Clinical Report
iPCSK9 treatment of familial hypercholesterolemia in a patient diagnosed as congenital muscular dystrophy with contraindication for statin use
Tratamiento de la hipercolesterolemia familiar con iPCSK9 en un paciente diagnosticado de distrofia muscular congénita con contraindicación para la toma de estatinas
Sergio Arnedo Hernández
, José Daniel Mosquera Lozano, Iratxe Martínez de Narvajas Urra, Estela Menéndez Fernández, Elisa Rabadán Pejenaute, Ramón Baeza Trinidad, Marta Casañas Martínez, Angel Brea Hernando
Corresponding author
Unidad de Lípidos, Servicio de Medicina Interna, Hospital San Pedro, Logroño, La Rioja, Spain
Read
1699
Timeswas read the article
349
Total PDF
1350
Total HTML
Share statistics
array:23 [ "pii" => "S252991231930066X" "issn" => "25299123" "doi" => "10.1016/j.artere.2019.11.001" "estado" => "S300" "fechaPublicacion" => "2019-11-01" "aid" => "480" "copyrightAnyo" => "2019" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Clin Investig Arterioscler. 2019;31:278-81" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S021491681930021X" "issn" => "02149168" "doi" => "10.1016/j.arteri.2019.01.005" "estado" => "S300" "fechaPublicacion" => "2019-11-01" "aid" => "480" "copyright" => "Sociedad Española de Arteriosclerosis" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Clin Invest Arterioscl. 2019;31:278-81" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 22 "formatos" => array:2 [ "HTML" => 7 "PDF" => 15 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Nota clínica</span>" "titulo" => "Tratamiento de la hipercolesterolemia familiar con iPCSK9 en un paciente diagnosticado de distrofia muscular congénita con contraindicación para la toma de estatinas" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "278" "paginaFinal" => "281" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "iPCSK9 treatment of Familial Hypercholesterolemia in a patient diagnosed as Congenital Muscular Dystrophy with contraindication for statin use" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 839 "Ancho" => 1501 "Tamanyo" => 97260 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Evolución del cLDL con los diferentes tratamientos.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Sergio Arnedo Hernández, José Daniel Mosquera Lozano, Iratxe Martínez de Narvajas Urra, Estela Menéndez Fernández, Elisa Rabadán Pejenaute, Ramón Baeza Trinidad, Marta Casañas Martínez, Angel Brea Hernando" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Sergio" "apellidos" => "Arnedo Hernández" ] 1 => array:2 [ "nombre" => "José Daniel" "apellidos" => "Mosquera Lozano" ] 2 => array:2 [ "nombre" => "Iratxe" "apellidos" => "Martínez de Narvajas Urra" ] 3 => array:2 [ "nombre" => "Estela" "apellidos" => "Menéndez Fernández" ] 4 => array:2 [ "nombre" => "Elisa" "apellidos" => "Rabadán Pejenaute" ] 5 => array:2 [ "nombre" => "Ramón" "apellidos" => "Baeza Trinidad" ] 6 => array:2 [ "nombre" => "Marta" "apellidos" => "Casañas Martínez" ] 7 => array:2 [ "nombre" => "Angel" "apellidos" => "Brea Hernando" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S252991231930066X" "doi" => "10.1016/j.artere.2019.11.001" "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/S252991231930066X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S021491681930021X?idApp=UINPBA00004N" "url" => "/02149168/0000003100000006/v3_202004080610/S021491681930021X/v3_202004080610/es/main.assets" ] ] "itemSiguiente" => array:17 [ "pii" => "S2529912319300737" "issn" => "25299123" "doi" => "10.1016/j.artere.2019.11.003" "estado" => "S300" "fechaPublicacion" => "2019-11-01" "aid" => "481" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Clin Investig Arterioscler. 2019;31:282-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "Bleeding risk assessment for stroke patients on antithrombotic therapy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "282" "paginaFinal" => "288" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Evaluación del riesgo hemorrágico de la terapia antitrombótica en pacientes con ictus" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Luis Castilla-Guerra, María del Carmen Fernández-Moreno, Juan Manuel de la Vega-Sánchez, David Leon Jimenez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Luis" "apellidos" => "Castilla-Guerra" ] 1 => array:2 [ "nombre" => "María del Carmen" "apellidos" => "Fernández-Moreno" ] 2 => array:2 [ "nombre" => "Juan Manuel" "apellidos" => "de la Vega-Sánchez" ] 3 => array:2 [ "nombre" => "David" "apellidos" => "Leon Jimenez" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2529912319300737?idApp=UINPBA00004N" "url" => "/25299123/0000003100000006/v1_201912172230/S2529912319300737/v1_201912172230/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S252991231930052X" "issn" => "25299123" "doi" => "10.1016/j.artere.2019.10.001" "estado" => "S300" "fechaPublicacion" => "2019-11-01" "aid" => "499" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Clin Investig Arterioscler. 2019;31:271-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2 "PDF" => 2 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>" "titulo" => "Update of therapeutic planning tables oriented towards obtaining therapeutic objectives" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "271" "paginaFinal" => "277" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Actualización de las tablas de planificación terapéutica hipocolesterolemiante orientadas a la obtención de los objetivos terapéuticos" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 4341 "Ancho" => 3060 "Tamanyo" => 1186563 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">LDL-C value achieved after the administration of PCSK9 inhibitor.</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Mean theoretical value which would be achieved when treating with any of the three therapeutic options of PCSK9 inhibitors available, taking into account the LDL-C value of the patient at the time of the indication, with prior therapy or without prior therapy in the case of intolerant patients.</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The efficacy of PCSK9 inhibitors has been defined as the intermediate value of those reported in the summary of product characteristics for alirocumab 75 mg and evolocumab 140 mg. The value of alirocumab 150 mg has been based on the data from the ODYSSEY LONG TERM study.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Lluís Masana, Núria Plana" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Lluís" "apellidos" => "Masana" ] 1 => array:2 [ "nombre" => "Núria" "apellidos" => "Plana" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0214916819300555" "doi" => "10.1016/j.arteri.2019.04.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0214916819300555?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S252991231930052X?idApp=UINPBA00004N" "url" => "/25299123/0000003100000006/v1_201912172230/S252991231930052X/v1_201912172230/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Clinical Report</span>" "titulo" => "iPCSK9 treatment of familial hypercholesterolemia in a patient diagnosed as congenital muscular dystrophy with contraindication for statin use" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "278" "paginaFinal" => "281" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Sergio Arnedo Hernández, José Daniel Mosquera Lozano, Iratxe Martínez de Narvajas Urra, Estela Menéndez Fernández, Elisa Rabadán Pejenaute, Ramón Baeza Trinidad, Marta Casañas Martínez, Angel Brea Hernando" "autores" => array:8 [ 0 => array:4 [ "nombre" => "Sergio" "apellidos" => "Arnedo Hernández" "email" => array:1 [ 0 => "sarnedo@riojasalud.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "José Daniel" "apellidos" => "Mosquera Lozano" ] 2 => array:2 [ "nombre" => "Iratxe" "apellidos" => "Martínez de Narvajas Urra" ] 3 => array:2 [ "nombre" => "Estela" "apellidos" => "Menéndez Fernández" ] 4 => array:2 [ "nombre" => "Elisa" "apellidos" => "Rabadán Pejenaute" ] 5 => array:2 [ "nombre" => "Ramón" "apellidos" => "Baeza Trinidad" ] 6 => array:2 [ "nombre" => "Marta" "apellidos" => "Casañas Martínez" ] 7 => array:2 [ "nombre" => "Angel" "apellidos" => "Brea Hernando" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Lípidos, Servicio de Medicina Interna, Hospital San Pedro, Logroño, La Rioja, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento de la hipercolesterolemia familiar con iPCSK9 en un paciente diagnosticado de distrofia muscular congénita con contraindicación para la toma de estatinas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 839 "Ancho" => 1501 "Tamanyo" => 99705 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Evolution of cLDL with the different treatments.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Familial hypercholesterolemia (FH) is the most common autosomal dominant genetic disease. It is caused by the mutation of some of the genes that participate in the catabolism of cholesterol bound to low density lipoproteins (cLDL), the most frequent being the one that codes for the LDL receptor. HF is characterised by elevated levels of cLDL and a propensity for early atherosclerotic cardiovascular disease.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 27-year-old male, diagnosed in childhood by genetic study with centronuclear myopathy type muscular dystrophy (recessive inheritance linked to the X chromosome) with inability to take statins. He started at 7 months with hypotonia and skeletal muscle weakness. He was admitted several times due to respiratory failure secondary to the respiratory muscle weakness that occurs. He is currently partially dependent for the basic activities of daily life and walks without help.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Referred to the Lipids Unit of the Hospital San Pedro, Logroño, La Rioja, Spain, because in November 2010 he experienced a total cholesterol (TC) of 286<span class="elsevierStyleHsp" style=""></span>mg/dl and cLDL of 229<span class="elsevierStyleHsp" style=""></span>mg/dl. Both his mother and one of his sisters had higher levels of cLDL than 250<span class="elsevierStyleHsp" style=""></span>mg/dl, despite receiving a pharmacological treatment.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient had no known allergies, was a smoker of 5 cigarettes/day and drank some beer occasionally. He had a congenital muscular dystrophy, a type of centronuclear myopathy diagnosed by muscle biopsy at 10 years of age. Physical examination: body mass index: 23.8<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> and blood pressure: 138/91<span class="elsevierStyleHsp" style=""></span>mmHg. There was no presence of corneal arch, xanthomas or xanthelasmas. Both cardiac and pulmonary auscultation, and the abdominal examination were normal.</p><p id="par0025" class="elsevierStylePara elsevierViewall">A new analysis confirmed hypercholesterolemia: TC: 304<span class="elsevierStyleHsp" style=""></span>mg/dl; cLDL: 235<span class="elsevierStyleHsp" style=""></span>mg/dl; triglycerides: 115<span class="elsevierStyleHsp" style=""></span>mg/dl; cHDL: 46<span class="elsevierStyleHsp" style=""></span>mg/dl; apolipoprotein B (apoB): 153<span class="elsevierStyleHsp" style=""></span>mg/dl; apolipoprotein A1: 146<span class="elsevierStyleHsp" style=""></span>mg/dl and lipoprotein (a): 12<span class="elsevierStyleHsp" style=""></span>mg/dl. The ECG showed sinus tachycardia at 108<span class="elsevierStyleHsp" style=""></span>bpm, without other alterations simple chest and abdomen X-rays showed no relevant alterations.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Treatment with a lipid-lowering diet and ezetimibe 10<span class="elsevierStyleHsp" style=""></span>mg/day was started. When the objective levels of cLDL were not reached after this treatment, both the patient and his first-degree relatives were asked for a genetic study, identifying in him, in his mother and in one of his sisters a pathogenic mutation in heterozygous gene encoding the LDL receptor (M025<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>M080), therefore, he was diagnosed with heterozygous familial hypercholesterolemia (HeFH).</p><p id="par0035" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the chronological evolution of the different treatments that the patient took. In 2014, LDL apheresis was added to the portfolio of services offered by our centre, so by continuing with figures of cLDL 256<span class="elsevierStyleHsp" style=""></span>mg/dl and as there was no therapeutic alternative, he was referred to nephrology. Immediately after the first apheresis session, the cLDL was lowered to 66<span class="elsevierStyleHsp" style=""></span>mg/dl. After 25 sessions of LDL apheresis, the patient was informed of the availability in our centre of PCSK9 inhibitors (iPCSK9). In the first half of 2017, treatment was started with 150<span class="elsevierStyleHsp" style=""></span>mg of alirocumab, biweekly, subcutaneously, and he was able to maintain a plasma concentration of cLDL between 70 and 77<span class="elsevierStyleHsp" style=""></span>mg/dl. Variations of cLDL with the different treatments are shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>. No adverse reactions secondary to treatment with iPCSK9 were detected. Nor was there a worsening of the muscular dystrophy of the patient in terms of the appearance of muscular symptoms, such as myalgia or weakness, nor analysis variations such as the increase in creatine kinase (CK).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0040" class="elsevierStylePara elsevierViewall">Patients with HeFH have elevated cLDL levels from birth, with the consequent premature risk of coronary heart disease. Cholesterol is deposited in the arteries accelerating the formation of atheroma plaques. The prevalence of HeFH is estimated to be one in 300 individuals in Europe and 200–250 in the USA.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The diagnosis of HeFH is made by genetic tests or based on clinical criteria. A mutation in the genes of the LDL, apoB or PCSK9 receptor confirms this diagnosis. When genetic tests are not available, various scoring systems are used for clinical diagnosis, based on cLDL levels, presence of xanthomas or corneal arcus in the physical examination of the patient, personal history of early cardiovascular disease or history of elevated cLDL in first-degree relatives with or without premature cardiovascular disease.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The lipid objective in HeFH is a decrease in cLDL below 70<span class="elsevierStyleHsp" style=""></span>mg/dl. The reduction in cLDL levels has shown a stabilisation, or even the regression of atheroma plaque, which results in a decrease in cardiovascular events, as well as coronary heart disease mortality and overall mortality.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In addition to hygienic-dietary modifications, the first line of pharmacological treatment is statins at the maximum tolerated dose. Most patients with FH do not reach the target levels of cLDL, which forces a second drug to be added: ezetimibe, iPCSK9 or both.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1–4</span></a> If despite these measures an adequate cLDL is not achieved, LDL apheresis can be considered as a third-line therapy.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1,2,5</span></a> The congenital muscular dystrophy presented in our case contraindicates the use of statins because of the risk of worsening the disease with myalgia and rhabdomyolysis. Before the introduction of iPCSK9, the only cholesterol-lowering measures available were resins, ezetimibe and LDL apheresis.</p><p id="par0060" class="elsevierStylePara elsevierViewall">LDL apheresis is the extracorporeal elimination of lipoproteins that contain circulating apoB, including LDL, lipoprotein (a) and VLDL. There are several apheresis methods available and it is usually carried out every week or biweekly. It is currently reserved for patients with homozygous FH or for patients with HeFH who do not achieve objective levels of cLDL despite optimal pharmacological treatment.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">2,6</span></a> The high costs per session and the frequency of treatment represent an important barrier in the treatment of FH.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">iPCSK9s are drugs capable of reducing cLDL up to 60%, associated with statin therapy. They are well-tolerated and safe drugs, with a low adverse event rate and generally of low severity.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">2–5</span></a> Currently, no muscle toxicity or increased CK has been found in patients after administration of iPCSK9.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a> With this new medication, it is possible to space and even avoid treatment with LDL apheresis in patients with HeFH.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">5,6,8</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflict of interests</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1276662" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1180753" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1276661" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1180754" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interests" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-10-18" "fechaAceptado" => "2019-01-24" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1180753" "palabras" => array:3 [ 0 => "Cholesterol-LDL" 1 => "Hypercholesterolemia" 2 => "Muscular dystrophy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1180754" "palabras" => array:3 [ 0 => "Colesterol-LDL" 1 => "Hipercolesterolemia" 2 => "Distrofia muscular" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Statins are contraindicated in patients with myopathies. Until a few years ago, in those patients with familial hypercholesterolemia who also presented muscular dystrophies and did not reach adequate cholesterol plasmatic levels, the next therapeutic ladder was lipoapheresis. When iPCSK9 first appeared, lipoapheresis could be suspended in some of these patients, sustaining nevertheless proper levels of cholesterol.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We present the case of a 27 year-old male, diagnosed with congenital muscular dystrophy in the early childhood. He was referred to the Unit of Lipidology presenting hypercholesterolemia which, after genetic test, was assessed as heterozygous familial hypercholesterolemia. Despite of treatment with diet and ezetimibe, cLDL blood levels abide high, being consequently included in lipoapheresis programme, therewith obtained levels of cLDL of 70<span class="elsevierStyleHsp" style=""></span>mg/dl. In providing iPCSK9, lipoapheresis was withdrawn and treatment with alirocumab 150<span class="elsevierStyleHsp" style=""></span>mg fortnightly introduced, unveiling a positive response, and sustaining cLDL levels around 75<span class="elsevierStyleHsp" style=""></span>mg/dl.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Las estatinas están contraindicadas en pacientes con miopatías. Hasta hace unos años, la alternativa en pacientes con hipercolesterolemia familiar que tenían distrofias musculares y no conseguían niveles adecuados de colesterol era la lipoaféresis. Cuando surgieron los inhibidores de PCSK9, se consiguió suspender la lipoaféresis en algunos de estos pacientes y mantenerlos con concentraciones plasmáticas de colesterol adecuadas.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Presentamos el caso de un varón, diagnosticado en la infancia de distrofia muscular congénita. A los 27 años se remitió a la unidad de lípidos por hipercolesterolemia, donde tras estudio genético se confirmó una hipercolesterolemia familiar heterocigota. A pesar del tratamiento con dieta y ezetimiba continuó con cifras elevadas de cLDL por lo que se incluyó en programa de lipoaféresis. Con esto se alcanzaron niveles de cLDL de 70<span class="elsevierStyleHsp" style=""></span>mg/dl. Al disponer de los iPCSK9, se suspendió la lipoaféresis y se inició tratamiento con alirocumab 150<span class="elsevierStyleHsp" style=""></span>mg quincenal, con buena respuesta y manteniendo valores de cLDL en torno a 75<span class="elsevierStyleHsp" style=""></span>mg/dl.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Arnedo Hernández S, Mosquera Lozano JD, Martínez de Narvajas Urra I, Menéndez Fernández E, Rabadán Pejenaute E, Baeza Trinidad R, et al. Tratamiento de la hipercolesterolemia familiar con iPCSK9 en un paciente diagnosticado de distrofia muscular congénita con contraindicación para la toma de estatinas. Clín Investig Arterioscler. 2019;31:278–281.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1211 "Ancho" => 3189 "Tamanyo" => 348297 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Chronological evolution of the different treatments of the patient.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 839 "Ancho" => 1501 "Tamanyo" => 99705 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Evolution of cLDL with the different treatments.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0045" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Rosenson RS, Durrington P. Familial hypercholesterolemia in adults, in: Gordon M. Saperia, editor, Up to date. Available at: <a target="_blank" href="https://www.uptodate.com/contents/search">https://www.uptodate.com/contents/search</a> [accessed 20.07.18]." ] ] ] 1 => array:3 [ "identificador" => "bib0050" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Rosenson RS, Ferranti SD, Durrington P. Treatment of drug-resistant hypercholesterolemia, in: Gordon M. Saperia, editor, Up to date. Available at: <a target="_blank" href="https://www.uptodate.com/contents/search">https://www.uptodate.com/contents/search</a> [accessed 20.07.18]." ] ] ] 2 => array:3 [ "identificador" => "bib0055" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.J.P. Kastelein" 1 => "H.N. Ginsberg" 2 => "G. Langslet" 3 => "K. Hovingh" 4 => "R. Ceska" 5 => "R. Dufour" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehv370" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2015" "volumen" => "36" "paginaInicial" => "2996" "paginaFinal" => "3003" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26330422" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0060" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab vs. placebo in patients with heterozygous familial hypercholesterolemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.J.P. Kastelein" 1 => "G.K. Hovingh" 2 => "G. Langslet" 3 => "M.T. Baccara-Dinet" 4 => "D.A. Gipe" 5 => "U. Chaudhari" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacl.2016.12.004" "Revista" => array:6 [ "tituloSerie" => "J Clin Lipidol" "fecha" => "2017" "volumen" => "11" "paginaInicial" => "195" "paginaFinal" => "203" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28391886" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0065" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.M. Moriarty" 1 => "K.G. Parhofer" 2 => "S.P. Babirak" 3 => "M.A. Cornier" 4 => "P.B. Duell" 5 => "B. Hohenstein" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehw388" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2016" "volumen" => "37" "paginaInicial" => "3588" "paginaFinal" => "3595" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27572070" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0070" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systematic review of low-density lipoprotein cholesterol apheresis for the treatment of familial hypercholesterolemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Wang" 1 => "A. Richhariya" 2 => "S.R. Gandra" 3 => "B. Calimlim" 4 => "L. Kim" 5 => "R.G.W. Quek" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/JAHA.116.004148" "Revista" => array:4 [ "tituloSerie" => "J Am Heart Assoc" "fecha" => "2016" "volumen" => "5" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27912209" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0075" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Kastelein JJP, Stroes ESG, Stiekema LCA, Rosenson RS. PCSK9 inhibitors: pharmacology, adverse effects, and use, in: Gordon M. Saperia, editor, Up to date. Available at: <a target="_blank" href="https://www.uptodate.com/contents/search">https://www.uptodate.com/contents/search</a> [accessed 13.01.19]." ] ] ] 7 => array:3 [ "identificador" => "bib0080" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Toward an international consensus-Integrating lipoprotein apheresis and new lipid-lowering drugs" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Stefanutti" 1 => "U. Julius" 2 => "G.F. Watts" 3 => "M. Harada-Shiba" 4 => "M. Cossu" 5 => "V.J. Schettler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacl.2017.04.114" "Revista" => array:6 [ "tituloSerie" => "J Clin Lipidol" "fecha" => "2017" "volumen" => "11" "paginaInicial" => "858" "paginaFinal" => "871" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28572002" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/25299123/0000003100000006/v1_201912172230/S252991231930066X/v1_201912172230/en/main.assets" "Apartado" => array:4 [ "identificador" => "81238" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Articulo especial" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/25299123/0000003100000006/v1_201912172230/S252991231930066X/v1_201912172230/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S252991231930066X?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 13 | 0 | 13 |
| 2024 October | 46 | 16 | 62 |
| 2024 September | 68 | 24 | 92 |
| 2024 August | 44 | 15 | 59 |
| 2024 July | 49 | 7 | 56 |
| 2024 June | 51 | 6 | 57 |
| 2024 May | 46 | 5 | 51 |
| 2024 April | 48 | 7 | 55 |
| 2024 March | 29 | 4 | 33 |
| 2024 February | 50 | 5 | 55 |
| 2024 January | 50 | 6 | 56 |
| 2023 December | 41 | 17 | 58 |
| 2023 November | 51 | 24 | 75 |
| 2023 October | 57 | 20 | 77 |
| 2023 September | 44 | 14 | 58 |
| 2023 August | 54 | 12 | 66 |
| 2023 July | 53 | 18 | 71 |
| 2023 June | 45 | 17 | 62 |
| 2023 May | 99 | 18 | 117 |
| 2023 April | 67 | 7 | 74 |
| 2023 March | 40 | 10 | 50 |
| 2023 February | 40 | 7 | 47 |
| 2023 January | 36 | 6 | 42 |
| 2022 December | 38 | 8 | 46 |
| 2022 November | 28 | 4 | 32 |
| 2022 October | 26 | 8 | 34 |
| 2022 September | 27 | 9 | 36 |
| 2022 August | 28 | 11 | 39 |
| 2022 July | 25 | 6 | 31 |
| 2022 June | 14 | 10 | 24 |
| 2022 May | 13 | 5 | 18 |
| 2022 April | 12 | 10 | 22 |
| 2022 March | 10 | 11 | 21 |
| 2022 February | 8 | 2 | 10 |
Show all