Editorial comment
Renin-angiotensin-aldosterone system inhibitors and the COVID-19 epidemic
Os inibidores do sistema Renina-Angiotensina-Aldosterona e a epidemia Covid-19
Lido
1634
Vezesque se leu este artigo
608
Total PDF
1026
Total HTML
Compartilhar estatísticas
array:24 [ "pii" => "S0870255122003614" "issn" => "08702551" "doi" => "10.1016/j.repc.2022.08.006" "estado" => "S300" "fechaPublicacion" => "2022-10-01" "aid" => "2026" "copyright" => "Sociedade Portuguesa de Cardiologia" "copyrightAnyo" => "2022" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2022;41:831-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:19 [ "pii" => "S0870255122002578" "issn" => "08702551" "doi" => "10.1016/j.repc.2021.06.022" "estado" => "S300" "fechaPublicacion" => "2022-10-01" "aid" => "1976" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2022;41:833-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Alteration in serum oxidative stress balance in patients with different circulating high-density lipoprotein cholesterol levels" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "833" "paginaFinal" => "839" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Alteração do equilíbrio do <span class="elsevierStyleItalic">stress</span> oxidativo sérico em doentes com diferentes níveis circulatórios de colesterol HDL" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1333 "Ancho" => 1675 "Tamanyo" => 93348 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Linear regression analysis between serum TAC and HDL-C levels. Serum TAC levels (β=-0.309, 95% CI: -78.471-28.734, p<0.001) were dependently associated with HDL-C values. For abbreviations see text.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Mustafa Karabacak, Bayram Ali Uysal, Ahmet Kenan Turkdogan" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Mustafa" "apellidos" => "Karabacak" ] 1 => array:2 [ "nombre" => "Bayram Ali" "apellidos" => "Uysal" ] 2 => array:2 [ "nombre" => "Ahmet Kenan" "apellidos" => "Turkdogan" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255122002578?idApp=UINPBA00004E" "url" => "/08702551/0000004100000010/v1_202210061538/S0870255122002578/v1_202210061538/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0870255122002554" "issn" => "08702551" "doi" => "10.1016/j.repc.2021.06.021" "estado" => "S300" "fechaPublicacion" => "2022-10-01" "aid" => "1975" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2022;41:823-30" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Impact of the withdrawal of renin-angiotensin-aldosterone inhibitors on mortality in COVID-19 patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "823" "paginaFinal" => "830" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Impacto da retirada dos inibidores do sistema renina-angiotensina-aldosterona na mortalidade dos doentes com Covid-19" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1186 "Ancho" => 1675 "Tamanyo" => 110918 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier survival analysis among all patients with RAASi treatment. Patients discontinuing both an angiotensin converting enzyme inhibitors/angiotensin receptor blockers plus a mineralocorticoid receptor antagonists showed the worst prognosis.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Juan Caro-Codón, Juan R. Rey, Angel M. Iniesta, Sandra O. Rosillo, Sergio Castrejon-Castrejon, Laura Rodriguez-Sotelo, Jose M. Garcia-Veas, Irene Marco, Luis A. Martinez, Lorena Martin-Polo, Carlos Merino, Marcel Martinez-Cossiani, Antonio Buño, Luis Gonzalez-Valle, Alicia Herrero, Esteban López-de-Sá, Jose L. Merino" "autores" => array:18 [ 0 => array:2 [ "nombre" => "Juan" "apellidos" => "Caro-Codón" ] 1 => array:2 [ "nombre" => "Juan R." "apellidos" => "Rey" ] 2 => array:2 [ "nombre" => "Angel M." "apellidos" => "Iniesta" ] 3 => array:2 [ "nombre" => "Sandra O." "apellidos" => "Rosillo" ] 4 => array:2 [ "nombre" => "Sergio" "apellidos" => "Castrejon-Castrejon" ] 5 => array:2 [ "nombre" => "Laura" "apellidos" => "Rodriguez-Sotelo" ] 6 => array:2 [ "nombre" => "Jose M." "apellidos" => "Garcia-Veas" ] 7 => array:2 [ "nombre" => "Irene" "apellidos" => "Marco" ] 8 => array:2 [ "nombre" => "Luis A." "apellidos" => "Martinez" ] 9 => array:2 [ "nombre" => "Lorena" "apellidos" => "Martin-Polo" ] 10 => array:2 [ "nombre" => "Carlos" "apellidos" => "Merino" ] 11 => array:2 [ "nombre" => "Marcel" "apellidos" => "Martinez-Cossiani" ] 12 => array:2 [ "nombre" => "Antonio" "apellidos" => "Buño" ] 13 => array:2 [ "nombre" => "Luis" "apellidos" => "Gonzalez-Valle" ] 14 => array:2 [ "nombre" => "Alicia" "apellidos" => "Herrero" ] 15 => array:2 [ "nombre" => "Esteban" "apellidos" => "López-de-Sá" ] 16 => array:2 [ "nombre" => "Jose L." "apellidos" => "Merino" ] 17 => array:1 [ "colaborador" => "on behalf of the CARD-COVID Investigators (Appendix)" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255122002554?idApp=UINPBA00004E" "url" => "/08702551/0000004100000010/v1_202210061538/S0870255122002554/v1_202210061538/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Renin-angiotensin-aldosterone system inhibitors and the COVID-19 epidemic" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "831" "paginaFinal" => "832" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "José Silva-Cardoso, Emilia Moreira" "autores" => array:2 [ 0 => array:4 [ "nombre" => "José" "apellidos" => "Silva-Cardoso" "email" => array:1 [ 0 => "silvacardoso30@gmail.com" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Emilia" "apellidos" => "Moreira" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Faculdade de Medicina da Universidade do Porto, Porto, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro Hospitalar Universitário de São João, Porto, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "RISE – Rede de Investigação em Saúde, Laboratório Associado, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Os inibidores do sistema Renina-Angiotensina-Aldosterona e a epidemia Covid-19" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">This editorial comment refers to the article “Impact of renin-angiotensin-aldosterone inhibitors withdrawal on mortality in COVID-19 patients” by Caro-Codón et al., published in this issue of the Revista Portuguesa de Cardiologia.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The anchor-point of SARS-CoV-2 in human cell membranes, specifically in the respiratory epithelium, is a protein called angiotensin-converting enzyme-2 (ACE-2). Once attached to this protein, internalization vesicles are formed and the virus enters the cytoplasm. The consequence of SARS-CoV-2 virus binding to ACE-2 and the resulting internalization of these molecules is a decrease in ACE-2 on the epithelial cells’ surface.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Contrary to angiotensin-converting enzyme-1 (ACE-1), which promotes the conversion of angiotensin-<span class="elsevierStyleSmallCaps">I</span> into angiotensin-<span class="elsevierStyleSmallCaps">II</span>, thus increasing serum concentrations of the latter, ACE-2 reduces angiotensin-<span class="elsevierStyleSmallCaps">II</span> levels by transforming it into angiotensin.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–7</span></a> Angiotensin-<span class="elsevierStyleSmallCaps">II</span> has deleterious effects which include vasoconstriction, sodium retention, cell proliferation, apoptosis, fibrosis, and inflammation. Angiotensin<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–7</span></a> has diametrically opposed protective effects.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">.</span><a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Lung damage, cardiac remodeling, inflammation, and vasoconstriction are harmful consequences of an overproduction of angiotensin-<span class="elsevierStyleSmallCaps">II</span>.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">SARS-CoV-2, by docking on ACE-2, with the consequent internalization of the virus/ACE-2 complex, reduces the number of ACE-2 molecules available at the cell surface (specifically at the respiratory epithelium level), leading to a decrease in the amount of protective angiotensin 1-7 molecules and an increase in harmful angiotensin-<span class="elsevierStyleSmallCaps">II</span> molecules, with a consequent exaggerated inflammatory response.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2–5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">At the beginning of the SARS-CoV-2 epidemic, it was thought that this infection could be aggravated by ACE inhibitors (ACEi) and by angiotensin receptor blockers (ARB), which supposedly could facilitate SARS-CoV-2 infection by increasing ACE-2 levels at epithelial cells’ surface, creating an opportunity for SARS-CoV-2 to anchor and then be internalized into target cells, specifically those of the respiratory epithelium, infecting them.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a> In fact, a paper published in Circulation in 2005<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> showed that ACEis did increase ACE-2 molecules at the epithelial cells’ surface and the same occurred with ARBs.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> It was, therefore, assumed that these drugs could indeed create greater opportunities for SARS-CoV-2 to cause injury.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">This created a wave of suspicion regarding these drugs leading to their discontinuation, particularly in patients with cardiovascular diseases, in which they play a central role in improving prognosis.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">However, the study by Caro-Codón et al. now published in the Journal, showed that, in patients with cardiovascular disease infected with SARS-CoV-2, the discontinuation of ACEis or mineralocorticoid receptor antagonists (MRAs) was in fact associated with an increase in all-cause mortality, compared to patients in whom these drugs were not withdrawn.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">This study is consistent with others previously published, especially one by Savarese et al.,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> demonstrating, in an extensive cohort of 1.4 million patients with arterial hypertension, heart failure, diabetes, kidney disease, or coronary heart disease, that the use of ACEIs/ARBs was associated with a reduced risk of hospitalization/mortality due to COVID-19 infection.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Therefore, the study by Savarese et al.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> does not confirm the fears of a possible negative association of ACEIs/ARBs with a worsened COVID-19 infection prognosis.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,8</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Despite these reassuring data, randomized studies are needed to determine the role of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients infected with COVID-19.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,8</span></a> The BRACE CORONA study, including 659 cardiovascular patients with mild to moderate forms of COVID-19 infection who were randomized to continuation <span class="elsevierStyleItalic">vs.</span> discontinuation of ACEis/ARBs, proved that the maintenance of these drugs was safe, and was not associated with increased mortality.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In summary, current evidence does not demonstrate that RAASi are effective against COVID-19 infection, but it clearly suggests that, in this context, they are safe and, therefore, they should be maintained in patients with heart failure, hypertension, diabetes, coronary heart disease and kidney disease, even if infected with COVID-19, taking into account their proven positive prognostic impact in patients with these cardiovascular disorders.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,5,8,9</span></a></p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of renin-angiotensin-aldosterone inhibitors withdrawal on mortality in COVID-19 patients" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "on behalf of the CARD-COVID Investigators" "etal" => true "autores" => array:3 [ 0 => "J. Caro-Codón" 1 => "J.R. Rey" 2 => "A.M. Iniesta" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.repc.2021.06.021" "Revista" => array:6 [ "tituloSerie" => "Rev Port Cardiol" "fecha" => "2022" "volumen" => "41" "paginaInicial" => "823" "paginaFinal" => "830" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35784098" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0060" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G. de Simone" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Position statement of the ESC council on hypertension on ACE-inhibitors and angiotensin receptor blockers" "fecha" => "2020" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0065" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renin–angiotensin–aldosterone system blockers and the risk of Covid-19" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "G. Mancia" 1 => "F. Rea" 2 => "M. Ludergnani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM198307073090101" "Revista" => array:5 [ "tituloSerie" => "N Engl J Med" "fecha" => "2020" "paginaInicial" => "1" "paginaFinal" => "10" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6855851" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0070" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renin–angiotensin–aldosterone system inhibitors and risk of Covid-19" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "H.R. Reynolds" 1 => "S. Adhikari" 2 => "C. Pulgarin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM198307073090101" "Revista" => array:5 [ "tituloSerie" => "N Engl J Med" "fecha" => "2020" "paginaInicial" => "1" "paginaFinal" => "8" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6855851" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0075" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renin-angiotensin-aldosterone inhibitors and COVID-19: nearing the end of a media-fuelled controversy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "D. Tomasoni" 1 => "M.C. Petrie" 2 => "M. Adamo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ejhf.2098" "Revista" => array:6 [ "tituloSerie" => "Eur J Heart Fail" "fecha" => "2021" "volumen" => "23" "paginaInicial" => "486" "paginaFinal" => "488" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33421242" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0080" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rapid response: could ACE inhibitors, and particularly ARBs, increase susceptibility to COVID-19 infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G.J. O’Mara" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bmj.m406" "Revista" => array:5 [ "tituloSerie" => "BMJ" "fecha" => "2020" "volumen" => "368" "paginaInicial" => "m406" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32005675" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0085" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C.M. Ferrario" 1 => "J. Jessup" 2 => "M.C. Chappell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.104.510461" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2005" "volumen" => "111" "paginaInicial" => "2605" "paginaFinal" => "2610" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15897343" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0090" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association between renin-angiotensin-aldosterone system inhibitor use and COVID-19 hospitalization and death: a 1.4 million patient nationwide registry analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "G. Savarese" 1 => "L. Benson" 2 => "J. Sundström" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ejhf.2060" "Revista" => array:6 [ "tituloSerie" => "Eur J Heart Fail" "fecha" => "2021" "volumen" => "23" "paginaInicial" => "476" "paginaFinal" => "485" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33222412" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0095" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "European Society of Cardiology. First randomised trial backs safety of common heart drugs in COVID-19 patients. Available at: <a target="_blank" href="https://www.escardio.org/The-ESC/Press-Office/Press-releases/LOPES">https://www.escardio.org/The-ESC/Press-Office/Press-releases/LOPES</a> [accessed 25.11.20]." ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/08702551/0000004100000010/v1_202210061538/S0870255122003614/v1_202210061538/en/main.assets" "Apartado" => array:4 [ "identificador" => "92834" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/08702551/0000004100000010/v1_202210061538/S0870255122003614/v1_202210061538/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255122003614?idApp=UINPBA00004E" ]
| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 8 | 8 | 16 |
| 2024 Outubro | 55 | 37 | 92 |
| 2024 Setembro | 69 | 24 | 93 |
| 2024 Agosto | 58 | 30 | 88 |
| 2024 Julho | 55 | 32 | 87 |
| 2024 Junho | 47 | 21 | 68 |
| 2024 Maio | 37 | 20 | 57 |
| 2024 Abril | 59 | 27 | 86 |
| 2024 Maro | 48 | 21 | 69 |
| 2024 Fevereiro | 47 | 30 | 77 |
| 2024 Janeiro | 38 | 16 | 54 |
| 2023 Dezembro | 27 | 24 | 51 |
| 2023 Novembro | 19 | 18 | 37 |
| 2023 Outubro | 15 | 15 | 30 |
| 2023 Setembro | 16 | 18 | 34 |
| 2023 Agosto | 11 | 9 | 20 |
| 2023 Julho | 25 | 13 | 38 |
| 2023 Junho | 18 | 12 | 30 |
| 2023 Maio | 30 | 18 | 48 |
| 2023 Abril | 22 | 6 | 28 |
| 2023 Maro | 26 | 18 | 44 |
| 2023 Fevereiro | 36 | 16 | 52 |
| 2023 Janeiro | 21 | 17 | 38 |
| 2022 Dezembro | 49 | 23 | 72 |
| 2022 Novembro | 60 | 43 | 103 |
| 2022 Outubro | 118 | 78 | 196 |
| 2022 Setembro | 12 | 14 | 26 |
Mostrar tudo
