array:24 [
  "pii" => "S0300289618301546"
  "issn" => "03002896"
  "doi" => "10.1016/j.arbres.2018.03.010"
  "estado" => "S300"
  "fechaPublicacion" => "2019-02-01"
  "aid" => "1880"
  "copyright" => "SEPAR"
  "copyrightAnyo" => "2018"
  "documento" => "simple-article"
  "crossmark" => 1
  "subdocumento" => "crp"
  "cita" => "Arch Bronconeumol. 2019;55:102-3"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 527
    "formatos" => array:3 [
      "EPUB" => 57
      "HTML" => 326
      "PDF" => 144
    ]
  ]
  "Traduccion" => array:1 [
    "en" => array:19 [
      "pii" => "S1579212919300059"
      "issn" => "15792129"
      "doi" => "10.1016/j.arbr.2018.03.015"
      "estado" => "S300"
      "fechaPublicacion" => "2019-02-01"
      "aid" => "1880"
      "copyright" => "SEPAR"
      "documento" => "simple-article"
      "crossmark" => 1
      "subdocumento" => "crp"
      "cita" => "Arch Bronconeumol. 2019;55:102-3"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:2 [
        "total" => 336
        "formatos" => array:3 [
          "EPUB" => 60
          "HTML" => 192
          "PDF" => 84
        ]
      ]
      "en" => array:10 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>"
        "titulo" => "Living With Severe Pulmonary Arterial Hypertension Without an Infusion Pump&#63; Selexipag has a Role to Play"
        "tienePdf" => "en"
        "tieneTextoCompleto" => "en"
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "102"
            "paginaFinal" => "103"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "es" => array:1 [
            "titulo" => "&#191;Viviendo con hipertensi&#243;n arterial pulmonar grave sin una bomba de infusi&#243;n&#63; Selexipag tiene un papel"
          ]
        ]
        "contieneTextoCompleto" => array:1 [
          "en" => true
        ]
        "contienePdf" => array:1 [
          "en" => true
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Mar&#237;a L&#225;zaro Salvador, Finn Akerstr&#246;m, Pilar Escribano Sub&#237;as, Alejandro Berenguel Sen&#232;c&#41;n, Virgilio Martinez Mateo, Luis Rodriguez Padial"
            "autores" => array:6 [
              0 => array:2 [
                "nombre" => "Mar&#237;a"
                "apellidos" => "L&#225;zaro Salvador"
              ]
              1 => array:2 [
                "nombre" => "Finn"
                "apellidos" => "Akerstr&#246;m"
              ]
              2 => array:2 [
                "nombre" => "Pilar"
                "apellidos" => "Escribano Sub&#237;as"
              ]
              3 => array:2 [
                "nombre" => "Alejandro"
                "apellidos" => "Berenguel Sen&#232;c&#41;n"
              ]
              4 => array:2 [
                "nombre" => "Virgilio"
                "apellidos" => "Martinez Mateo"
              ]
              5 => array:2 [
                "nombre" => "Luis"
                "apellidos" => "Rodriguez Padial"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "en"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S0300289618301546"
          "doi" => "10.1016/j.arbres.2018.03.010"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => true
            "ES2" => true
            "LATM" => true
          ]
          "gratuito" => true
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289618301546?idApp=UINPBA00003Z"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212919300059?idApp=UINPBA00003Z"
      "url" => "/15792129/0000005500000002/v1_201902020656/S1579212919300059/v1_201902020656/en/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S0300289618301820"
    "issn" => "03002896"
    "doi" => "10.1016/j.arbres.2018.04.016"
    "estado" => "S300"
    "fechaPublicacion" => "2019-02-01"
    "aid" => "1908"
    "copyright" => "SEPAR"
    "documento" => "simple-article"
    "crossmark" => 1
    "subdocumento" => "crp"
    "cita" => "Arch Bronconeumol. 2019;55:104-5"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 1290
      "formatos" => array:3 [
        "EPUB" => 63
        "HTML" => 980
        "PDF" => 247
      ]
    ]
    "es" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Carta cient&#237;fica</span>"
      "titulo" => "Tuberculosis pulmonar con presentaci&#243;n at&#237;pica en paciente inmunocompetente"
      "tienePdf" => "es"
      "tieneTextoCompleto" => "es"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "104"
          "paginaFinal" => "105"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Atypical Presentation of Pulmonary Tuberculosis in an Immunocompetent Patient"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "es" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figura 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 575
              "Ancho" => 1300
              "Tamanyo" => 92230
            ]
          ]
          "descripcion" => array:1 [
            "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Radiograf&#237;a de t&#243;rax posteroanterior &#40;A&#41; con opacidades pseudonodulares parcheadas que predominan en los campos medios y superiores&#46; No se aprecia derrame pleural ni ensanchamiento mediast&#237;nico&#46; TC de t&#243;rax en corte transversal &#40;B&#41; en la que se observan opacidades pulmonares centrolobulillares con tendencia a la coalescencia&#44; de predominio en los campos superiores y medios&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Elisabeth Gallardo P&#233;rez, Cristina Trasancos Escura, Isabel Pacheco Tenza, Ignacio Massa Navarrete"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Elisabeth"
              "apellidos" => "Gallardo P&#233;rez"
            ]
            1 => array:2 [
              "nombre" => "Cristina"
              "apellidos" => "Trasancos Escura"
            ]
            2 => array:2 [
              "nombre" => "Isabel"
              "apellidos" => "Pacheco Tenza"
            ]
            3 => array:2 [
              "nombre" => "Ignacio"
              "apellidos" => "Massa Navarrete"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S157921291830421X"
        "doi" => "10.1016/j.arbr.2018.12.001"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S157921291830421X?idApp=UINPBA00003Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289618301820?idApp=UINPBA00003Z"
    "url" => "/03002896/0000005500000002/v1_201902020631/S0300289618301820/v1_201902020631/es/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S0300289618302928"
    "issn" => "03002896"
    "doi" => "10.1016/j.arbres.2018.07.003"
    "estado" => "S300"
    "fechaPublicacion" => "2019-02-01"
    "aid" => "1958"
    "copyright" => "SEPAR"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "sco"
    "cita" => "Arch Bronconeumol. 2019;55:101"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 467
      "formatos" => array:3 [
        "EPUB" => 49
        "HTML" => 279
        "PDF" => 139
      ]
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Clinical Image</span>"
      "titulo" => "A Rare Cause of Chronic Pulmonary Embolism&#58; Hydatid Cyst"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:1 [
          "paginaInicial" => "101"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Una causa infrecuente de embolismo pulmonar cr&#243;nico&#58; un quiste hidat&#237;dico"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Fig&#46; 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 750
              "Ancho" => 950
              "Tamanyo" => 62462
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Computed tomography thorax&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Hanane Asri, Adil Zegmout, Ahmed Abid"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Hanane"
              "apellidos" => "Asri"
            ]
            1 => array:2 [
              "nombre" => "Adil"
              "apellidos" => "Zegmout"
            ]
            2 => array:2 [
              "nombre" => "Ahmed"
              "apellidos" => "Abid"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S1579212919300060"
        "doi" => "10.1016/j.arbr.2018.07.016"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212919300060?idApp=UINPBA00003Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289618302928?idApp=UINPBA00003Z"
    "url" => "/03002896/0000005500000002/v1_201902020631/S0300289618302928/v1_201902020631/en/main.assets"
  ]
  "en" => array:14 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>"
    "titulo" => "Living With Severe Pulmonary Arterial Hypertension Without an Infusion Pump&#63; Selexipag has a Role to Play"
    "tieneTextoCompleto" => true
    "saludo" => "Dear Editor&#44;"
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "102"
        "paginaFinal" => "103"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Mar&#237;a L&#225;zaro Salvador, Finn Akerstr&#246;m, Pilar Escribano Sub&#237;as, Alejandro Berenguel Sen&#233;n, Virgilio Martinez Mateo, Luis Rodriguez Padial"
        "autores" => array:6 [
          0 => array:4 [
            "nombre" => "Mar&#237;a"
            "apellidos" => "L&#225;zaro Salvador"
            "email" => array:1 [
              0 => "maria&#46;lasal&#64;gmail&#46;com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Finn"
            "apellidos" => "Akerstr&#246;m"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Pilar"
            "apellidos" => "Escribano Sub&#237;as"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Alejandro"
            "apellidos" => "Berenguel Sen&#233;n"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Virgilio"
            "apellidos" => "Martinez Mateo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Luis"
            "apellidos" => "Rodriguez Padial"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Department of Cardiology&#44; Hospital Virgen de la Salud&#44; Toledo&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Department of Cardiology&#44; Hospital Universitario 12 de Octubre&#44; Madrid&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Department of Cardiology&#44; Hospital La Mancha Centro&#44; Alcazar de San Juan&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "&#191;Viviendo con hipertensi&#243;n arterial pulmonar grave sin una bomba de infusi&#243;n&#63; Selexipag tiene un papel"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pulmonary arterial hypertension &#40;PAH&#41; is a rare disease characterized by cellular proliferation and vasoconstriction of the pulmonary arterial bed&#46; PAH is a devastating disease with a high mortality despite available therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> Three well-known pathways are involved in PAH pathophysiology &#40;endothelin&#44; nitric oxide&#44; and prostacyclin&#41;&#44; which are all therapeutic targets&#46; The updated ESC&#47;ERS guidelines for the diagnosis and treatment of pulmonary hypertension recommend prostacyclin analogues in patients suffering from severe PAH&#44; referring to WHO functional class &#40;FC&#41; III and IV&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> Prostacyclin is an endogenous prostanoid&#44; that induces vasodilatation and inhibits platelet aggregation and cell proliferation&#44; and patients with PAH present decreased prostacyclin production&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> Treprostinil&#44; as prostacyclin analogue&#44; is metabolically stable&#44; long-acting&#44; and can be administered subcutaneously using a portable small delivery system&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> Although subcutaneous administration implies less risk of systemic infection or catheter dislocation&#44; subcutaneous infections and severe pain at infusion site are common and may make further treatment impossible in 7&#37;&#8211;10&#37; of the patients&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> Selexipag is a novel orally available non-prostacyclin selective prostacyclin receptor &#40;IP receptor&#41; agonist&#46; Following absorption&#44; it is hydrolyzed to an active more potent metabolite&#44; which has a 7&#46;9-h half-life&#44; allowing for twice daily dosing&#46; Common side effects &#40;all drug class related&#41; include headache&#44; diarrhea&#44; jaw pain&#44; nausea&#44; myalgia&#44; vomiting&#44; and flushings&#46; Selexipag has shown efficacy in PAH&#44; even in sequential triple combination&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> and it is currently approved for the treatment of PAH patients in WHO FC II-III&#44; both in combination with endothelin receptor antagonist &#40;ERA&#41; and&#47;or phosphodiesterase 5 inhibitors &#40;iPDE-5&#41; or in monotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> Given its oral administration&#44; selexipag avoids the complications related to continuous parenteral administration&#46; Hence&#44; switching to selexipag maybe an attractive option in patients who were once started on a parental prostacyclin&#46; However&#44; little is known with regards to the aforementioned drug switch&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> Here&#44; we present a successful case of transition from subcutaneous treprostinil to selexipag in a PAH patient reporting unbearable adverse events associated with treprostinil subcutaneous administration &#40;<a class="elsevierStyleCrossRef" href="#sec0010">Appendix A</a>&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In August 2011 a 54-year-old woman was referred to our PAH Unit due to severe idiopathic PAH with a high-risk profile according to the prognosis assessment table suggested by current guidelines<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>A&#41;&#46; After six months of combination therapy with the iPDE-5 sildenafil &#40;80<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h&#41; and the ERA ambrisentan &#40;10<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; the patient improved and achieved every low risk criteria &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>A&#41;&#46; Later on&#44; sildenafil was switched to the iPDE-5 tadalafil 40<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h due to nasal congestion&#46; Following this&#44; the patient remained stable in the low risk profile for two additional years&#46; In early 2014&#44; the patient deteriorated to the intermediate risk profile &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>A&#41; and subcutaneous treprostinil was added and titrated up to 30<span class="elsevierStyleHsp" style=""></span>ng&#47;kg&#47;min&#46; With the triple regime &#40;ERA&#160;&#43;&#160;iPDE-5&#160;&#43;&#160;treprostinil&#41;&#44; she quickly recovered her previous low-risk profile and remained stable for another 32 months&#46; Unfortunately&#44; our patient insistently complained about unbearable pain around treprostinil infusion site&#44; and several subcutaneous infections were reported&#46; Consequently&#44; we planned progressive transition from subcutaneous treprostinil to oral selexipag after non-invasive risk profile assessment &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>B&#41;&#46; Patient refused right heart catheterization&#46; Progressive treprostinil down-titration and simultaneous selexipag up-titration was performed in outpatient clinic&#44; under close supervision&#44; throughout 8 weeks&#44; so that every week&#44; 4<span class="elsevierStyleHsp" style=""></span>ng&#47;kg&#47;min of treprostinil were reduced and 200<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;12<span class="elsevierStyleHsp" style=""></span>h were added&#46; During the first 4 days of selexipag intake&#44; patient reported mild diarrhoea&#44; self-limited within the first week&#46; No other side effects were reported&#46; Patient ended up taking maximal doses of oral selexipag 1600<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; plus her previous tadalafil and ambrisentan combination therapy unvaried&#46; Six months after treprostinil withdrawal&#44; the patient risk profile had slightly improved &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>B&#41;&#46; Her functional capacity was better &#40;both in 6<span class="elsevierStyleHsp" style=""></span>min walking test distance and in cardiopulmonary exercise test&#41; and quality of life drastically increased&#59; not having to carry the infusion pump was a great relief&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Our case report suggests that transition from subcutaneous treprostinil to oral selexipag under strict clinical supervision may be a safe option for patients with controlled PAH&#44; avoiding the undesirable side effects related to parenteral administration&#44; meanwhile maintaining clinical stability&#46; There is little experience with transition to oral selexipag from parenteral prostacyclin therapy&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> and our patient represents the first case of a subcutaneous treprostinil to oral selexipag switch&#46; Further investigation is required to clarify whether the route of administration may influence efficacy and safety profile&#44; and to help characterizing the patients that may benefit from this transition&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Finally&#44; it should be noted that&#44; we have relied on non-invasive prognostic markers &#40;WHO FC&#44; NTproBNP and 6MWD&#41; for patient risk profile assessment since they have been validated recently in follow-up&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> added to patient&#39;s refusal to undergo another right heart catheterization&#46; We added echocardiography and CPET in order to increase accuracy taking into account the lack of invasive data&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In conclusion&#44; this case highlights how a safe transition from parenteral to oral prostacyclin pathway therapy in a stable PAH patient is possible&#46; Thereby&#44; avoiding the unbearable side effects associated with the parental route of prostacyclin administration&#46;</p></span>"
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0035" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0010"
          ]
        ]
      ]
    ]
    "multimedia" => array:2 [
      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">6MWD&#58; 6<span class="elsevierStyleHsp" style=""></span>minutes walking distance&#59; CPET&#58; cardiopulmonary exercise test&#59; VO<span class="elsevierStyleInf">2</span>&#58; oxygen uptake&#59; RA&#58; right atrium&#59; RAP&#58; right atrial pressure&#59; SvO<span class="elsevierStyleInf">2</span>&#160;&#61;&#160;mixed venous oxygen saturation&#59; CI&#58; cardiac index&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tablaImagen" => array:1 [
                0 => array:4 [
                  "imagenFichero" => "fx1.jpeg"
                  "imagenAlto" => 1910
                  "imagenAncho" => 3167
                  "imagenTamanyo" => 575791
                ]
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Risk Profile Assessment&#46;</p>"
        ]
      ]
      1 => array:6 [
        "identificador" => "upi0005"
        "tipo" => "MULTIMEDIAECOMPONENTE"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "Ecomponente" => array:2 [
          "fichero" => "mmc1.docx"
          "ficheroTamanyo" => 234405
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Transition treatment algorithm &#40;bid&#58; every 12<span class="elsevierStyleHsp" style=""></span>h&#41;&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:6 [
            0 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2015 ESC&#47;ERS Guidelines for the diagnosis and treatment of pulmonary hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "N&#46; Gali&#232;"
                            1 => "M&#46; Humbert"
                            2 => "J&#46;-L&#46; Vachiery"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur Heart J"
                        "fecha" => "2016"
                        "volumen" => "37"
                        "paginaInicial" => "67"
                        "paginaFinal" => "119"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prostanoid therapy for pulmonary arterial hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "D&#46;B&#46; Badesch"
                            1 => "V&#46;V&#46; McLaughlin"
                            2 => "M&#46; Delcroix"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2004"
                        "volumen" => "16"
                        "paginaInicial" => "56S"
                        "paginaFinal" => "61S"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treprostinil for pulmonary hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "N&#46; Skoro-Sajer"
                            1 => "I&#46; Lang"
                            2 => "R&#46; Naeije"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Vasc Health Risk Manag"
                        "fecha" => "2008"
                        "volumen" => "4"
                        "paginaInicial" => "507"
                        "paginaFinal" => "513"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18827901"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "GRIPHON study&#46; Selexipag for the treatment of pulmonary arterial hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "O&#46; Sitbon"
                            1 => "R&#46; Channick"
                            2 => "K&#46;M&#46; Chin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2015"
                        "volumen" => "373"
                        "paginaInicial" => "2522"
                        "paginaFinal" => "2533"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Transition from parental prostacyclin therapy to oral selexipag in pulmonary arterial hypertension&#58; a single center case series &#91;abstract&#93;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "E&#46; Mims"
                            1 => "D&#46; Poch"
                            2 => "D&#46; Papamatheakis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "J Heart Lung Transpl"
                        "fecha" => "2017"
                        "volumen" => "36"
                        "paginaInicial" => "S362"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk assessment&#44; prognosis and guideline implementation in pulmonary arterial hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Boucly"
                            1 => "J&#46; Weatherald"
                            2 => "L&#46; Savale"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/13993003.00889-2017"
                      "Revista" => array:2 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2017"
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/03002896/0000005500000002/v1_201902020631/S0300289618301546/v1_201902020631/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "49741"
    "tipo" => "SECCION"
    "es" => array:2 [
      "titulo" => "Scientific Letters / Cartas cient&#237;ficas"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "es"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/03002896/0000005500000002/v1_201902020631/S0300289618301546/v1_201902020631/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289618301546?idApp=UINPBA00003Z"
]
Share
Journal Information
Vol. 55. Issue 2.
Pages 102-103 (February 2019)
Share
Share
Download PDF
More article options
Vol. 55. Issue 2.
Pages 102-103 (February 2019)
Scientific Letter
Full text access
Living With Severe Pulmonary Arterial Hypertension Without an Infusion Pump? Selexipag has a Role to Play
¿Viviendo con hipertensión arterial pulmonar grave sin una bomba de infusión? Selexipag tiene un papel
Visits
4259
María Lázaro Salvadora,
Corresponding author
maria.lasal@gmail.com

Corresponding author.
, Finn Akerströma, Pilar Escribano Subíasb, Alejandro Berenguel Senéna, Virgilio Martinez Mateoc, Luis Rodriguez Padiala
a Department of Cardiology, Hospital Virgen de la Salud, Toledo, Spain
b Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain
c Department of Cardiology, Hospital La Mancha Centro, Alcazar de San Juan, Spain
This item has received
Article information
Full Text
Bibliography
Download PDF
Statistics
Tables (1)
Table 1. Risk Profile Assessment.
Additional material (1)
Full Text
Dear Editor,

Pulmonary arterial hypertension (PAH) is a rare disease characterized by cellular proliferation and vasoconstriction of the pulmonary arterial bed. PAH is a devastating disease with a high mortality despite available therapy.1 Three well-known pathways are involved in PAH pathophysiology (endothelin, nitric oxide, and prostacyclin), which are all therapeutic targets. The updated ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension recommend prostacyclin analogues in patients suffering from severe PAH, referring to WHO functional class (FC) III and IV.1 Prostacyclin is an endogenous prostanoid, that induces vasodilatation and inhibits platelet aggregation and cell proliferation, and patients with PAH present decreased prostacyclin production.2 Treprostinil, as prostacyclin analogue, is metabolically stable, long-acting, and can be administered subcutaneously using a portable small delivery system.3 Although subcutaneous administration implies less risk of systemic infection or catheter dislocation, subcutaneous infections and severe pain at infusion site are common and may make further treatment impossible in 7%–10% of the patients.3 Selexipag is a novel orally available non-prostacyclin selective prostacyclin receptor (IP receptor) agonist. Following absorption, it is hydrolyzed to an active more potent metabolite, which has a 7.9-h half-life, allowing for twice daily dosing. Common side effects (all drug class related) include headache, diarrhea, jaw pain, nausea, myalgia, vomiting, and flushings. Selexipag has shown efficacy in PAH, even in sequential triple combination,4 and it is currently approved for the treatment of PAH patients in WHO FC II-III, both in combination with endothelin receptor antagonist (ERA) and/or phosphodiesterase 5 inhibitors (iPDE-5) or in monotherapy.1 Given its oral administration, selexipag avoids the complications related to continuous parenteral administration. Hence, switching to selexipag maybe an attractive option in patients who were once started on a parental prostacyclin. However, little is known with regards to the aforementioned drug switch.5 Here, we present a successful case of transition from subcutaneous treprostinil to selexipag in a PAH patient reporting unbearable adverse events associated with treprostinil subcutaneous administration (Appendix A).

In August 2011 a 54-year-old woman was referred to our PAH Unit due to severe idiopathic PAH with a high-risk profile according to the prognosis assessment table suggested by current guidelines1 (Table 1A). After six months of combination therapy with the iPDE-5 sildenafil (80mg/8h) and the ERA ambrisentan (10mg/24h), the patient improved and achieved every low risk criteria (Table 1A). Later on, sildenafil was switched to the iPDE-5 tadalafil 40mg/24h due to nasal congestion. Following this, the patient remained stable in the low risk profile for two additional years. In early 2014, the patient deteriorated to the intermediate risk profile (Table 1A) and subcutaneous treprostinil was added and titrated up to 30ng/kg/min. With the triple regime (ERA + iPDE-5 + treprostinil), she quickly recovered her previous low-risk profile and remained stable for another 32 months. Unfortunately, our patient insistently complained about unbearable pain around treprostinil infusion site, and several subcutaneous infections were reported. Consequently, we planned progressive transition from subcutaneous treprostinil to oral selexipag after non-invasive risk profile assessment (Table 1B). Patient refused right heart catheterization. Progressive treprostinil down-titration and simultaneous selexipag up-titration was performed in outpatient clinic, under close supervision, throughout 8 weeks, so that every week, 4ng/kg/min of treprostinil were reduced and 200μg/12h were added. During the first 4 days of selexipag intake, patient reported mild diarrhoea, self-limited within the first week. No other side effects were reported. Patient ended up taking maximal doses of oral selexipag 1600μg/12h, plus her previous tadalafil and ambrisentan combination therapy unvaried. Six months after treprostinil withdrawal, the patient risk profile had slightly improved (Table 1B). Her functional capacity was better (both in 6min walking test distance and in cardiopulmonary exercise test) and quality of life drastically increased; not having to carry the infusion pump was a great relief.

Table 1.

Risk Profile Assessment.

6MWD: 6minutes walking distance; CPET: cardiopulmonary exercise test; VO2: oxygen uptake; RA: right atrium; RAP: right atrial pressure; SvO2 = mixed venous oxygen saturation; CI: cardiac index.

Our case report suggests that transition from subcutaneous treprostinil to oral selexipag under strict clinical supervision may be a safe option for patients with controlled PAH, avoiding the undesirable side effects related to parenteral administration, meanwhile maintaining clinical stability. There is little experience with transition to oral selexipag from parenteral prostacyclin therapy,5 and our patient represents the first case of a subcutaneous treprostinil to oral selexipag switch. Further investigation is required to clarify whether the route of administration may influence efficacy and safety profile, and to help characterizing the patients that may benefit from this transition.

Finally, it should be noted that, we have relied on non-invasive prognostic markers (WHO FC, NTproBNP and 6MWD) for patient risk profile assessment since they have been validated recently in follow-up,6 added to patient's refusal to undergo another right heart catheterization. We added echocardiography and CPET in order to increase accuracy taking into account the lack of invasive data.

In conclusion, this case highlights how a safe transition from parenteral to oral prostacyclin pathway therapy in a stable PAH patient is possible. Thereby, avoiding the unbearable side effects associated with the parental route of prostacyclin administration.

Appendix A
Supplementary data

Transition treatment algorithm (bid: every 12h).

References
[1]
N. Galiè, M. Humbert, J.-L. Vachiery, et al.
2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.
Eur Heart J, 37 (2016), pp. 67-119
[2]
D.B. Badesch, V.V. McLaughlin, M. Delcroix, et al.
Prostanoid therapy for pulmonary arterial hypertension.
J Am Coll Cardiol, 16 (2004), pp. 56S-61S
[3]
N. Skoro-Sajer, I. Lang, R. Naeije.
Treprostinil for pulmonary hypertension.
Vasc Health Risk Manag, 4 (2008), pp. 507-513
[4]
O. Sitbon, R. Channick, K.M. Chin, et al.
GRIPHON study. Selexipag for the treatment of pulmonary arterial hypertension.
N Engl J Med, 373 (2015), pp. 2522-2533
[5]
E. Mims, D. Poch, D. Papamatheakis, et al.
Transition from parental prostacyclin therapy to oral selexipag in pulmonary arterial hypertension: a single center case series [abstract].
J Heart Lung Transpl, 36 (2017), pp. S362
[6]
A. Boucly, J. Weatherald, L. Savale, et al.
Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension.
Copyright © 2018. SEPAR
Archivos de Bronconeumología
Article options
Tools

Are you a health professional able to prescribe or dispense drugs?