFinal" => "2442" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20723032" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0265" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.A. Rodger" 1 => "S.R. Kahn" 2 => "P.S. Wells" 3 => "D.A. Anderson" 4 => "I. Chagnon" 5 => "G. Le Gal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1503/cmaj.080493" "Revista" => array:6 [ "tituloSerie" => "CMAJ" "fecha" => "2008" "volumen" => "179" "paginaInicial" => "417" "paginaFinal" => "426" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18725614" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0270" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predicting disease recurrence in patients with previous unprovoked venous thromboembolism. A proposed prediction score (DASH)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Tosetto" 1 => "A. Iorio" 2 => "M. Marcucci" 3 => "T. Baglin" 4 => "M. Cushman" 5 => "S. Eichinger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1538-7836.2012.04735.x" "Revista" => array:6 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2012" "volumen" => "10" "paginaInicial" => "1019" "paginaFinal" => "1025" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22489957" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0275" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Eichinger" 1 => "G. Heinze" 2 => "L.M. Jandeck" 3 => "P.A. Kyrle" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.109.925214" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2010" "volumen" => "121" "paginaInicial" => "1630" "paginaFinal" => "1636" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20351233" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0280" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Balancing risks and benefits of extended anticoagulant therapy for idiopathic venous thrombosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C. Kearon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1538-7836.2009.03388.x" "Revista" => array:7 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2009" "volumen" => "7" "numero" => "Suppl. 1" "paginaInicial" => "296" "paginaFinal" => "300" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19630820" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0285" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical impact of bleeding in patients taking oral anticoagulation for venous thromboembolism. A meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L.A. Linkis" 1 => "P.T. Choi" 2 => "D. Duketis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ann Inter Med" "fecha" => "2003" "volumen" => "139" "paginaInicial" => "893" "paginaFinal" => "900" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0290" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical outcome of patients with major bleeding after venous thromboembolism" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.A. Nieto" 1 => "T. Cámara" 2 => "E. González-Higueras" 3 => "N. Ruiz Jiménez" 4 => "R. Guijarro" 5 => "P.J. Marchena" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2008" "volumen" => "100" "paginaInicial" => "789" "paginaFinal" => "796" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0295" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Three months versus one year of oral anticoagulant therapy for idiopathic deep vein thrombosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "AgnelliG" 1 => "P. Prandoni" 2 => "M.G. Santamaria" 3 => "P. Bagatella" 4 => "A. Iorio" 5 => "M. Bazzan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "N Eng J Med" "fecha" => "2001" "volumen" => "345" "paginaInicial" => "165" "paginaFinal" => "169" "itemHostRev" => array:3 [ "pii" => "S0140673612607685" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0300" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Kearon" 1 => "M. Gent" 2 => "J. Hirsh" 3 => "J. Weitz" 4 => "M.J. Kovacs" 5 => "D.R. Anderson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM199903253401201" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1999" "volumen" => "340" "paginaInicial" => "901" "paginaFinal" => "907" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10089183" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0305" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term, low-intensity warfarin therapy for prevention of recurrent venous thromboembolism" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "For the PREVENT investigators" "etal" => true "autores" => array:6 [ 0 => "P.M. Ridker" 1 => "S.Z. Goldhaber" 2 => "E. Danielson" 3 => "Y. Rosenberg" 4 => "C.S. Eby" 5 => "S.R. Deitcher" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "N Eng J Med" "fecha" => "2003" "volumen" => "348" "paginaInicial" => "1425" "paginaFinal" => "1434" "itemHostRev" => array:3 [ "pii" => "S0264410X14015461" "estado" => "S300" "issn" => "0264410X" ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0310" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Duration of anticoagulation following venous thromboembolism: a meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D. Ost" 1 => "J. Tepper" 2 => "H. Mihara" 3 => "O. Lander" 4 => "R. Heinzer" 5 => "A. Fein" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.294.6.706" "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2005" "volumen" => "294" "paginaInicial" => "706" "paginaFinal" => "715" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16091573" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0315" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Schulman" 1 => "P. Lindmarker" 2 => "M. Holmstrom" 3 => "G. Larfars" 4 => "A. Carlsson" 5 => "P. Nicol" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1538-7836.2006.01795.x" "Revista" => array:7 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2006" "volumen" => "4" "paginaInicial" => "734" "paginaFinal" => "742" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16634738" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0264410X14007117" "estado" => "S300" "issn" => "0264410X" ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0320" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Kearon" 1 => "J.S. Ginsberg" 2 => "M.J. Kovacs" 3 => "D.R. Anderson" 4 => "P.S. Wells" 5 => "J.A. Julian" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa035422" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2003" "volumen" => "349" "paginaInicial" => "631" "paginaFinal" => "639" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12917299" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0325" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of outcomes after hospitalization for deep vein thrombosis or pulmonary embolism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Murin" 1 => "P.S. Romano" 2 => "R.H. White" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2002" "volumen" => "88" "paginaInicial" => "407" "paginaFinal" => "414" "itemHostRev" => array:3 [ "pii" => "S1474442213701303" "estado" => "S300" "issn" => "14744422" ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0330" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Quality of INR control and outcomes following venous thromboembolism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.M. Gallagher" 1 => "F. Vries" 2 => "J.M. Plumb" 3 => "B. Haß" 4 => "A. Clemens" 5 => "T.P. van Staa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/1076029611426139" "Revista" => array:6 [ "tituloSerie" => "Clin Appl Thromb Hemost" "fecha" => "2012" "volumen" => "18" "paginaInicial" => "370" "paginaFinal" => "378" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22275390" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0335" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Six months vs extended oral anticoagulation after a first episode of pulmonary embolism: the PADIS-PE randomized clinical trial" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "PADIS-PE Investigators" "etal" => true "autores" => array:6 [ 0 => "F. Couturaud" 1 => "O. Sanchez" 2 => "G. Pernod" 3 => "P. Mismetti" 4 => "P. Jego" 5 => "E. Duhamel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2015.7046" "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2015" "volumen" => "314" "paginaInicial" => "31" "paginaFinal" => "40" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26151264" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0340" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Extended use of dabigatran, warfarin, or placebo in venous thromboembolism" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "RE-MEDY trial investigators RE-SONATE trial investigators" "etal" => true "autores" => array:6 [ 0 => "S. Schulman" 1 => "C. Kearon" 2 => "A.K. Kakkar" 3 => "S. Schellong" 4 => "H. Eriksson" 5 => "D. Baanstra" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1113697" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2013" "volumen" => "368" "paginaInicial" => "709" "paginaFinal" => "718" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23425163" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0345" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oral rivaroxaban after symptomatic venous thromboembolism: the continued treatment study (EINSTEIN-extension study)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E. Romualdi" 1 => "M.P. Donadini" 2 => "W. Agerno" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Expert Rev CardiovascTher" "fecha" => "2011" "volumen" => "9" "paginaInicial" => "841" "paginaFinal" => "844" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0350" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Apixaban for extended treatment of venous thromboembolism" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "for the AMPLIFY-EXT Investigators" "etal" => true "autores" => array:6 [ 0 => "G. Agnelli" 1 => "H.R. Buller" 2 => "A. Cohen" 3 => "M. Curto" 4 => "A.S. Gallus" 5 => "M. Johnson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1207541" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2013" "volumen" => "368" "paginaInicial" => "699" "paginaFinal" => "708" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23216615" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0355" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of anticoagulant therapy for the treatment of acute cancer-associated thrombosis: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Carrier" 1 => "C. Cameron" 2 => "A. Delluc" 3 => "L. Castellucci" 4 => "A.A. Khorana" 5 => "A.Y. Lee" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.thromres.2014.09.039" "Revista" => array:6 [ "tituloSerie" => "Thromb Res" "fecha" => "2014" "volumen" => "134" "paginaInicial" => "1214" "paginaFinal" => "1219" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25457583" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0360" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.Y. Lee" 1 => "P.W. Kamphuisen" 2 => "G. Meyer" 3 => "R. Bauersachs" 4 => "M.S. Janas" 5 => "M.F. Jarner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2015.9243" "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2015" "volumen" => "314" "paginaInicial" => "677" "paginaFinal" => "686" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26284719" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0365" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology and management of bleeding in patients using vitamin K antagonists" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M. Levi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1538-7836.2009.03389.x" "Revista" => array:7 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2009" "volumen" => "7" "numero" => "Suppl. 1" "paginaInicial" => "103" "paginaFinal" => "106" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19630779" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0370" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Extended duration of anticoagulation with edoxaban in patients with venous thromboembolism: a post- hoc analysis of the Hokusai-VTE study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Raskob" 1 => "W. Ageno" 2 => "A.T. Cohen" 3 => "M.P. Brekelmans" 4 => "M.A. Grosso" 5 => "A. Segers" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Lancet Haematol" "fecha" => "2016" "volumen" => "3" "paginaInicial" => "228" "paginaFinal" => "236" ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0375" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "INSPIRE Study Investigators (International Collaboration of Aspirin Trials for Recurrent Venous Thromboembolism)" "etal" => true "autores" => array:6 [ 0 => "J. Simes" 1 => "C. Becattini" 2 => "G. Agnelli" 3 => "J.W. Eikelboom" 4 => "A.C. Kirby" 5 => "R. Mister" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.114.008828" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2014" "volumen" => "130" "paginaInicial" => "1062" "paginaFinal" => "1071" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25156992" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0380" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The sulodexide in secondary prevention of recurrent deep vein thrombosis (SURVET) study: a multicenter, randomized, double blind, placebo- controlled trial" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "on belhaf of the SURVET Study investigators" "etal" => true "autores" => array:6 [ 0 => "G.M. Andreozzi" 1 => "A.A. Bignamini" 2 => "G. Davi" 3 => "G. Palareti" 4 => "J. Matuska" 5 => "M. Holy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.115.016930" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2015" "volumen" => "132" "paginaInicial" => "1891" "paginaFinal" => "1897" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26408273" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/22548874/0000021700000006/v1_201707280038/S225488741730053X/v1_201707280038/en/main.assets" "Apartado" => array:4 [ "identificador" => "66381" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Pros and cons" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/22548874/0000021700000006/v1_201707280038/S225488741730053X/v1_201707280038/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S225488741730053X?idApp=WRCEE" ]
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