Original article
Cardiovascular involvement in patients with diabetic macular oedema treated with intravitreal ranibizumab in routine clinical practice
Afectación cardiovascular en pacientes con edema macular diabético tratados con ranibizumab intravítreo en la práctica clínica habitual
R. Díaz-Rodrígueza,
, R. Abreu-Gonzáleza, R. Dolz-Marcob,c, R. Gallego-Pinazob,c
Corresponding author
a Servicio de Oftalmología, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain
b Unidad de Mácula, Servicio de Oftalmología, Hospital Universitario y Politécnico La Fe, Valencia, Spain
c RETICS RD160008 Enfermedades oculares, Prevención, detección precoz, tratamiento y rehabilitación de las patologías oculares, Valencia, Spain
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"apellidos" => "Gallego-Pinazo" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Oftalmología, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Mácula, Servicio de Oftalmología, Hospital Universitario y Politécnico La Fe, Valencia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "RETICS RD160008 Enfermedades oculares, Prevención, detección precoz, tratamiento y rehabilitación de las patologías oculares, Valencia, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Afectación cardiovascular en pacientes con edema macular diabético tratados con ranibizumab intravítreo en la práctica clínica habitual" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1544 "Ancho" => 1307 "Tamanyo" => 58196 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Distribution of bilateral treatment of patients included in the study.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">At present, diabetes mellitus (DM) affects over 340 million people worldwide<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> and has become one of the most severe health problems of our time, not only due to the high and rising prevalence but due to the multiple complications it entails. One of the most relevant ocular complications, with a prevalence of 7.9% among the Spanish population with DM type 2,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> is diabetic macular oedema (DME) which has become the main cause of severe visual impairment in developed countries.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">DME is a process with a multifactorial and complex etiopathogeny<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">3</span></a> that gives rise to different types of macular oedema. The central involvement oedema is the one that compromises visual acuity with greater severity and accordingly the one that benefits more from antiangiogenic therapy. Intravitreal ranibizumab (RBZ), that has demonstrated excellent results in multicenter clinical trials carried out to date,<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">4–8</span></a> is one of the anti-VEGF treatments indicated for DME<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">9</span></a>. However, and even though the adverse effects of intravitreal anti-VEGF are mainly ocular, its use involves a theoretical and potential risk of systemic arterial thromboembolic events (hemorrhages, CVA, AMI),<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">9</span></a> and this has raised doubts about its systemic safety.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The objective of the present study is to analyze the prevalence and incidence of short-term systemic cardiovascular events in naïve patients with DME and central involvement. interpreted as the involvement within the EDTRS area measured with OCT and treated with intravitreal RBZ as monotherapy in the context of routine clinical practice at the <span class="elsevierStyleItalic">Hospital Universitario Nuestra Señora de Candelaria</span> (HUNSC) and at the <span class="elsevierStyleItalic">Hospital Universitario y Politécnico La Fe</span>.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Subjects, material and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">A descriptive and retrospective study of patients with DME and central involvement without previous treatment <span class="elsevierStyleItalic">(naïve)</span> who initiated intravitreal RBZ in monotherapy between January and December 2014 at the HUNSC of Tenerife or the <span class="elsevierStyleItalic">Hospital Universitario y Politécnico La Fe</span> of Valencia.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The endpoint of the study was set in August 2015 and 17 variables were studied: age, sex, weight, height, body mass index, tobacco smoking, arterial hypertension (AHT), dyslipidemia, DM type, years of evolution thereof, use of insulin, use of oral antidiabetics, glycosylated hemoglobin (Hb1Ac), AMI before and after ocular treatment and CVA 4 and after ocular treatment.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Data were obtained from the computer clinic records both from primary care as well as specialized attention for the general and systemic variables. as well as the specific computer clinic history of the Ophthalmology Dept. for ophthalmological variables. The statistical analysis was carried out with the SPSS v.15.0 application (SPSS Inc. Chicago, IL, USA), utilizing the McNemar test.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">Of the 1324 intravitreal RBZ injections (572 HUNSC, 752 <span class="elsevierStyleItalic">La Fe</span>) administered in 2014 under DME indication only 159 were initial treatment, administered to 99 patients (76 HUNSC, 23 <span class="elsevierStyleItalic">La Fe</span>), as over half of these (58.6%) required treatment in both eyes (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The mean number of treatments was 3.55<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.27 (range 12) with a mean follow-up of 9.53<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.87 months (range 17). The baseline epidemiological and metabolic characteristics of the patients included in the study are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Fifty-eight of the 99 patients were male (58.6%) and 41 were female (41.4%), with a mean age of 63.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.7 years (range 59) and 69.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.6 years (range 36), respectively. The majority of patients were not smokers (85.9%) but exhibited hypertension (70.7%) and dyslipidemia (65.7%). Out of the 6 patients with previous AMI, only one (16.6%) was a smoker and out of the 8 patients with previous CVA, only one (12.5%) was a smoker.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Overall, 91.9% were diabetics type 2, with a mean of 16.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.1 (range 47) years evolution, and combined treatment (70.7% insulin, 72.7% oral diabetics) and with a mean Hb1Ac of 7.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.6% (range 7.80).</p><p id="par0050" class="elsevierStylePara elsevierViewall">In what concerns systemic cardiovascular events, 6 patients had AMI and 8 CVA before the ocular treatment with RBZ, a prevalence in this series of 6.1% and 8.1% respectively. In what concerns incidence, only one (1%) of patients exhibited CVA after intravitreal treatment (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.039), which occurred 6 months after the treatment and in the context of bacterian meningitis. No case of post-treatment AMI was registered (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.031).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">The results of the study, derived from the analysis of a sample of patients with diabetes obtained from usual clinical practice, represents the profile of a patient matching the description previously found in the literature, i.e., ocular involvement occurring in the context of poorly controlled diabetes<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">10,11</span></a> and with long evolution<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">10,12</span></a> to which common cardiovascular risk factors are associated, including AHT<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">10,11</span></a> and dyslipidemia.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">10,12</span></a> In addition, the rate of stroke and AMI is twice that exhibited by diabetes patients without diabetic retinopathy.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">On the other hand, just like the other intraocular anti-VEGF, intravitreal RBZ has been associated (although in low frequency) to a potential unconfirmed risk of systemic cardiovascular adverse events such as hemorrhages, CVA and AMI.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">9</span></a> To this we must add the existence of limited data as regards the safety of these drugs in patients with a history of CVA and AMI, and that patients with DME have a higher risk of systemic absorption despite local administration<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a>. The systemic half life of RBZ is a fraction of the half life of aflibercept (2<span class="elsevierStyleHsp" style=""></span>h against 5–6 days respectively) according to the description of their technical information.<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">14,15</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The present study shows that intravitreal RBZ in monotherapy in naïve patients with central involvement DME could constitute a safe alternative because, despite high systemic cardiovascular risk, the prevalence of adverse cardiovascular events was similar to that of the general population<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">16</span></a> and the incidence was only 1%.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The hypothesis of the authors follows the line indicated in different studies, mostly part of a meta-analysis of randomized trials published in 2014 by Yanagida and Ueta<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">17</span></a> who evaluated the systemic safety of RBZ in patients with DME. Said study included 6 of the most important multicenter clinical trials that compared RBZ with or without combined laser against controls (RESOLVE,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">8</span></a> RISE & RIDE,<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">18,19</span></a> DRCR.net,<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">6,20</span></a> RESTORE,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> REVEAL,<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a> READ-2<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a>). Said study included 2459 patients comparing, among other variables, the frequency of systemic adverse effects such as CVA and AMI. As regards the former, no statistically significant differences were found between the control and the treatment groups (RR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.80; 0.37–1.73), as well as in the frequency of AMI (RR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.91; 0.46–1.80). <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> illustrates the number of CVA and AMI observed in each trial.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">It must be pointed out that 5 of the included trials excluded patients with a history of CVA<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">5,7,17,19,20</span></a> and 3 excluded patients with history of AMI.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7,17,19</span></a> Kidney insufficiency was also an exclusion criteria in 4 of said studies,<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">6,7,18,21</span></a> while 4 of the 6 studies excluded poor glycemic control<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7,8,18,21</span></a> and 5 excluded poor hypertension control (all except 7) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">On the other hand, intravitreal RBZ has not been studied<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">9</span></a> in patients with liver insufficiency, previous intravitreal injections, active systemic infections, proliferative diabetic retinopathy or concurring ocular diseases such as RD or macular hole, among others. In addition, there is limited experience<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">9</span></a> with patients over 75 years of age, with DM type 1, HbA1c<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>12% and poorly controlled AHT.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Even though the present study did not exclude patients with a history of CVA and AMI, only 5.3% and 7.9% respectively exhibited these adverse effects prior to treatment. Accordingly, the authors consider that additional studies are required for this population type. In addition, the brief follow-up period of the study, limited to 9.53<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.87 months, could be increased in order to analyze longer-term cardiovascular involvement.</p><p id="par0090" class="elsevierStylePara elsevierViewall">It seems logical to conclude that intravitreal RBZ for treating DME is a safe alternative provided that patients are selected on the basis of comorbidities and a PRN regime is followed.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interests</span><p id="par0095" class="elsevierStylePara elsevierViewall">No conflict of interests was declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres856903" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec850949" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres856904" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec850948" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Subjects, material and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-08-09" "fechaAceptado" => "2016-11-05" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec850949" "palabras" => array:3 [ 0 => "Intravitreal ranibizumab" 1 => "Diabetic macular oedema" 2 => "Systemic adverse events" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec850948" "palabras" => array:3 [ 0 => "Ranibizuamb intravítreo" 1 => "Edema macular diabético" 2 => "Eventos sistémicos adversos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To determine the cardiovascular events in naïve patients with diabetic macular oedema, before and after being treated with intravitreal ranibizumab.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A retrospective and descriptive study was conducted on patients with diabetic macular oedema and foveal involvement, who started treatment with intravitreal ranibizumab in 2014 in the Hospital Universitario Nuestra Señora de Candelaria and the Hospital Universitario y Politécnico La Fe. During the follow-up until August 2015, a record was made of parameters, including the prevalence and incidence of stroke and myocardial infarction.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Among the 1324 intravitreal ranibizumab injections administered in 2014, only 159 of them corresponded to treatment initiation in 99 patients, with more than half requiring treatment of both eyes. The study patients included 58.4% males, in the 6th decade of life (mean<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>65.93<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.24 years), non-smokers (86.7%), type 2 diabetes (91.9%), hypertension (70.7%), and with dyslipidaemia (65.7%). Prior to treatment initiation, it was found that 6 patients (6.1%) suffered from an acute myocardial infarction, and 8 (8.1%) from stroke, and only one (1%) with post-stroke (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.039).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In our experience it seems that the intravitreal ranibizumab in diabetic macular oedema could be a safe alternative in patients with a history of stroke and myocardial infarction.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Analizar la afectación cardiovascular a corto plazo de los pacientes <span class="elsevierStyleItalic">naïve</span> con edema macular diabético, tratados con ranibizumab intravítreo, tanto pre- como postratamiento.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo y descriptivo de pacientes con edema macular diabético con afectación central, que hubieran iniciado tratamiento con ranibizumab intravítreo en 2014 en el Hospital Universitario Nuestra Señora de Candelaria y el Hospital Universitario y Politécnico La Fe. Se siguieron hasta agosto de 2015, estudiando, entre otras variables, la prevalencia e incidencia de accidente cerebrovascular y de infarto agudo de miocardio.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">De las 1.324 inyecciones de ranibizumab intravítreo que se administraron en 2014, solo 159 fueron como inicio de tratamiento, repartidas entre un total de 99 pacientes, ya que más de la mitad de ellos precisó tratamiento de ambos ojos (58,6%). El 58,4% de los pacientes fueron hombres, en la sexta década de la vida (X¯=65,93 años<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11,24) y, en su mayoría, no fumadores (86,7%), diabéticos tipo 2 (91,9%), hipertensos (70,7%) y dislipidémicos (65,7%). Se encontraron 6 pacientes (6,1%) con infarto agudo de miocardio y 8 (8,1%) con accidentes cerebrovasculares (ACV) previos al inicio del tratamiento, y solo uno (1%) con accidente cerebrovascular posterior (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,039).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">En nuestra experiencia el ranibizumab intravítreo en pacientes con edema macular diabético, con antecedentes de accidente cerebrovascular e infarto agudo de miocardio podría ser una alternativa segura.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Díaz-Rodríguez R, Abreu-González R, Dolz-Marco R, Gallego-Pinazo R. Afectación cardiovascular en pacientes con edema macular diabético tratados con ranibizumab intravítreo en la práctica clínica habitual. Arch Soc Esp Oftalmol. 2017;92:302–306.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1544 "Ancho" => 1307 "Tamanyo" => 58196 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Distribution of bilateral treatment of patients included in the study.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Yes (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">No (%) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tobacco smokers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">86.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Former smokers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">68.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AHT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dyslipidemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DM type 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DM type 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatment with oral antidiabetics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatment with insulin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1447573.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Baseline epidemiological and metabolic characteristics of study patients.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Clinic trial \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CVA/total patients \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">AMI/total patients \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">READ-2<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/84 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RESTORE<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/235 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/235 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RESOLVE<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">8</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/102 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/102 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DRCR.net<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">6,20</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3/375 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/375 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RISE & RIDE<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">18,19</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11/500 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17/500 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">REVEAL<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/265 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3/265 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1447575.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Distribution of CVA and AMI in different clinic trials.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Clinic trial \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Exclusion criteria \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">READ-2<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CVA and/or AMI within the 6 past months<br>Poorly controlled DM<br>Kidney insufficiency \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DRCR.net<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">6,20</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CVA and/or AMI within the 4 past months<br>Kidney insufficiency<br>Poorly controlled AHT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RESTORE<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Previous CVA<br>Poorly controlled AHT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">REVEAL<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Previous CVA<br>Poorly controlled AHT and/or DM<br>Kidney insufficiency \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RISE & RIDE<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">18,19</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CVA and/or AMI within the past 3 months<br>Poorly controlled AHT and/or DM<br>Kidney insufficiency \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RESOLVE<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">8</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Poorly controlled AHT and/or DM \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1447574.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Distribution of the main exclusion criteria of the different studies.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:21 [ 0 => array:3 [ "identificador" => "bib0110" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of diabetes mellitus and impaired glucose regulation in Spain: the Di@bet.es study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2020 September | 0 | 1 | 1 |
| 2018 February | 4 | 2 | 6 |
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| 2017 May | 0 | 1 | 1 |
