Editorial
The role of the new oral anticoagulants in the treatment of coronary disease
Papel de los nuevos anticoagulantes orales en el tratamiento de la enfermedad coronaria
Hernando del Portilloa, Juan J. Badimónb, Jaime R. Cabralesa, Darío Echeverria,
Corresponding author
a Department of Hemodynamics and Cardiovascular Interventionism, Fundación CardioInfantil – Instituto de Cardiología – Department of Medicine, Universidad del Rosario, Bogotá, Colombia
b Atherothrombosis Research Unit, The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, United States
Read
5773
Timeswas read the article
1121
Total PDF
4652
Total HTML
Share statistics
array:24 [ "pii" => "S0120563316301887" "issn" => "01205633" "doi" => "10.1016/j.rccar.2016.10.033" "estado" => "S300" "fechaPublicacion" => "2016-11-01" "aid" => "346" "copyrightAnyo" => "2016" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "sco" "cita" => "Rev Col Cardiol. 2016;23:e13-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1720 "formatos" => array:3 [ "EPUB" => 44 "HTML" => 1133 "PDF" => 543 ] ] "itemSiguiente" => array:19 [ "pii" => "S0120563316301905" "issn" => "01205633" "doi" => "10.1016/j.rccar.2016.09.008" "estado" => "S300" "fechaPublicacion" => "2016-11-01" "aid" => "348" "copyright" => "Sociedad Colombiana de Cardiología y Cirugía Cardiovascular" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "sco" "cita" => "Rev Col Cardiol. 2016;23:464-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1456 "formatos" => array:3 [ "EPUB" => 44 "HTML" => 1103 "PDF" => 309 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "El papel del cardiólogo clínico en un programa de prevención cardiovascular" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "464" "paginaFinal" => "466" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "The role of the clinical cardiologist in a cardiovascular prevention program" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Nicolás Jaramillo Gómez" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Nicolás" "apellidos" => "Jaramillo Gómez" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0120563316301905?idApp=UINPBA00004N" "url" => "/01205633/0000002300000006/v1_201612070101/S0120563316301905/v1_201612070101/es/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0120563316301875" "issn" => "01205633" "doi" => "10.1016/j.rccar.2016.10.032" "estado" => "S300" "fechaPublicacion" => "2016-11-01" "aid" => "345" "copyright" => "Sociedad Colombiana de Cardiología y Cirugía Cardiovascular" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "sco" "cita" => "Rev Col Cardiol. 2016;23:461-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2024 "formatos" => array:3 [ "EPUB" => 45 "HTML" => 1405 "PDF" => 574 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Papel de los nuevos anticoagulantes orales en el tratamiento de la enfermedad coronaria" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "461" "paginaFinal" => "463" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "The role of the new oral anticoagulants in the treatment of coronary disease" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Hernando del Portillo, Juan J. Badimón, Jaime R. Cabrales, Darío Echeverri" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Hernando" "apellidos" => "del Portillo" ] 1 => array:2 [ "nombre" => "Juan J." "apellidos" => "Badimón" ] 2 => array:2 [ "nombre" => "Jaime R." "apellidos" => "Cabrales" ] 3 => array:2 [ "nombre" => "Darío" "apellidos" => "Echeverri" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0120563316301875?idApp=UINPBA00004N" "url" => "/01205633/0000002300000006/v1_201612070101/S0120563316301875/v1_201612070101/es/main.assets" ] "asociados" => array:1 [ 0 => array:19 [ "pii" => "S0120563316301875" "issn" => "01205633" "doi" => "10.1016/j.rccar.2016.10.032" "estado" => "S300" "fechaPublicacion" => "2016-11-01" "aid" => "345" "copyright" => "Sociedad Colombiana de Cardiología y Cirugía Cardiovascular" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "sco" "cita" => "Rev Col Cardiol. 2016;23:461-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2024 "formatos" => array:3 [ "EPUB" => 45 "HTML" => 1405 "PDF" => 574 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Papel de los nuevos anticoagulantes orales en el tratamiento de la enfermedad coronaria" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "461" "paginaFinal" => "463" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "The role of the new oral anticoagulants in the treatment of coronary disease" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Hernando del Portillo, Juan J. Badimón, Jaime R. Cabrales, Darío Echeverri" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Hernando" "apellidos" => "del Portillo" ] 1 => array:2 [ "nombre" => "Juan J." "apellidos" => "Badimón" ] 2 => array:2 [ "nombre" => "Jaime R." "apellidos" => "Cabrales" ] 3 => array:2 [ "nombre" => "Darío" "apellidos" => "Echeverri" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0120563316301875?idApp=UINPBA00004N" "url" => "/01205633/0000002300000006/v1_201612070101/S0120563316301875/v1_201612070101/es/main.assets" ] ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "The role of the new oral anticoagulants in the treatment of coronary disease" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "e13" "paginaFinal" => "e15" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Hernando del Portillo, Juan J. Badimón, Jaime R. Cabrales, Darío Echeverri" "autores" => array:4 [ 0 => array:3 [ "nombre" => "Hernando" "apellidos" => "del Portillo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Juan J." "apellidos" => "Badimón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Jaime R." "apellidos" => "Cabrales" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:4 [ "nombre" => "Darío" "apellidos" => "Echeverri" "email" => array:1 [ 0 => "decheverri@cardioinfantil.org" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Hemodynamics and Cardiovascular Interventionism, Fundación CardioInfantil – Instituto de Cardiología – Department of Medicine, Universidad del Rosario, Bogotá, Colombia" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Atherothrombosis Research Unit, The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, United States" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Papel de los nuevos anticoagulantes orales en el tratamiento de la enfermedad coronaria" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The new oral anticoagulants are here to stay in the prevention of ischemic cerebrovascular accidents in patients with nonvalvular atrial fibrillation. Several clinical studies have established their efficacy and safety<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1–3</span></a>. However, the role these new oral anticoagulants might have in other pathologies, such as coronary disease, has not been well studied and there are still several important questions which have not been answered. One of these questions is the role the new oral anticoagulants could have in the secondary prevention of coronary disease, given that in spite of optimal medical treatment and dual anti-platelet therapy, the risk of reinfarction has only decreased 30%. This phenomenon may possibly be explained by other related factors, such as lipid metabolism, the inflammatory state, and the prothrombotic state, in which the activated X factor (Xa), plays a fundamental role by triggering the conversion of inactive prothrombin into thrombin, which is the strongest agonist for platelet aggregation<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">4,5</span></a>. The second question is related to those patients with nonvalvular atrial fibrillation and coronary disease who require stent implantation, in whom the new oral anticoagulants could be an alternative in combination with antiplatelet medications.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Currently in Colombia, there are two types of new oral anticoagulants available: direct inhibitors of activated factor X (rivaroxaban and apixaban) and direct thrombin inhibitors (dabigatran), which may be new therapeutic tools to answer these questions. Factor Xa inhibitors indirectly suppress the <span class="elsevierStyleItalic">synthesis</span> of thrombin by inhibiting this factor, while the direct antithrombin agents inhibit the <span class="elsevierStyleItalic">activity</span> of thrombin.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">First scenario: secondary prevention in coronary disease</span><p id="par0015" class="elsevierStylePara elsevierViewall">Coronary thrombosis depends on platelet activity and its integration with the coagulation pathways, where the vitamin K-dependent factors (II,VII, IX, and X) play a very important role<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a>; this is why vitamin K antagonists (VKA) were studied a few years ago for secondary prevention of cardiovascular events, significantly reducing episodes of cerebrovascular accidents and myocardial infarction. The enormous benefits of this class of agents had an enormous disadvantage, which was the significant increase in bleeding<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a>. This increase is probably associated with the difficulty in achieving and maintaining INR levels within therapeutic range, due to multiple interactions with other medications and even with foods, as well as a slow onset of action. All these conditioning factors are part of the reason why VKA are not currently considered first choice medications for the prevention and treatment of cardiovascular events.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Recent studies have evaluated the therapeutic potential of the new oral anticoagulants for secondary prevention in patients with coronary disease. The most important studies are APPRAISE-2 with apixaban<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a>, and the ATLAS-ACS 2 TIMI 51 with rivaroxaban<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a>, whose primary objective was to decrease cardiovascular death, myocardial infarction, and CVA in patients with known coronary disease. Unfortunately, the results were not very encouraging. APPRAISE-2 was prematurely terminated due to excessive bleeding. The ATLAS-ACS 2 TIMI 51 study was positive, but the results are hard to explain from a pharmacological point of view, since the low doses of rivaroxaban at 2.5<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>hours decreased cardiovascular mortality, but not myocardial infarction (which is the principal cause of cardiovascular death); while the 5<span class="elsevierStyleHsp" style=""></span>mg dose every 12<span class="elsevierStyleHsp" style=""></span>hours reduced the rate of myocardial infarction but not cardiovascular mortality. In addition, both doses showed increased bleeding compared with the reference control group.</p><p id="par0025" class="elsevierStylePara elsevierViewall">However, the idea that stands out to us, and which we consider important to highlight, is in the field of secondary prevention, since the benefit was mainly conferred by the results attained after the first year of treatment, the point at which most patients discontinue dual antiplatelet therapy. This is why we ask ourselves, ¿Will rivaroxaban be the next medication of choice for secondary prevention in coronary disease? In an effort to answer this question, the GEMINI-ACS-1 phase II study<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> is currently underway, which will use rivaroxaban doses of 2.5<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>hours in place of acetylsalicylic acid combined with clopidogrel and ticagrelor, seeking a double mechanism of action, and whose principle objective will be to evaluate safety in terms of bleeding, measured using the TIMI scale.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Second scenario: Triple therapy with new oral anticoagulants</span><p id="par0030" class="elsevierStylePara elsevierViewall">With the changes in the population pyramid which entail an increased patient age, as well as the increased incidence of atrial fibrillation and clear benefit of anticoagulation with new oral anticoagulants in patients with atrial fibrillation, it is increasingly more common for patients to require dual antiplatelet therapy and anticoagulation. With regard to triple therapy in patients with atrial fibrillation and coronary disease plus percutaneous coronary intervention (PCI), there are currently several ongoing studies using different types and doses of new oral anticoagulants, such as RE-DUAL PCI with dabigatran, PIONEER-atrial fibrillation with rivaroxaban, and AUGUSTUS with apixaban<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a>, which will evaluate the combination of these new oral anticoagulants with the various P<span class="elsevierStyleInf">2</span>Y<span class="elsevierStyleInf">12</span> receptor inhibitors. These studies are quite logical if three aspects are considered: 1) the greatest benefit of new oral anticoagulants versus VKA is a lower risk of bleeding; 2) some new oral anticoagulants have already been studied for secondary prevention; and 3) the new oral anticoagulants already have antidotes, some in phase III of research.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">New and possible scenarios of new oral anticoagulants in coronary disease</span><p id="par0035" class="elsevierStylePara elsevierViewall">In cases of ischemic heart failure and a reduced ejection fraction, a phase three study, COMMANDER-HF<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a>, is in progress, which is based on the theory of thrombin as the critical element for worsening heart failure. Consequently, rivaroxaban 2.5<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>hours plus dual or single antiplatelet therapy will evaluate the outcome consisting of mortality due to any cause, myocardial infarction and cerebrovascular accident. In this same context, but in the presence of left ventricular thrombi, cases have already been reported using new oral anticoagulants with complete resolution of the thrombus during echocardiographic follow-up<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a>.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Finally, in coronary ectasia, slow coronary flow, endothelial lesions and a pro-inflammatory state have been shown, which create a hypercoagulability environment<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a>. Thus, as they fulfill the still accepted characteristics of Virchow¿s triad, these patients would have a high predisposition for thrombus formation and the recurrence of myocardial ischemic events. In this coronary ectasia with slow flow and coronary thrombosis, different treatment strategies have been used, such as manual thrombectomy plus anticoagulation, intracoronary thrombolytics, acetylsalicylic acid plus warfarin, glycoprotein II<span class="elsevierStyleInf">b</span>/III<span class="elsevierStyleInf">a</span> inhibitors, and drug eluting stents, yielding controversial results<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a>. In light of this, a dose of rivaroxaban of 2.5<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>hours could be an interesting and viable pharmacological option for this group of patients, since there is as yet no known specific treatment for the management of this pathology. The use of new oral anticoagulants in this context could be a new field to explore in clinical research.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "First scenario: secondary prevention in coronary disease" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Second scenario: Triple therapy with new oral anticoagulants" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "New and possible scenarios of new oral anticoagulants in coronary disease" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-09-30" "fechaAceptado" => "2016-10-06" "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rivaroxaban versus warfarin in nonvalvular atrial fibrillation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.R. Patel" 1 => "K.W. Mahaffey" 2 => "J. Garg" 3 => "G. Pan" 4 => "D.E. Singer" 5 => "W. Hacke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1009638" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "2011" "volumen" => "365" "paginaInicial" => "883" "paginaFinal" => "891" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21830957" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0085" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Apixaban versus warfarin in patients with atrial fibrillation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.B. Granger" 1 => "J.H. Alexander" 2 => "J.J.V. McMurray" 3 => "R.D. Lopes" 4 => "E.M. Hylek" 5 => "M. Hanna" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1107039" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "2011" "volumen" => "365" "paginaInicial" => "981" "paginaFinal" => "992" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21870978" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0090" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dabigatran versus warfarin in patients with atrial fibrillation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.J. Connolly" 1 => "M.D. Ezekowitz" 2 => "S. Yusuf" 3 => "J. Eikelboom" 4 => "J. Oldgren" 5 => "A. Parekh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0905561" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "2009" "volumen" => "361" "paginaInicial" => "1139" "paginaFinal" => "1151" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19717844" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0095" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Perspectives: The burden of cardiovascular risk factors and coronary heart disease in Europe and worldwide" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G. Vilahur" 1 => "J.J. Badimon" 2 => "R. Bugiardini" 3 => "L. Badimon" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Eur Heart J." "fecha" => "2014" "volumen" => "16" "numero" => "suppl A" "paginaInicial" => "A7" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0100" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Perspectives: Direct and specific inhibition of factor Xa: an emerging therapeutic strategy for atherothrombotic disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.G. Santos-Gallego" 1 => "L. Badimon" 2 => "J.J. Badimón" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Eur Heart J." "fecha" => "2014" "volumen" => "16" "numero" => "suppl A" "paginaInicial" => "A56" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0105" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oral anticoagulants in coronary heart disease (Section IV). Position paper of the ESC Working Group on Thrombosis-Task Force on Anticoagulants in Heart Disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. De Caterina" 1 => "S. Husted" 2 => "L. Wallentin" 3 => "F. Andreotti" 4 => "H. Arnesen" 5 => "F. Bachmann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1160/TH15-09-0703" "Revista" => array:6 [ "tituloSerie" => "Thromb Haemost." "fecha" => "2016" "volumen" => "115" "paginaInicial" => "685" "paginaFinal" => "711" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26952877" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0110" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Warfarin, aspirin, or both after myocardial infarction" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Hurlen" 1 => "M. Abdelnoor" 2 => "P. Smith" 3 => "J. Erikssen" 4 => "H. Arnesen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa020496" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "2002" "volumen" => "347" "paginaInicial" => "969" "paginaFinal" => "974" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12324552" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0115" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Apixaban with antiplatelet therapy after acute coronary syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.H. Alexander" 1 => "R.D. Lopes" 2 => "S. James" 3 => "R. Kilaru" 4 => "Y. He" 5 => "P. Mohan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1105819" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "2011" "volumen" => "365" "paginaInicial" => "699" "paginaFinal" => "708" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21780946" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0120" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rivaroxaban in patients with a recent acute coronary syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.L. Mega" 1 => "E. Braunwald" 2 => "S.D. Wiviott" 3 => "J.-P. Bassand" 4 => "D.L. Bhatt" 5 => "C. Bode" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1112277" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "2012" "volumen" => "366" "paginaInicial" => "9" "paginaFinal" => "19" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22077192" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0125" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A randomized trial to compare the safety of rivaroxaban vs aspirin in addition to either clopidogrel or ticagrelor in acute coronary syndrome: The design of the GEMINI-ACS-1 phase II study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.J. Povsic" 1 => "M.T. Roe" 2 => "E.M. Ohman" 3 => "P.G. Steg" 4 => "S. James" 5 => "A. Plotnikov" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ahj.2016.01.004" "Revista" => array:6 [ "tituloSerie" => "Am Heart J." "fecha" => "2016" "volumen" => "174" "paginaInicial" => "120" "paginaFinal" => "128" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26995378" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0130" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Heidbuchel" 1 => "P. Verhamme" 2 => "M. Alings" 3 => "M. Antz" 4 => "H.-C. Diener" 5 => "W. Hacke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/europace/euv309" "Revista" => array:6 [ "tituloSerie" => "Europace." "fecha" => "2015" "volumen" => "17" "paginaInicial" => "1467" "paginaFinal" => "1507" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26324838" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0135" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rationale and design of a randomized, double-blind, event-driven, multicentre study comparing the efficacy and safety of oral rivaroxaban with placebo for reducing the risk of death, myocardial infarction or stroke in subjects with heart failure and significant coronary artery disease following an exacerbation of heart failure: the COMMANDER HF trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Zannad" 1 => "B. Greenberg" 2 => "J.G.F. Cleland" 3 => "M. Gheorghiade" 4 => "D.J. van Veldhuisen" 5 => "M.R. Mehra" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ejhf.266" "Revista" => array:6 [ "tituloSerie" => "Eur J Heart Fail." "fecha" => "2015" "volumen" => "17" "paginaInicial" => "735" "paginaFinal" => "742" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25919061" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0140" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful resolution of a left ventricular thrombus with apixaban treatment following acute myocardial infarction" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Y. Mano" 1 => "K. Koide" 2 => "H. Sukegawa" 3 => "M. Kodaira" 4 => "T. Ohki" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00380-014-0562-z" "Revista" => array:6 [ "tituloSerie" => "Heart Vessels." "fecha" => "2016" "volumen" => "31" "paginaInicial" => "118" "paginaFinal" => "123" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25081096" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0145" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Coronary artery ectasia is related to coronary slow flow and inflammatory activation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N.D. Brunetti" 1 => "G. Salvemini" 2 => "A. Cuculo" 3 => "A. Ruggiero" 4 => "L. De Gennaro" 5 => "A. Gaglione" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.atherosclerosis.2014.01.018" "Revista" => array:6 [ "tituloSerie" => "Atherosclerosis." "fecha" => "2014" "volumen" => "233" "paginaInicial" => "636" "paginaFinal" => "640" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24553454" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0150" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Coronary artery ectasia: new insights into pathophysiology, diagnosis, and treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Eitan" 1 => "A. Roguin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MCA.0000000000000379" "Revista" => array:6 [ "tituloSerie" => "Coron Artery Dis." "fecha" => "2016" "volumen" => "27" "paginaInicial" => "420" "paginaFinal" => "428" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27218145" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/01205633/0000002300000006/v1_201612070101/S0120563316301887/v1_201612070101/en/main.assets" "Apartado" => array:4 [ "identificador" => "42423" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Editoriales" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/01205633/0000002300000006/v1_201612070101/S0120563316301887/v1_201612070101/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0120563316301887?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 33 | 0 | 33 |
| 2024 September | 62 | 6 | 68 |
| 2024 August | 48 | 1 | 49 |
| 2024 July | 66 | 3 | 69 |
| 2024 June | 70 | 2 | 72 |
| 2024 May | 46 | 2 | 48 |
| 2024 April | 69 | 4 | 73 |
| 2024 March | 51 | 9 | 60 |
| 2024 February | 35 | 4 | 39 |
| 2024 January | 71 | 10 | 81 |
| 2023 December | 73 | 9 | 82 |
| 2023 November | 75 | 8 | 83 |
| 2023 October | 83 | 7 | 90 |
| 2023 September | 50 | 8 | 58 |
| 2023 August | 38 | 5 | 43 |
| 2023 July | 63 | 14 | 77 |
| 2023 June | 46 | 4 | 50 |
| 2023 May | 68 | 5 | 73 |
| 2023 April | 51 | 0 | 51 |
| 2023 March | 51 | 12 | 63 |
| 2023 February | 50 | 4 | 54 |
| 2023 January | 70 | 9 | 79 |
| 2022 December | 40 | 9 | 49 |
| 2022 November | 54 | 9 | 63 |
| 2022 October | 55 | 13 | 68 |
| 2022 September | 59 | 14 | 73 |
| 2022 August | 41 | 14 | 55 |
| 2022 July | 52 | 12 | 64 |
| 2022 June | 48 | 11 | 59 |
| 2022 May | 62 | 7 | 69 |
| 2022 April | 48 | 4 | 52 |
| 2022 March | 79 | 14 | 93 |
| 2022 February | 82 | 23 | 105 |
| 2022 January | 92 | 28 | 120 |
| 2021 December | 47 | 15 | 62 |
| 2021 November | 50 | 10 | 60 |
| 2021 October | 65 | 17 | 82 |
| 2021 September | 37 | 14 | 51 |
| 2021 August | 54 | 11 | 65 |
| 2021 July | 52 | 12 | 64 |
| 2021 June | 64 | 19 | 83 |
| 2021 May | 56 | 15 | 71 |
| 2021 April | 192 | 9 | 201 |
| 2021 March | 68 | 8 | 76 |
| 2021 February | 57 | 9 | 66 |
| 2021 January | 69 | 19 | 88 |
| 2020 December | 76 | 4 | 80 |
| 2020 November | 67 | 9 | 76 |
| 2020 October | 60 | 18 | 78 |
| 2020 September | 69 | 21 | 90 |
| 2020 August | 63 | 15 | 78 |
| 2020 July | 78 | 19 | 97 |
| 2020 June | 67 | 11 | 78 |
| 2020 May | 55 | 18 | 73 |
| 2020 April | 71 | 10 | 81 |
| 2020 March | 86 | 10 | 96 |
| 2020 February | 90 | 13 | 103 |
| 2020 January | 74 | 11 | 85 |
| 2019 December | 78 | 18 | 96 |
| 2019 November | 55 | 13 | 68 |
| 2019 October | 60 | 19 | 79 |
| 2019 September | 46 | 8 | 54 |
| 2019 August | 52 | 26 | 78 |
| 2019 July | 62 | 9 | 71 |
| 2019 June | 64 | 45 | 109 |
| 2019 May | 83 | 57 | 140 |
| 2019 April | 72 | 11 | 83 |
| 2019 March | 39 | 9 | 48 |
| 2019 February | 38 | 11 | 49 |
| 2019 January | 19 | 9 | 28 |
| 2018 December | 23 | 7 | 30 |
| 2018 November | 26 | 5 | 31 |
| 2018 October | 20 | 13 | 33 |
| 2018 September | 9 | 2 | 11 |
| 2018 August | 8 | 9 | 17 |
| 2018 July | 9 | 8 | 17 |
| 2018 June | 9 | 4 | 13 |
| 2018 May | 16 | 4 | 20 |
| 2018 April | 16 | 6 | 22 |
| 2018 March | 8 | 4 | 12 |
| 2018 February | 7 | 1 | 8 |
| 2018 January | 5 | 5 | 10 |
| 2017 December | 10 | 5 | 15 |
| 2017 November | 6 | 2 | 8 |
| 2017 October | 7 | 5 | 12 |
| 2017 September | 4 | 9 | 13 |
| 2017 August | 7 | 7 | 14 |
| 2017 July | 12 | 11 | 23 |
| 2017 June | 11 | 36 | 47 |
| 2017 May | 27 | 39 | 66 |
| 2017 April | 13 | 16 | 29 |
| 2017 March | 16 | 46 | 62 |
| 2017 February | 23 | 8 | 31 |
| 2017 January | 16 | 10 | 26 |
| 2016 December | 27 | 18 | 45 |
| 2016 November | 1 | 5 | 6 |
Show all