Early, real-world experience with direct oral anticoagulants in the treatment of intermediate-high risk acute pulmonary embolism | Revista Portuguesa de Cardiologia (English edition)

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"Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Experiência inicial com os anticoagulantes orais diretos no tratamento do tromboembolismo pulmonar agudo de risco intermédio-alto: dados do mundo real" ] ] "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" => 1064 "Ancho" => 1250 "Tamanyo" => 102637 ] ] "descripcion" => array:1 [ "en" => "Study population flowchart. CONV: conventional anticoagulation; DOAC: direct oral anticoagulant; PE: pulmonary embolism." ] ] ] "textoCompleto" => "IntroductionPulmonary embolism (PE) is a common disease, with an estimated annual incidence of 70 cases per 100 000.<a class="elsevierStyleCrossRefs" href="#bib0105">1,2</a> This condition can be life-threatening if not treated rapidly and appropriately and often leads to chronic disease and disability.<a class="elsevierStyleCrossRef" href="#bib0115">3</a> Mortality from PE, 15% at three months, exceeds that for acute myocardial infarction.<a class="elsevierStyleCrossRef" href="#bib0120">4</a> Risk stratification helps to optimize the selection of patients who will benefit from more aggressive therapy, such as thrombolysis or embolectomy, in addition to anticoagulation.<a class="elsevierStyleCrossRef" href="#bib0120">4</a> High-risk patients are also most susceptible to the dreaded complication of chronic thromboembolic pulmonary hypertension.<a class="elsevierStyleCrossRef" href="#bib0120">4</a> In order to predict early (in-hospital or 30-day) outcomes, both PE-related risk and the patient's clinical status and comorbidities should be taken into consideration, and can be measured using risk scores such as the pulmonary embolism severity index (PESI).<a class="elsevierStyleCrossRef" href="#bib0125">5</a> Intermediate-high risk patients have positive cardiac laboratory biomarkers, signs of right ventricular (RV) dysfunction on an imaging test and PESI class III-V or simplified PESI (sPESI) ≥1.The conventional PE treatment approach consists of a parenteral anticoagulant such as enoxaparin for at least five days, followed by a vitamin K antagonist (VKA) such as warfarin, and continued for at least three months.<a class="elsevierStyleCrossRef" href="#bib0130">6</a> Although effective, this regimen is challenging, as enoxaparin requires daily subcutaneous injections and VKAs require close monitoring and dose adjustment.<a class="elsevierStyleCrossRef" href="#bib0135">7</a> The recently developed direct oral anticoagulants (DOACs), which inhibit factor Xa or thrombin, can overcome these limitations.<a class="elsevierStyleCrossRef" href="#bib0140">8</a> DOACs have been tested against conventional therapy in large phase III studies for the treatment of PE: EINSTEIN-PE for rivaroxaban, RE-COVER and RE-COVER II for dabigatran, AMPLIFY for apixaban and Hokusai-VTE for edoxaban.<a class="elsevierStyleCrossRefs" href="#bib0105">1,9–11</a> Rivaroxaban and apixaban allow for a single drug regimen, eliminating the need for initial parenteral anticoagulation, while dabigatran and edoxaban are initiated after a course of parenteral therapy.<a class="elsevierStyleCrossRef" href="#bib0105">1</a> In all these studies, DOACs were shown to be at least as effective as VKAs for preventing recurrent VTE and VTE-related death, and demonstrated a similar or reduced incidence of major and/or major plus non-major clinically relevant bleeding (the principal safety outcome events), compared with conventional treatment.<a class="elsevierStyleCrossRef" href="#bib0160">12</a> All DOACs have been approved for the treatment of PE and are recommended as alternatives to standard therapy in international guidelines.<a class="elsevierStyleCrossRefs" href="#bib0125">5,13</a> Although these recommendations are based on randomized clinical trials (RCTs),<a class="elsevierStyleCrossRefs" href="#bib0105">1,9–11</a> the real-world use of DOACs compared with warfarin is less clear. Phase III trials have selective inclusion criteria, and the reproducibility of their findings needs to be assessed in broader patient populations like those seen in routine clinical practice.<a class="elsevierStyleCrossRef" href="#bib0170">14</a> Safety outcomes in clinical practice may diverge from trials for several reasons, including selective inclusion criteria and the limited duration of follow-up in the latter.<a class="elsevierStyleCrossRef" href="#bib0175">15</a> Also, intermediate-high risk PE patients represent a particular subset of PE patients with a poorer prognosis,<a class="elsevierStyleCrossRef" href="#bib0180">16</a> but are under-represented in RCTs and are not reported as an independent group in any of the PE RCTs. In this study we aimed to report the efficacy and safety of a DOAC-based regimen compared with a conventional treatment approach in patients admitted to a cardiac care unit with intermediate-high risk PE.MethodsWe conducted a single-center, retrospective cohort study of patients with confirmed PE treated with the standard anticoagulation regimen (CONV) or with DOACs. The study was approved by the local ethics committee and was in accordance with the 2008 Declaration of Helsinki.Study populationBetween January 2010 and August 2015, 116 consecutive patients admitted with intermediate-high risk PE were included. Patients with intermediate-high risk PE were defined as those with positive myocardial lesion markers (troponin I), right ventricular dysfunction (assessed by echocardiography), and PESI class III-V or sPESI ≥1. After the introduction of DOACs in our hospital's pharmacy (in August 2013), all PE patients with indication and without contraindication were started on DOACs for treatment of acute PE. We retrospectively selected a historical cohort of PE patients with similar clinical characteristics treated with a CONV approach between February 2010 and September 2014. A total of 57 patients initially treated by thrombolysis were excluded from the analysis (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The choice of DOAC was left to the discretion of the attending physician. The treatment regimens were as recommended by the manufacturer.<a class="elsevierStyleCrossRef" href="#bib0105">1</a> Discharge reports were used to obtain information on demographics, personal history and laboratory workup. All patients were followed for up to three months after discharge.ExposurePatients with intermediate-high risk PE were managed either with a conventional approach (enoxaparin followed by VKA) (CONV group, n=35) or with DOACs (DOAC group, n=24) (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>).EndpointsThe primary efficacy endpoints were (i) death, (ii) recurrent PE, (iii) echocardiographically-estimated pulmonary artery systolic pressure (PASP) at discharge, (iv) right ventricular function at discharge and (v) length of stay. Death was sub-classified as being PE-related, bleeding-related, or from other causes. Recurrent PE was defined as the new onset of symptoms confirmed by diagnostic testing. PASP and right ventricular function were obtained from the discharge echocardiogram report. The primary safety endpoint was major bleeding. Major bleeding was defined as overt bleeding associated with a fall in hemoglobin of 2g/l or more; a transfusion of two or more units of packed red blood cells; critical site bleeding (intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal); or fatal bleeding (defined using the International Society on Thrombosis and Haemostasis criteria).<a class="elsevierStyleCrossRef" href="#bib0185">17</a>Statistical analysisData are shown as means ± standard deviation (SD) for continuous variables and absolute and relative frequencies (%) for categorical variables. The paired-sample t test and the sign test were used to compare treatment strategies. All analyses were performed with STATA 12.0 (StataCorp LP, TX, USA). A two-sided p<0.05 was considered statistically significant.ResultsThe clinical characteristics of the study population are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Of the 59 patients included, 35 (59%) were managed with a CONV approach and 24 (40%) with a DOAC approach. The mean patient age was 62±19 years (median 58, range 29-87) and 61±17 years (median 57, range 24-78) for the CONV and DOAC groups, respectively (p=0.770). No differences were found between the CONV and DOAC groups in gender or laboratory tests. Creatinine clearance was similar (p=0.881). Regarding cardiac biomarkers, no significant differences were found between the two groups, although B-type natriuretic peptide (BNP) levels were numerically higher in the CONV group (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>In the DOAC group, three cases of PE were provoked (cancer, surgery and prolonged immobilization), while 11 in the CONV group were provoked (childbirth, chronic pulmonary embolism, cancer, surgery and immobilization). None of the patients in the DOAC group had a prior history of PE or known thrombophilia, while in the CONV group, two patients had a prior PE (these patients had a history of cancer); none had known thrombophilia.OutcomesThere were four in-hospital death in the CONV group, whereas no deaths occurred in the DOAC group. No recurrent PE was recorded in any of the groups during admission or during the three-month follow-up. Regarding the safety outcome, no major bleeding events were observed in either group. There was a statistically significant difference (p=0.002) between the CONV (4.7±2.4) and the DOAC (3.0±1.5) groups in length of stay. No differences were found regarding echocardiographic parameters at discharge, including PASP (p=0.471) and right ventricular systolic function (p=0.684) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>DiscussionThe demand for real-world data in addition to clinical trial data is increasing.<a class="elsevierStyleCrossRef" href="#bib0185">17</a> Non-interventional studies are crucial for obtaining a different perspective on the safety and effectiveness of drugs when used in routine clinical practice. Studies performed with real-world populations complement the outcomes of pivotal trials through the use of unselected real-world populations and conditions. Here, we report a real-world observational study analyzing the use of DOACs in the treatment of intermediate-high risk PE. We show that the efficacy and safety of such a strategy is comparable to the conventional, VKA-based approach and that length of stay may be reduced with a DOAC-based regimen, a critical finding in the intensive care unit setting.DOACs have been tested against conventional therapy for the treatment of PE in large phase III trials: EINSTEIN-PE for rivaroxaban, RE-COVER and RE-COVER II for dabigatran, AMPLIFY for apixaban and Hokusai-VTE for edoxaban. In all these these trials, DOACs were shown to be at least as effective as VKAs for preventing recurrent VTE and VTE-related death, and demonstrated a similar or reduced incidence of major and/or major plus non-major clinically relevant bleeding (principal safety outcome events), compared with conventional treatment. A meta-analysis of the phase III VTE trials concluded that DOACs and VKAs have similar efficacy in the treatment of acute symptomatic VTE, a finding that is consistent in key clinical subgroups, and concluded that treatment with a DOAC significantly reduces the risks of major bleeding.<a class="elsevierStyleCrossRef" href="#bib0190">18</a> However, intermediate-high risk PE defines a population at higher risk of both thrombotic and bleeding complications that is not well represented in most trials of DOACs in VTE, as most do not include information on cardiac necrosis markers or right ventricular function. Therefore, real-world treatment data on this specific stratum of PE patients are paramount.Our study shows similar rates of death and recurrent PE during hospital stay and follow-up in both groups. Additionally, no major bleeding events were observed within three months of beginning treatment. These results highlight the safety of anticoagulation in this population and are consistent with those of RCTs on DOACs, in which the incidence of major bleeding was around 1% for all studies. In other studies in the real-world setting, the risk of bleeding related to DOACs was similar to that for warfarin.<a class="elsevierStyleCrossRef" href="#bib0195">19</a> Reassuringly, the findings of our study are in line with those in the literature for patients treated in routine clinical practice.<a class="elsevierStyleCrossRef" href="#bib0200">20</a>Another important point relates to the efficacy of DOACs for thrombus disintegration in intermediate-high risk PE patients, who may have a higher thrombotic burden in the lung vasculature. It is suggested that DOACs may be even more effective than warfarin in patients with markers of RV dysfunction, as shown in the Hokusai-VTE trial. However, in this trial RV dysfunction was analyzed only by elevation of BNP, a criterion that does not reflect usual clinical practice, which is to integrate laboratory, imaging and clinical risk score data.<a class="elsevierStyleCrossRef" href="#bib0155">11</a>In line with the evidence from RCTs,<a class="elsevierStyleCrossRef" href="#bib0155">11</a> we found no differences between the groups in two surrogate markers of right ventricular afterload, echocardiographically-estimated PASP and right ventricular function. It is therefore plausible that thrombus resolution rate and extent would be similar in both treatment regimens.We found a significant difference between the two groups in length of stay, which was more than one day shorter in the DOAC group. This finding is probably due to the fact that the maximum anticoagulant effect of warfarin is only achieved 3-5 days after the first dose, and dosage needs to be adjusted according to the international normalized ratio (INR) before the patient is discharged. With the DOAC treatment strategy, after the patient is stabilized in terms of heart failure, oxygen saturation and pain (which frequently occurs before the target INR is achieved), there is no need to prolong hospitalization.Among study limitations, we highlight the study's retrospective design and the use of a historical cohort of patients treated with VKAs, the small number of patients enrolled, related to the early experience using DOACS in treating PE, and the absence of thrombotic or bleeding events, a fact that reflects the very good prognosis of correctly treated PE, even those of intermediate-high risk.ConclusionsThe adoption of a DOAC treatment strategy in intermediate-high risk PE patients in this typical real-world cohort was associated with comparable efficacy and safety to the conventional treatment regimen of parenteral anticoagulant plus warfarin. Importantly, length of stay was significantly reduced. No differences were found regarding right ventricular function markers at discharge. Further studies in larger cohorts will help to clarify the use of DOACs in this challenging PE population.Ethical disclosuresProtection of human and animal subjectsThe authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association (Declaration of Helsinki).Confidentiality of dataThe authors declare that they have followed the protocols of their work center on the publication of patient data.Right to privacy and informed consentThe authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.Conflict of interestR.B. has received speaker fees from BMS/Pfizer, Bayer and Daiichi-Sankyo, investigator fees from Bayer and personal fees (advisory board) from BMS/Pfizer and Bayer.S.M. has received speaker fees from BMS/Pfizer and Bayer, investigator fees from Bayer and personal fees (advisory board) from Bayer.P.M. has received speaker fees from BMS/Pfizer, Bayer, Daiichi-Sankyo and Boheringer-Ingelheim, investigator fees from Bayer, Boheringer-Ingelheim and Daiichi-Sankyo and personal fees (advisory board) from BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres957253" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec928581" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres957252" "titulo" => "Resumo" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introdução" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusões" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec928582" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Exposure" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Endpoints" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Outcomes" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Conclusions" ] 10 => array:3 [ "identificador" => "sec0055" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Right to privacy and informed consent" ] ] ] 11 => array:2 [ "identificador" => "sec0075" "titulo" => "Conflict of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-11-03" "fechaAceptado" => "2017-01-12" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec928581" "palabras" => array:6 [ 0 => "Anticoagulants" 1 => "Venous thromboembolism" 2 => "Real world" 3 => "Pulmonary embolism" 4 => "Intermediate-high risk" 5 => "Warfarin" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec928582" "palabras" => array:6 [ 0 => "Anticoagulantes" 1 => "Tromboembolismo venoso" 2 => "Mundo real" 3 => "Embolia pulmonar" 4 => "Risco intermédio a elevado" 5 => "Varfarina" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionIntermediate-high risk pulmonary embolism (IHR-PE) has a poor prognosis, but is under-represented in trials of direct oral anticoagulants (DOACs) in venous thromboembolic disease (VTE). We aimed to assess whether the administration of DOACs was equivalent to the conventional (CONV) treatment of low-molecular weight heparin bridged with warfarin for treating IHR-PE. MethodsWe conducted a retrospective cohort study including 59 consecutive patients admitted with IHR-PE and followed for up to three months after discharge. Two groups were created based on the anticoagulant strategy: CONV (n=35) and DOAC (n=24). The efficacy endpoints were death, recurrent PE, estimated pulmonary artery systolic pressure (PASP), right ventricular systolic function (RVSF) at discharge, and length of stay; the safety endpoint was major bleeding. ResultsThe two groups were similar regarding demographics, PE etiology and markers of clinical severity. There were four in-hospital deaths in the CONV group and none in the DOAC group. No recurrent PE or major bleeding event was recorded in either group. At discharge, neither PASP nor RVSF was different between the groups. Patients in the DOAC group were discharged 1.7 days earlier on average than patients in the CONV group (4.7±2.4 vs. 3.0±1.5 days, p=0.002). ConclusionsThe adoption of a DOAC treatment strategy in this real-world cohort of IHR-PE patients was associated with similar efficacy and safety to the CONV approach. The fact that monitoring of anticoagulation effect was unnecessary probably led to the significant reduction in length of stay." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "pt" => array:3 [ "titulo" => "Resumo" "resumen" => "IntroduçãoO tromboembolismo pulmonar de risco intermédio-elevado (TEP-IE) condiciona um prognóstico mais agravado, mas se encontra sub-representado nos ensaios dos anticoagulantes orais diretos (ACOd) na doença tromboembólica venosa (DTV). Avaliamos se a administração de ACOd foi equivalente à estratégia terapêutica convencional (CONV) (heparina de baixo peso molecular (HBPM) + varfarina) no tratamento do TEP-IE. MétodosFez-se um estudo de coorte retrospetivo com 59 doentes consecutivos internados por TEP-IE, seguidos até três meses após a alta. Criaram-se dois grupos, baseados na estratégia terapêutica anticoagulante: CONV (n = 35) e DOAC (n = 24) (ACOd). Os desfechos de eficácia foram a morte, o TEP recorrente, a pressão sistólica na artéria pulmonar (PSAP), a função ventricular direita (FVD) e a duração do internamento; o desfecho de segurança foi a hemorragia major. ResultadosOs grupos eram comparáveis relativamente aos aspetos demográficos, à etiologia do TEP e aos marcadores de gravidade clínica. Ocorreram quatro mortes intra-hospitalares no grupo CONV e nenhuma no grupo DOAC. Nenhum evento de TEP recorrente ou hemorragia major ocorreu em qualquer dos grupos. À data de alta, quer a PSAP quer a FVD não diferiram entre os dois grupos. A alta ocorreu 1,7 dia mais cedo no grupo DOAC do que no grupo CONV (4,7±2,4 versus 3,0±1,5 dias, p = 0,002). ConclusõesA adoção de uma estratégia de tratamento com ACOd associou-se a um perfil de eficácia e segurança semelhante à abordagem convencional. A ausência da necessidade de monitoração do efeito anticoagulante provavelmente motivou a redução na duração de internamento." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introdução" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusões" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "Both authors contributed equally to this work" "identificador" => "fn1" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1064 "Ancho" => 1250 "Tamanyo" => 102637 ] ] "descripcion" => array:1 [ "en" => "Study population flowchart. CONV: conventional anticoagulation; DOAC: direct oral anticoagulant; PE: pulmonary embolism." ] ] 1 => 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:2 [ "leyenda" => "BNP: B-type natriuretic peptide; CK: creatine kinase; CONV: conventional anticoagulation group; CrCl: creatinine clearance; CTPA: computed tomography pulmonary angiography; DOAC: direct oral anticoagulant group; PE: pulmonary embolism; TnI: troponin I; VTE: venous thromboembolism." "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">Variable \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">CONV (n=35) \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">DOAC (n=24) \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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age, years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62±19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">61±17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.770 \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">Male, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-- \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"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">CrCl, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><30 ml/min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (2.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 (0) \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">30 to <50 ml/min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (14.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (8.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.881 \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">50 to <80 ml/min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (28.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (41.7) \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">≥80 ml/min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19 (54.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (50) \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" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">Diagnostic method and classification</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CTPA, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-- \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"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">Laboratory tests</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D-dimers, μg/ml (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.93 (30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.44 (23) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.897 \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">BNP, pg/ml (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">420.17 (23) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">163.46 (11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.095 \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">TnI, ng/ml (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.75 (35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.57 (24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.717 \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">Myoglobin, ng/ml (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">116.09 (35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">53.79 (24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.138 \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">CK, U/L (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">128.73 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90.88 (24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.337 \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">CK-MB, U/L (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.45 (35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.73 (24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.778 \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"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">PE risk factors, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Unprovoked \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 (49) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 (87) \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">Provoked \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11 (31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.030 \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">Not reported \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \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">Previous VTE, n \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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">Active cancer, n \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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">Known thrombophilia, n \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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">Pregnancy, n \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">-- \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1621934.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Demographic and clinical characteristics of the study population." ] ] 2 => 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:2 [ "leyenda" => "CONV: conventional anticoagulation group; DOAC: direct oral anticoagulant group; LOS: length of stay; PASP: pulmonary artery systolic pressure; PE: pulmonary embolism; RV: right ventricular." "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">Variables \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">CONV (n=35) \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">DOAC (n=24) \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">Efficacy endpoints</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Death, n \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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 \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">Recurrent PE, n \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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 \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">PASP (mmHg), mean ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44.9±8.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">41.2±9.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.471 \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"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">RV function, n (%)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10/24 (41.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7/23 (30.4) \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">Mildly depressed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7/24 (29.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9/23 (39.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.684 \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">Moderately/severely depressed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7/24 (29.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7/23 (30.4) \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">LOS (days), mean ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.7 ± 2.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.0 ± 1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.002 \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"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top">Safety endpoint</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Major bleeding, n \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" 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 \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></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1621935.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical outcomes during the treatment period." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0105" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "EINSTEIN–PE Investigators, Büller HR, Prins MH, Lensin AW, et al. 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Original Article

Early, real-world experience with direct oral anticoagulants in the treatment of intermediate-high risk acute pulmonary embolism

Experiência inicial com os anticoagulantes orais diretos no tratamento do tromboembolismo pulmonar agudo de risco intermédio-alto: dados do mundo real

Sónia Martins Santosa,1, Susana Cunhaa,1, Rui Baptistab,c,

Corresponding author

rui.baptista@fmed.uc.pt

Corresponding author.

, Sílvia Monteirob, Pedro Monteirob,c, Francisco Gonçalvesb, Mariano Pêgob

a Serviço de Medicina 2, Centro Hospitalar de Leiria, Hospital de Leiria, Leiria, Portugal

b Serviço de Cardiologia A, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

c Faculty of Medicine, University of Coimbra, Coimbra, Portugal

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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Study population flowchart&#46; CONV&#58; conventional anticoagulation&#59; DOAC&#58; direct oral anticoagulant&#59; PE&#58; pulmonary embolism&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Pulmonary embolism &#40;PE&#41; is a common disease&#44; with an estimated annual incidence of 70 cases per 100&#160;000&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1&#44;2</span></a> This condition can be life-threatening if not treated rapidly and appropriately and often leads to chronic disease and disability&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> Mortality from PE&#44; 15&#37; at three months&#44; exceeds that for acute myocardial infarction&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> Risk stratification helps to optimize the selection of patients who will benefit from more aggressive therapy&#44; such as thrombolysis or embolectomy&#44; in addition to anticoagulation&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> High-risk patients are also most susceptible to the dreaded complication of chronic thromboembolic pulmonary hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> In order to predict early &#40;in-hospital or 30-day&#41; outcomes&#44; both PE-related risk and the patient&#39;s clinical status and comorbidities should be taken into consideration&#44; and can be measured using risk scores such as the pulmonary embolism severity index &#40;PESI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> Intermediate-high risk patients have positive cardiac laboratory biomarkers&#44; signs of right ventricular &#40;RV&#41; dysfunction on an imaging test and PESI class III-V or simplified PESI &#40;sPESI&#41; &#8805;1&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The conventional PE treatment approach consists of a parenteral anticoagulant such as enoxaparin for at least five days&#44; followed by a vitamin K antagonist &#40;VKA&#41; such as warfarin&#44; and continued for at least three months&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> Although effective&#44; this regimen is challenging&#44; as enoxaparin requires daily subcutaneous injections and VKAs require close monitoring and dose adjustment&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> The recently developed direct oral anticoagulants &#40;DOACs&#41;&#44; which inhibit factor Xa or thrombin&#44; can overcome these limitations&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">8</span></a> DOACs have been tested against conventional therapy in large phase III studies for the treatment of PE&#58; EINSTEIN-PE for rivaroxaban&#44; RE-COVER and RE-COVER II for dabigatran&#44; AMPLIFY for apixaban and Hokusai-VTE for edoxaban&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1&#44;9&#8211;11</span></a> Rivaroxaban and apixaban allow for a single drug regimen&#44; eliminating the need for initial parenteral anticoagulation&#44; while dabigatran and edoxaban are initiated after a course of parenteral therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a> In all these studies&#44; DOACs were shown to be at least as effective as VKAs for preventing recurrent VTE and VTE-related death&#44; and demonstrated a similar or reduced incidence of major and&#47;or major plus non-major clinically relevant bleeding &#40;the principal safety outcome events&#41;&#44; compared with conventional treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> All DOACs have been approved for the treatment of PE and are recommended as alternatives to standard therapy in international guidelines&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">5&#44;13</span></a> Although these recommendations are based on randomized clinical trials &#40;RCTs&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1&#44;9&#8211;11</span></a> the real-world use of DOACs compared with warfarin is less clear&#46; Phase III trials have selective inclusion criteria&#44; and the reproducibility of their findings needs to be assessed in broader patient populations like those seen in routine clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">14</span></a> Safety outcomes in clinical practice may diverge from trials for several reasons&#44; including selective inclusion criteria and the limited duration of follow-up in the latter&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a> Also&#44; intermediate-high risk PE patients represent a particular subset of PE patients with a poorer prognosis&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a> but are under-represented in RCTs and are not reported as an independent group in any of the PE RCTs&#46; In this study we aimed to report the efficacy and safety of a DOAC-based regimen compared with a conventional treatment approach in patients admitted to a cardiac care unit with intermediate-high risk PE&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">We conducted a single-center&#44; retrospective cohort study of patients with confirmed PE treated with the standard anticoagulation regimen &#40;CONV&#41; or with DOACs&#46; The study was approved by the local ethics committee and was in accordance with the 2008 Declaration of Helsinki&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study population</span><p id="par0020" class="elsevierStylePara elsevierViewall">Between January 2010 and August 2015&#44; 116 consecutive patients admitted with intermediate-high risk PE were included&#46; Patients with intermediate-high risk PE were defined as those with positive myocardial lesion markers &#40;troponin I&#41;&#44; right ventricular dysfunction &#40;assessed by echocardiography&#41;&#44; and PESI class III-V or sPESI &#8805;1&#46; After the introduction of DOACs in our hospital&#39;s pharmacy &#40;in August 2013&#41;&#44; all PE patients with indication and without contraindication were started on DOACs for treatment of acute PE&#46; We retrospectively selected a historical cohort of PE patients with similar clinical characteristics treated with a CONV approach between February 2010 and September 2014&#46; A total of 57 patients initially treated by thrombolysis were excluded from the analysis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The choice of DOAC was left to the discretion of the attending physician&#46; The treatment regimens were as recommended by the manufacturer&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a> Discharge reports were used to obtain information on demographics&#44; personal history and laboratory workup&#46; All patients were followed for up to three months after discharge&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Exposure</span><p id="par0030" class="elsevierStylePara elsevierViewall">Patients with intermediate-high risk PE were managed either with a conventional approach &#40;enoxaparin followed by VKA&#41; &#40;CONV group&#44; n&#61;35&#41; or with DOACs &#40;DOAC group&#44; n&#61;24&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Endpoints</span><p id="par0035" class="elsevierStylePara elsevierViewall">The primary efficacy endpoints were &#40;i&#41; death&#44; &#40;ii&#41; recurrent PE&#44; &#40;iii&#41; echocardiographically-estimated pulmonary artery systolic pressure &#40;PASP&#41; at discharge&#44; &#40;iv&#41; right ventricular function at discharge and &#40;v&#41; length of stay&#46; Death was sub-classified as being PE-related&#44; bleeding-related&#44; or from other causes&#46; Recurrent PE was defined as the new onset of symptoms confirmed by diagnostic testing&#46; PASP and right ventricular function were obtained from the discharge echocardiogram report&#46; The primary safety endpoint was major bleeding&#46; Major bleeding was defined as overt bleeding associated with a fall in hemoglobin of 2<span class="elsevierStyleHsp" style=""></span>g&#47;l or more&#59; a transfusion of two or more units of packed red blood cells&#59; critical site bleeding &#40;intracranial&#44; intraspinal&#44; intraocular&#44; pericardial&#44; intra-articular&#44; intramuscular with compartment syndrome&#44; or retroperitoneal&#41;&#59; or fatal bleeding &#40;defined using the International Society on Thrombosis and Haemostasis criteria&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Data are shown as means &#177; standard deviation &#40;SD&#41; for continuous variables and absolute and relative frequencies &#40;&#37;&#41; for categorical variables&#46; The paired-sample t test and the sign test were used to compare treatment strategies&#46; All analyses were performed with STATA 12&#46;0 &#40;StataCorp LP&#44; TX&#44; USA&#41;&#46; A two-sided p&#60;0&#46;05 was considered statistically significant&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">The clinical characteristics of the study population are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Of the 59 patients included&#44; 35 &#40;59&#37;&#41; were managed with a CONV approach and 24 &#40;40&#37;&#41; with a DOAC approach&#46; The mean patient age was 62&#177;19 years &#40;median 58&#44; range 29-87&#41; and 61&#177;17 years &#40;median 57&#44; range 24-78&#41; for the CONV and DOAC groups&#44; respectively &#40;p&#61;0&#46;770&#41;&#46; No differences were found between the CONV and DOAC groups in gender or laboratory tests&#46; Creatinine clearance was similar &#40;p&#61;0&#46;881&#41;&#46; Regarding cardiac biomarkers&#44; no significant differences were found between the two groups&#44; although B-type natriuretic peptide &#40;BNP&#41; levels were numerically higher in the CONV group &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">In the DOAC group&#44; three cases of PE were provoked &#40;cancer&#44; surgery and prolonged immobilization&#41;&#44; while 11 in the CONV group were provoked &#40;childbirth&#44; chronic pulmonary embolism&#44; cancer&#44; surgery and immobilization&#41;&#46; None of the patients in the DOAC group had a prior history of PE or known thrombophilia&#44; while in the CONV group&#44; two patients had a prior PE &#40;these patients had a history of cancer&#41;&#59; none had known thrombophilia&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Outcomes</span><p id="par0055" class="elsevierStylePara elsevierViewall">There were four in-hospital death in the CONV group&#44; whereas no deaths occurred in the DOAC group&#46; No recurrent PE was recorded in any of the groups during admission or during the three-month follow-up&#46; Regarding the safety outcome&#44; no major bleeding events were observed in either group&#46; There was a statistically significant difference &#40;p&#61;0&#46;002&#41; between the CONV &#40;4&#46;7&#177;2&#46;4&#41; and the DOAC &#40;3&#46;0&#177;1&#46;5&#41; groups in length of stay&#46; No differences were found regarding echocardiographic parameters at discharge&#44; including PASP &#40;p&#61;0&#46;471&#41; and right ventricular systolic function &#40;p&#61;0&#46;684&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">The demand for real-world data in addition to clinical trial data is increasing&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> Non-interventional studies are crucial for obtaining a different perspective on the safety and effectiveness of drugs when used in routine clinical practice&#46; Studies performed with real-world populations complement the outcomes of pivotal trials through the use of unselected real-world populations and conditions&#46; Here&#44; we report a real-world observational study analyzing the use of DOACs in the treatment of intermediate-high risk PE&#46; We show that the efficacy and safety of such a strategy is comparable to the conventional&#44; VKA-based approach and that length of stay may be reduced with a DOAC-based regimen&#44; a critical finding in the intensive care unit setting&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">DOACs have been tested against conventional therapy for the treatment of PE in large phase III trials&#58; EINSTEIN-PE for rivaroxaban&#44; RE-COVER and RE-COVER II for dabigatran&#44; AMPLIFY for apixaban and Hokusai-VTE for edoxaban&#46; In all these these trials&#44; DOACs were shown to be at least as effective as VKAs for preventing recurrent VTE and VTE-related death&#44; and demonstrated a similar or reduced incidence of major and&#47;or major plus non-major clinically relevant bleeding &#40;principal safety outcome events&#41;&#44; compared with conventional treatment&#46; A meta-analysis of the phase III VTE trials concluded that DOACs and VKAs have similar efficacy in the treatment of acute symptomatic VTE&#44; a finding that is consistent in key clinical subgroups&#44; and concluded that treatment with a DOAC significantly reduces the risks of major bleeding&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">18</span></a> However&#44; intermediate-high risk PE defines a population at higher risk of both thrombotic and bleeding complications that is not well represented in most trials of DOACs in VTE&#44; as most do not include information on cardiac necrosis markers or right ventricular function&#46; Therefore&#44; real-world treatment data on this specific stratum of PE patients are paramount&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Our study shows similar rates of death and recurrent PE during hospital stay and follow-up in both groups&#46; Additionally&#44; no major bleeding events were observed within three months of beginning treatment&#46; These results highlight the safety of anticoagulation in this population and are consistent with those of RCTs on DOACs&#44; in which the incidence of major bleeding was around 1&#37; for all studies&#46; In other studies in the real-world setting&#44; the risk of bleeding related to DOACs was similar to that for warfarin&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">19</span></a> Reassuringly&#44; the findings of our study are in line with those in the literature for patients treated in routine clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Another important point relates to the efficacy of DOACs for thrombus disintegration in intermediate-high risk PE patients&#44; who may have a higher thrombotic burden in the lung vasculature&#46; It is suggested that DOACs may be even more effective than warfarin in patients with markers of RV dysfunction&#44; as shown in the Hokusai-VTE trial&#46; However&#44; in this trial RV dysfunction was analyzed only by elevation of BNP&#44; a criterion that does not reflect usual clinical practice&#44; which is to integrate laboratory&#44; imaging and clinical risk score data&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">In line with the evidence from RCTs&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a> we found no differences between the groups in two surrogate markers of right ventricular afterload&#44; echocardiographically-estimated PASP and right ventricular function&#46; It is therefore plausible that thrombus resolution rate and extent would be similar in both treatment regimens&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">We found a significant difference between the two groups in length of stay&#44; which was more than one day shorter in the DOAC group&#46; This finding is probably due to the fact that the maximum anticoagulant effect of warfarin is only achieved 3-5 days after the first dose&#44; and dosage needs to be adjusted according to the international normalized ratio &#40;INR&#41; before the patient is discharged&#46; With the DOAC treatment strategy&#44; after the patient is stabilized in terms of heart failure&#44; oxygen saturation and pain &#40;which frequently occurs before the target INR is achieved&#41;&#44; there is no need to prolong hospitalization&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Among study limitations&#44; we highlight the study&#39;s retrospective design and the use of a historical cohort of patients treated with VKAs&#44; the small number of patients enrolled&#44; related to the early experience using DOACS in treating PE&#44; and the absence of thrombotic or bleeding events&#44; a fact that reflects the very good prognosis of correctly treated PE&#44; even those of intermediate-high risk&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclusions</span><p id="par0095" class="elsevierStylePara elsevierViewall">The adoption of a DOAC treatment strategy in intermediate-high risk PE patients in this typical real-world cohort was associated with comparable efficacy and safety to the conventional treatment regimen of parenteral anticoagulant plus warfarin&#46; Importantly&#44; length of stay was significantly reduced&#46; No differences were found regarding right ventricular function markers at discharge&#46; Further studies in larger cohorts will help to clarify the use of DOACs in this challenging PE population&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Ethical disclosures</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Protection of human and animal subjects</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association &#40;Declaration of Helsinki&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Confidentiality of data</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Right to privacy and informed consent</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflict of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">R&#46;B&#46; has received speaker fees from BMS&#47;Pfizer&#44; Bayer and Daiichi-Sankyo&#44; investigator fees from Bayer and personal fees &#40;advisory board&#41; from BMS&#47;Pfizer and Bayer&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">S&#46;M&#46; has received speaker fees from BMS&#47;Pfizer and Bayer&#44; investigator fees from Bayer and personal fees &#40;advisory board&#41; from Bayer&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">P&#46;M&#46; has received speaker fees from BMS&#47;Pfizer&#44; Bayer&#44; Daiichi-Sankyo and Boheringer-Ingelheim&#44; investigator fees from Bayer&#44; Boheringer-Ingelheim and Daiichi-Sankyo and personal fees &#40;advisory board&#41; from BMS&#47;Pfizer&#44; Boehringer Ingelheim and Daiichi-Sankyo&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Intermediate-high risk pulmonary embolism &#40;IHR-PE&#41; has a poor prognosis&#44; but is under-represented in trials of direct oral anticoagulants &#40;DOACs&#41; in venous thromboembolic disease &#40;VTE&#41;&#46; We aimed to assess whether the administration of DOACs was equivalent to the conventional &#40;CONV&#41; treatment of low-molecular weight heparin bridged with warfarin for treating IHR-PE&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We conducted a retrospective cohort study including 59 consecutive patients admitted with IHR-PE and followed for up to three months after discharge&#46; Two groups were created based on the anticoagulant strategy&#58; CONV &#40;n&#61;35&#41; and DOAC &#40;n&#61;24&#41;&#46; The efficacy endpoints were death&#44; recurrent PE&#44; estimated pulmonary artery systolic pressure &#40;PASP&#41;&#44; right ventricular systolic function &#40;RVSF&#41; at discharge&#44; and length of stay&#59; the safety endpoint was major bleeding&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The two groups were similar regarding demographics&#44; PE etiology and markers of clinical severity&#46; There were four in-hospital deaths in the CONV group and none in the DOAC group&#46; No recurrent PE or major bleeding event was recorded in either group&#46; At discharge&#44; neither PASP nor RVSF was different between the groups&#46; Patients in the DOAC group were discharged 1&#46;7 days earlier on average than patients in the CONV group &#40;4&#46;7&#177;2&#46;4 vs&#46; 3&#46;0&#177;1&#46;5 days&#44; p&#61;0&#46;002&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The adoption of a DOAC treatment strategy in this real-world cohort of IHR-PE patients was associated with similar efficacy and safety to the CONV approach&#46; The fact that monitoring of anticoagulation effect was unnecessary probably led to the significant reduction in length of stay&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "pt" => array:3 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introdu&#231;&#227;o</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">O tromboembolismo pulmonar de risco interm&#233;dio-elevado &#40;TEP-IE&#41; condiciona um progn&#243;stico mais agravado&#44; mas se encontra sub-representado nos ensaios dos anticoagulantes orais diretos &#40;ACOd&#41; na doen&#231;a tromboemb&#243;lica venosa &#40;DTV&#41;&#46; Avaliamos se a administra&#231;&#227;o de ACOd foi equivalente &#224; estrat&#233;gia terap&#234;utica convencional &#40;CONV&#41; &#40;heparina de baixo peso molecular &#40;HBPM&#41; &#43; varfarina&#41; no tratamento do TEP-IE&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Fez-se um estudo de coorte retrospetivo com 59 doentes consecutivos internados por TEP-IE&#44; seguidos at&#233; tr&#234;s meses ap&#243;s a alta&#46; Criaram-se dois grupos&#44; baseados na estrat&#233;gia terap&#234;utica anticoagulante&#58; CONV &#40;n &#61; 35&#41; e DOAC &#40;n &#61; 24&#41; &#40;ACOd&#41;&#46; Os desfechos de efic&#225;cia foram a morte&#44; o TEP recorrente&#44; a press&#227;o sist&#243;lica na art&#233;ria pulmonar &#40;PSAP&#41;&#44; a fun&#231;&#227;o ventricular direita &#40;FVD&#41; e a dura&#231;&#227;o do internamento&#59; o desfecho de seguran&#231;a foi a hemorragia <span class="elsevierStyleItalic">major</span>&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Os grupos eram compar&#225;veis relativamente aos aspetos demogr&#225;ficos&#44; &#224; etiologia do TEP e aos marcadores de gravidade cl&#237;nica&#46; Ocorreram quatro mortes intra-hospitalares no grupo CONV e nenhuma no grupo DOAC&#46; Nenhum evento de TEP recorrente ou hemorragia <span class="elsevierStyleItalic">major</span> ocorreu em qualquer dos grupos&#46; &#192; data de alta&#44; quer a PSAP quer a FVD n&#227;o diferiram entre os dois grupos&#46; A alta ocorreu 1&#44;7 dia mais cedo no grupo DOAC do que no grupo CONV &#40;4&#44;7&#177;2&#44;4 <span class="elsevierStyleItalic">versus</span> 3&#44;0&#177;1&#44;5 dias&#44; p &#61; 0&#44;002&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A ado&#231;&#227;o de uma estrat&#233;gia de tratamento com ACOd associou-se a um perfil de efic&#225;cia e seguran&#231;a semelhante &#224; abordagem convencional&#46; A aus&#234;ncia da necessidade de monitora&#231;&#227;o do efeito anticoagulante provavelmente motivou a redu&#231;&#227;o na dura&#231;&#227;o de internamento&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introdu&#231;&#227;o"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclus&#245;es"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:3 [
        "etiqueta" => "1"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Both authors contributed equally to this work</p>"
        "identificador" => "fn1"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1064
            "Ancho" => 1250
            "Tamanyo" => 102637
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Study population flowchart&#46; CONV&#58; conventional anticoagulation&#59; DOAC&#58; direct oral anticoagulant&#59; PE&#58; pulmonary embolism&#46;</p>"
        ]
      ]
      1 => 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:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">BNP&#58; B-type natriuretic peptide&#59; CK&#58; creatine kinase&#59; CONV&#58; conventional anticoagulation group&#59; CrCl&#58; creatinine clearance&#59; CTPA&#58; computed tomography pulmonary angiography&#59; DOAC&#58; direct oral anticoagulant group&#59; PE&#58; pulmonary embolism&#59; TnI&#58; troponin I&#59; VTE&#58; venous thromboembolism&#46;</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">Variable&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">CONV &#40;n&#61;35&#41;&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">DOAC &#40;n&#61;24&#41;&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">p&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age&#44; years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62&#177;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61&#177;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;770&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">Male&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13 &#40;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9 &#40;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">--&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="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">CrCl&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#60;30 ml&#47;min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 &#40;2&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0 &#40;0&#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"><span class="elsevierStyleHsp" style=""></span>30 to &#60;50 ml&#47;min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;14&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;881&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"><span class="elsevierStyleHsp" style=""></span>50 to &#60;80 ml&#47;min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;28&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;41&#46;7&#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"><span class="elsevierStyleHsp" style=""></span>&#8805;80 ml&#47;min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19 &#40;54&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12 &#40;50&#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" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Diagnostic method and classification</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CTPA&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">--&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="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Laboratory tests</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>D-dimers&#44; &#956;g&#47;ml &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;93 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;44 &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;897&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"><span class="elsevierStyleHsp" style=""></span>BNP&#44; pg&#47;ml &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">420&#46;17 &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">163&#46;46 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;095&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"><span class="elsevierStyleHsp" style=""></span>TnI&#44; ng&#47;ml &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;75 &#40;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;57 &#40;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;717&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"><span class="elsevierStyleHsp" style=""></span>Myoglobin&#44; ng&#47;ml &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">116&#46;09 &#40;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">53&#46;79 &#40;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;138&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"><span class="elsevierStyleHsp" style=""></span>CK&#44; U&#47;L &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">128&#46;73 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90&#46;88 &#40;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;337&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"><span class="elsevierStyleHsp" style=""></span>CK-MB&#44; U&#47;L &#40;n&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;45 &#40;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;73 &#40;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;778&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="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">PE risk factors&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Unprovoked&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17 &#40;49&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21 &#40;87&#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"><span class="elsevierStyleHsp" style=""></span>Provoked&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11 &#40;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;030&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"><span class="elsevierStyleHsp" style=""></span>Not reported&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&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"><span class="elsevierStyleHsp" style=""></span>Previous VTE&#44; n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">--&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">--&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">--&nbsp;\t\t\t\t\t\t\n
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      "titulo" => "References"
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        0 => array:2 [
          "identificador" => "bibs0015"
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                  "referenciaCompleta" => "Silverstein MD&#44; Heit JA&#44; Mohr DN&#44; et al&#46; Trends in the incidence of deep vein thrombosis and pulmonary embolism&#58; a 25-year population-based study&#46; Arch Intern Med&#46; 1998&#59; 158&#40;6&#41;&#58;585-593&#46;http&#58;&#47;&#47;www&#46;ncbi&#46;nlm&#46;nih&#46;gov&#47;pubmed&#47;9521222&#46; Accessed June 29&#44; 2016&#46;"
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                      "titulo" => "Antithrombotic therapy for VTE disease&#58; Antithrombotic Therapy and Prevention of Thrombosis&#44; 9<span class="elsevierStyleSup">th</span> ed&#58; American College of Chest Physicians Evidence-Based Clinical Practice Guidelines"
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Article information

ISSN: 21742049
Original language: English

DOI:10.1016/j.repce.2017.11.003

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Year/Month	Html	Pdf	Total

2024 November	5	2	7
2024 October	49	22	71
2024 September	49	23	72
2024 August	49	31	80
2024 July	39	31	70
2024 June	29	19	48
2024 May	44	21	65
2024 April	34	20	54
2024 March	37	21	58
2024 February	36	19	55
2024 January	31	22	53
2023 December	24	20	44
2023 November	34	21	55
2023 October	24	16	40
2023 September	14	18	32
2023 August	29	12	41
2023 July	22	8	30
2023 June	24	9	33
2023 May	42	21	63
2023 April	23	6	29
2023 March	63	21	84
2023 February	37	18	55
2023 January	34	21	55
2022 December	41	24	65
2022 November	59	29	88
2022 October	48	28	76
2022 September	47	39	86
2022 August	50	31	81
2022 July	41	45	86
2022 June	43	30	73
2022 May	38	33	71
2022 April	41	31	72
2022 March	46	47	93
2022 February	37	41	78
2022 January	32	18	50
2021 December	27	39	66
2021 November	33	44	77
2021 October	39	44	83
2021 September	27	28	55
2021 August	39	29	68
2021 July	19	18	37
2021 June	22	25	47
2021 May	36	32	68
2021 April	54	20	74
2021 March	42	22	64
2021 February	41	24	65
2021 January	19	21	40
2020 December	34	22	56
2020 November	24	8	32
2020 October	27	9	36
2020 September	54	27	81
2020 August	9	8	17
2020 July	24	13	37
2020 June	27	12	39
2020 May	30	5	35
2020 April	36	14	50
2020 March	36	6	42
2020 February	63	16	79
2020 January	29	8	37
2019 December	23	3	26
2019 November	29	10	39
2019 October	33	7	40
2019 September	15	10	25
2019 August	25	11	36
2019 July	28	4	32
2019 June	23	17	40
2019 May	37	16	53
2019 April	21	15	36
2019 March	67	10	77
2019 February	36	4	40
2019 January	67	6	73
2018 December	36	13	49
2018 November	52	15	67
2018 October	94	11	105
2018 September	22	10	32
2018 August	31	6	37
2018 July	13	2	15
2018 June	27	10	37
2018 May	33	5	38
2018 April	31	5	36
2018 March	36	4	40
2018 February	24	5	29
2018 January	33	10	43
2017 December	16	10	26

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