{"id":1088,"date":"2021-02-09T10:46:40","date_gmt":"2021-02-09T10:46:40","guid":{"rendered":"http:\/\/localhost\/replace\/racional-y-diseno\/"},"modified":"2025-08-12T12:55:32","modified_gmt":"2025-08-12T12:55:32","slug":"racional-y-diseno","status":"publish","type":"page","link":"https:\/\/www.replace-study.com\/es\/racional-y-diseno\/","title":{"rendered":"Racional y dise\u00f1o"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-page\" data-elementor-id=\"1088\" class=\"elementor elementor-1088\" data-elementor-post-type=\"page\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-6d9d41b9 elementor-section-stretched elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"6d9d41b9\" data-element_type=\"section\" data-e-type=\"section\" data-settings=\"{&quot;stretch_section&quot;:&quot;section-stretched&quot;}\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-no\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-5e0980e\" data-id=\"5e0980e\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-5138566d elementor-widget__width-inherit elementor-widget elementor-widget-shortcode\" data-id=\"5138566d\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"shortcode.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-shortcode\">\n\t\t\t\t<p class=\"rs-p-wp-fix\"><\/p>\n\t\t\t\t<sr7-module data-alias=\"rationale-slider-ES\" data-id=\"16\" id=\"SR7_16_1\" class=\"rs-ov-hidden\" data-version=\"6.7.54\">\n\t\t\t\t\t<sr7-adjuster><\/sr7-adjuster>\n\t\t\t\t\t<sr7-content>\n\t\t\t\t\t\t<sr7-slide id=\"SR7_16_1-8\" data-key=\"8\">\n\t\t\t\t\t\t\t<sr7-bg id=\"SR7_16_1-8-10\" class=\"sr7-layer\"><noscript><img decoding=\"async\" src=\"https:\/\/www.replace-study.com\/wp-content\/uploads\/2020\/08\/globeheader.png\" alt=\"Globe Header\" title=\"Globe Header\"><\/noscript><\/sr7-bg>\n\t\t\t\t\t\t\t<sr7-txt id=\"SR7_16_1-8-2\" class=\"sr7-layer\"><strong>Racional<\/strong> y dise\u00f1o<\/sr7-txt>\n\t\t\t\t\t\t\t<p id=\"SR7_16_1-8-3\" class=\"sr7-layer\"><\/p>\n\t\t\t\t\t\t\t<sr7-txt id=\"SR7_16_1-8-9\" class=\"sr7-layer\"><i class=\"fa-quote-left\"><\/i> &nbsp; Los datos cl\u00ednicos indican que entre el 20%-60% de los pacientes con HAP que se encuentran recibiendo iPDE5 no logran alcanzar o mantener los objetivos de tratamiento <i class=\"fa-quote-right\"><\/i><br \/>\n<br \/>\n<\/sr7-txt>\n\t\t\t\t\t\t<\/sr7-slide>\n\t\t\t\t\t\t<sr7-slide id=\"SR7_16_1-21\" data-key=\"21\">\n\t\t\t\t\t\t<\/sr7-slide>\n\t\t\t\t\t<\/sr7-content>\n\t\t\t\t\t<image_lists style=\"display:none\">\n\t\t\t\t\t\t<img data-src=\"\/\/www.replace-study.com\/wp-content\/uploads\/2020\/08\/rightangle.png\" data-libid=\"96\" data-lib=\"medialibrary\" alt=\"Right Angle\" title=\"Right Angle\" width=\"0\" height=\"0\" data-dbsrc=\"Ly93d3cucmVwbGFjZS1zdHVkeS5jb20vd3AtY29udGVudC91cGxvYWRzLzIwMjAvMDgvcmlnaHRhbmdsZS5wbmc=\"\/>\n\t\t\t\t\t\t<img data-src=\"\/\/www.replace-study.com\/wp-content\/uploads\/2020\/08\/globeheader.png\" data-libid=\"97\" data-lib=\"medialibrary\" alt=\"Globe Header\" title=\"Globe Header\" width=\"0\" height=\"0\" data-dbsrc=\"Ly93d3cucmVwbGFjZS1zdHVkeS5jb20vd3AtY29udGVudC91cGxvYWRzLzIwMjAvMDgvZ2xvYmVoZWFkZXIucG5n\"\/>\n\t\t\t\t\t<\/image_lists>\n\t\t\t\t<\/sr7-module>\n\t\t\t\t<script>\n\t\t\t\t\twindow.SR7 ??={};SR7.PMH ??={}; SR7.PMH[\"SR7_16_1\"] = {cn:100,state:false,fn: function() { if (window._tpt!==undefined && window._tpt.prepareModuleHeight !== undefined) {  _tpt.prepareModuleHeight({id:\"SR7_16_1\",el:[400,400,400,300,180],type:'standard',shdw:'0',gh:[400,400,400,300,180],gw:[1240,1240,1024,778,480],vpt:['-200px&#039;,&#039;-200px&#039;,&#039;-200px&#039;,&#039;-200px&#039;,&#039;-200px'],size:{fullWidth:true, fullHeight:false},mh:'0',onh:0,onw:0,bg:{color:'{\"orig\":\"transparent\",\"type\":\"solid\",\"string\":\"transparent\"}'},plType:'0',plColor:'#FFFFFF'});   SR7.PMH[\"SR7_16_1\"].state=true;} else if(SR7.PMH[\"SR7_16_1\"].cn-->0)\tsetTimeout( SR7.PMH[\"SR7_16_1\"].fn,19);}};SR7.PMH[\"SR7_16_1\" ].fn();\n\t\t\t\t<\/script>\n<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-inner-section elementor-element elementor-element-31104ce8 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"31104ce8\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-50 elementor-inner-column elementor-element elementor-element-22deea15\" data-id=\"22deea15\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-435dd466 elementor-widget elementor-widget-heading\" data-id=\"435dd466\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Racional del estudio<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-3e7347ae elementor-widget elementor-widget-text-editor\" data-id=\"3e7347ae\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>Los datos cl\u00ednicos indican que entre el 20%-60% de los pacientes con <span id=\"su_tooltip_69ebe73cbb6e7_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbb6e7\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">HAP<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbb6e7\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">HAP, hipertensi\u00f3n arterial pulmonar<\/span><\/span><span id=\"su_tooltip_69ebe73cbb6e7_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> que se encuentran recibiendo <span id=\"su_tooltip_69ebe73cbb7b2_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbb7b2\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">iPDE5<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbb7b2\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">iPDE5, inhibidor de fosfodieterasa 5<\/span><\/span><span id=\"su_tooltip_69ebe73cbb7b2_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> no logran alcanzar o mantener los objetivos de tratamiento<sup>1, 2, 3<\/sup> . La progresi\u00f3n del tratamiento, incluyendo la terapia combinada, es una opci\u00f3n para estos pacientes<sup>4, 5<\/sup>; sin embargo, la terapia de combinaci\u00f3n puede tener efectos adversos adicionales<sup>6<\/sup>, asi como costos considerables. <sup>7, 8<\/sup><\/p>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t<div class=\"elementor-column elementor-col-50 elementor-inner-column elementor-element elementor-element-6b8a3bc\" data-id=\"6b8a3bc\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-2eede460 elementor-widget elementor-widget-html\" data-id=\"2eede460\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"html.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<svg xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"230\" height=\"200\" viewbox=\"0 0 149 101\" fill=\"none\">\n<path d=\"M143.6 33.5H84.9C82.4 33.5 80.3 31.4 80.3 28.9V9.99999C80.3 7.49999 82.4 5.39999 84.9 5.39999H143.7C146.2 5.39999 148.3 7.49999 148.3 9.99999V28.9C148.2 31.5 146.2 33.5 143.6 33.5Z\" fill=\"#B5DEF1\"><\/path>\n<path d=\"M143.6 94.8H84.9C82.4 94.8 80.3 92.7 80.3 90.2V71.3C80.3 68.8 82.4 66.7 84.9 66.7H143.7C146.2 66.7 148.3 68.8 148.3 71.3V90.2C148.2 92.8 146.2 94.8 143.6 94.8Z\" fill=\"#B5DEF1\"><\/path>\n<path d=\"M91.5001 39H65.3001C61.8001 39 58.9001 36.1 58.9001 32.6V6.4C58.9001 2.9 61.8001 0 65.3001 0H91.5001C95.0001 0 97.9001 2.9 97.9001 6.4V32.6C97.9001 36.1 95.0001 39 91.5001 39Z\" fill=\"#45ACDD\"><\/path>\n<path d=\"M91.5001 100.3H65.3001C61.8001 100.3 58.9001 97.4 58.9001 93.9V67.7C58.9001 64.2 61.8001 61.3 65.3001 61.3H91.5001C95.0001 61.3 97.9001 64.2 97.9001 67.7V93.9C97.9001 97.4 95.0001 100.3 91.5001 100.3Z\" fill=\"#45ACDD\"><\/path>\n<path d=\"M20.3 50.1H74.6C76.7 50.1 78.4001 52 78.4001 54.4V67.5M20.3 50.2H74.6C76.7 50.2 78.4001 48.3 78.4001 45.9V29.5\" stroke=\"#0C3549\" stroke-width=\"4\" stroke-miterlimit=\"10\" stroke-linecap=\"round\"><\/path>\n<path d=\"M74.8999 29.9L78.3999 26.8L81.8999 29.9M81.8999 69.2L78.3999 72.3L74.8999 69.2H81.8999Z\" stroke=\"#0C3549\" stroke-width=\"4\" stroke-miterlimit=\"10\" stroke-linecap=\"round\" stroke-linejoin=\"round\"><\/path>\n<path d=\"M34.6 69.6H8.4C4.9 69.6 2 66.7 2 63.2V37C2 33.5 4.9 30.6 8.4 30.6H34.6C38.1 30.6 41 33.5 41 37V63.2C41 66.7 38.1 69.6 34.6 69.6Z\" fill=\"#0791D2\"><\/path>\n<path d=\"M34.6 69.6H8.4C4.9 69.6 2 66.7 2 63.2V37C2 33.5 4.9 30.6 8.4 30.6H34.6C38.1 30.6 41 33.5 41 37V63.2C41 66.7 38.1 69.6 34.6 69.6Z\" stroke=\"#0C3549\" stroke-width=\"4\" stroke-miterlimit=\"10\" stroke-linecap=\"round\"><\/path>\n<\/svg>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-69f3dd81 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"69f3dd81\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-797730e5\" data-id=\"797730e5\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-4bd11542 elementor-widget elementor-widget-image\" data-id=\"4bd11542\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img fetchpriority=\"high\" decoding=\"async\" width=\"768\" height=\"487\" src=\"https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/Moa_v3_Spanish-768x487.jpg\" class=\"attachment-medium_large size-medium_large wp-image-1090\" alt=\"Moa_v3_Spanish\" srcset=\"https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/Moa_v3_Spanish-768x487.jpg 768w, https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/Moa_v3_Spanish-300x190.jpg 300w, https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/Moa_v3_Spanish-1024x649.jpg 1024w, https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/Moa_v3_Spanish-1536x973.jpg 1536w, https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/Moa_v3_Spanish-2048x1298.jpg 2048w\" sizes=\"(max-width: 768px) 100vw, 768px\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">El mecanismo de acci\u00f3n de riociguat<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-141865db elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"141865db\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-7f8c714c\" data-id=\"7f8c714c\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-1f4fa738 elementor-icon-list--layout-traditional elementor-list-item-link-full_width elementor-widget elementor-widget-icon-list\" data-id=\"1f4fa738\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"icon-list.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<ul class=\"elementor-icon-list-items\">\n\t\t\t\t\t\t\t<li class=\"elementor-icon-list-item\">\n\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-icon\">\n\t\t\t\t\t\t\t<i aria-hidden=\"true\" class=\"fas fa-check\"><\/i>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-text\">Riociguat, un estimulador de la <span id=\"su_tooltip_69ebe73cbb9f2_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbb9f2\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">GCs<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbb9f2\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">GCs, guanilato ciclasa soluble<\/span><\/span><span id=\"su_tooltip_69ebe73cbb9f2_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>, act\u00faa en la misma v\u00eda fisiopatol\u00f3gica que los <span id=\"su_tooltip_69ebe73cbbaaa_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbbaaa\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">iPDE5<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbbaaa\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">iPDE5, inhibidor de fosfodieterasa 5<\/span><\/span><span id=\"su_tooltip_69ebe73cbbaaa_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>, la v\u00eda del <span id=\"su_tooltip_69ebe73cbbb4d_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbbb4d\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">ON<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbbb4d\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">ON, \u00f3xido n\u00edtrico<\/span><\/span><span id=\"su_tooltip_69ebe73cbbb4d_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>-<span id=\"su_tooltip_69ebe73cbbbe4_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbbbe4\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">GCs<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbbbe4\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">GCs, guanilato ciclasa soluble<\/span><\/span><span id=\"su_tooltip_69ebe73cbbbe4_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>-<span id=\"su_tooltip_69ebe73cbbc73_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbbc73\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">GMPc<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbbc73\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">GMPc, guanos\u00edn monofosfato c\u00edclico<\/span><\/span><span id=\"su_tooltip_69ebe73cbbc73_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>, pero con un mecanismo de acci\u00f3n y un target molecular diferentes dentro de la misma v\u00eda.<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t<li class=\"elementor-icon-list-item\">\n\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-icon\">\n\t\t\t\t\t\t\t<i aria-hidden=\"true\" class=\"fas fa-check\"><\/i>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-text\">En sujetos sanos, la activaci\u00f3n de la <span id=\"su_tooltip_69ebe73cbbcd4_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbbcd4\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">GCs<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbbcd4\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">GCs, guanilato ciclasa soluble<\/span><\/span><span id=\"su_tooltip_69ebe73cbbcd4_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> por el <span id=\"su_tooltip_69ebe73cbbd2f_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbbd2f\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">ON<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbbd2f\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">ON, \u00f3xido n\u00edtrico<\/span><\/span><span id=\"su_tooltip_69ebe73cbbd2f_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> resulta en la s\u00edntesis de <span id=\"su_tooltip_69ebe73cbbda5_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbbda5\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">cGMP<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbbda5\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">GMPc, guanos\u00edn monofosfato c\u00edclico<\/span><\/span><span id=\"su_tooltip_69ebe73cbbda5_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> que produce vasodilataci\u00f3n en la circulaci\u00f3n pulmonar<sup>9<\/sup>. La PDE5 degrada el <span id=\"su_tooltip_69ebe73cbbe24_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbbe24\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">cGMP<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbbe24\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">GMPc, guanos\u00edn monofosfato c\u00edclico<\/span><\/span><span id=\"su_tooltip_69ebe73cbbe24_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>; por lo tanto, los <span id=\"su_tooltip_69ebe73cbbe7f_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbbe7f\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">iPDE5<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbbe7f\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">iPDE5, inhibidor de fosfodieterasa 5<\/span><\/span><span id=\"su_tooltip_69ebe73cbbe7f_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> aumentan los niveles intracelulares de <span id=\"su_tooltip_69ebe73cbbed5_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbbed5\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">cGMP<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbbed5\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">GMPc, guanos\u00edn monofosfato c\u00edclico<\/span><\/span><span id=\"su_tooltip_69ebe73cbbed5_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> levels.<sup>9  <\/sup><\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t<li class=\"elementor-icon-list-item\">\n\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-icon\">\n\t\t\t\t\t\t\t<i aria-hidden=\"true\" class=\"fas fa-check\"><\/i>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-text\">Sin embargo, en pacientes con <span id=\"su_tooltip_69ebe73cbbf28_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbbf28\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">HAP<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbbf28\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">HAP, hipertensi\u00f3n arterial pulmonar<\/span><\/span><span id=\"su_tooltip_69ebe73cbbf28_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>, la biodisponibilidad de <span id=\"su_tooltip_69ebe73cbbf79_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbbf79\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">ON<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbbf79\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">ON, \u00f3xido n\u00edtrico<\/span><\/span><span id=\"su_tooltip_69ebe73cbbf79_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> esta disminuida ,<sup>10, 11, 12, 13, 14<\/sup> lo que puede hacer que los <span id=\"su_tooltip_69ebe73cbbfcb_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbbfcb\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">iPDE5<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbbfcb\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">iPDE5, inhibidor de fosfodieterasa 5<\/span><\/span><span id=\"su_tooltip_69ebe73cbbfcb_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> sean inefectivos. A diferencia de los <span id=\"su_tooltip_69ebe73cbc01d_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc01d\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">iPDE5<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc01d\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">iPDE5, inhibidor de fosfodieterasa 5<\/span><\/span><span id=\"su_tooltip_69ebe73cbc01d_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>, riociguat estimula directamente la <span id=\"su_tooltip_69ebe73cbc096_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc096\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">GCs<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc096\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">GCs, guanilato ciclasa soluble<\/span><\/span><span id=\"su_tooltip_69ebe73cbc096_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>, aumentando los niveles intracelulares de <span id=\"su_tooltip_69ebe73cbc13c_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc13c\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">GMPc<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc13c\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">GMPc, guanos\u00edn monofosfato c\u00edclico<\/span><\/span><span id=\"su_tooltip_69ebe73cbc13c_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> independientemente del <span id=\"su_tooltip_69ebe73cbc1b8_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc1b8\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">ON<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc1b8\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">ON, \u00f3xido n\u00edtrico<\/span><\/span><span id=\"su_tooltip_69ebe73cbc1b8_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>.<sup>15, 16<\/sup> <\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t<li class=\"elementor-icon-list-item\">\n\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-icon\">\n\t\t\t\t\t\t\t<i aria-hidden=\"true\" class=\"fas fa-check\"><\/i>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-text\">Riociguat puede por lo tanto ser efectivo en pacientes con <span id=\"su_tooltip_69ebe73cbc213_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc213\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">HAP<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc213\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">HAP, hipertensi\u00f3n arterial pulmonar<\/span><\/span><span id=\"su_tooltip_69ebe73cbc213_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> que no responden adecuadamente a los <span id=\"su_tooltip_69ebe73cbc287_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc287\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">iPDE5<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc287\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">iPDE5, inhibidor de fosfodieterasa 5<\/span><\/span><span id=\"su_tooltip_69ebe73cbc287_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> a trav\u00e9s de la optimizaci\u00f3n de la v\u00eda del <span id=\"su_tooltip_69ebe73cbc2dc_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc2dc\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">ON<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc2dc\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">ON, \u00f3xido n\u00edtrico<\/span><\/span><span id=\"su_tooltip_69ebe73cbc2dc_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>-<span id=\"su_tooltip_69ebe73cbc32d_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc32d\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">GCs<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc32d\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">GCs, guanilato ciclasa soluble<\/span><\/span><span id=\"su_tooltip_69ebe73cbc32d_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>-<span id=\"su_tooltip_69ebe73cbc37c_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc37c\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">GMPc<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc37c\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">GMPc, guanos\u00edn monofosfato c\u00edclico<\/span><\/span><span id=\"su_tooltip_69ebe73cbc37c_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>.<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t<li class=\"elementor-icon-list-item\">\n\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-icon\">\n\t\t\t\t\t\t\t<i aria-hidden=\"true\" class=\"fas fa-check\"><\/i>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-text\">El estudio piloto, abierto y no controlado RESPITE evalu\u00f3 el cambio de f\u00e1rmacos que act\u00faan dentro de la misma v\u00eda. <sup>17<\/sup> El cambio a riociguat se asoci\u00f3 con mejor\u00edas desde la basal en la <span id=\"su_tooltip_69ebe73cbc3cb_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc3cb\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">6MWD<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc3cb\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">6MWD, distancia recorrida en el test de marcha de 6 minutos<\/span><\/span><span id=\"su_tooltip_69ebe73cbc3cb_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>, <span id=\"su_tooltip_69ebe73cbc426_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc426\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">NT-proBNP<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc426\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">NT-proBNP, prohormona N-terminal del p\u00e9pitdo natriur\u00e9tico cerebral<\/span><\/span><span id=\"su_tooltip_69ebe73cbc426_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>, y <span id=\"su_tooltip_69ebe73cbc479_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc479\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">CF OMS<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc479\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">CF OMS, clase funcional de la Organizaci\u00f3n Mundial de la Salud<\/span><\/span><span id=\"su_tooltip_69ebe73cbc479_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>.<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t<li class=\"elementor-icon-list-item\">\n\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-icon\">\n\t\t\t\t\t\t\t<i aria-hidden=\"true\" class=\"fas fa-check\"><\/i>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-text\">Dado las se\u00f1ales positivas observadas en RESPITE, se requerian m\u00e1s datos para confirmar que los pacientes con <span id=\"su_tooltip_69ebe73cbc4c8_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc4c8\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">HAP<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc4c8\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">HAP, hipertensi\u00f3n arterial pulmonar<\/span><\/span><span id=\"su_tooltip_69ebe73cbc4c8_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> en tratamiento estable con <span id=\"su_tooltip_69ebe73cbc518_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc518\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">iPDE5<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc518\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">iPDE5, inhibidor de fosfodieterasa 5<\/span><\/span><span id=\"su_tooltip_69ebe73cbc518_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> pero que no alcanzan objetivos de tratamiento pueden alcanzar mejor\u00eda cl\u00ednica cambiando el <span id=\"su_tooltip_69ebe73cbc592_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc592\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">iPDE5<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc592\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">iPDE5, inhibidor de fosfodieterasa 5<\/span><\/span><span id=\"su_tooltip_69ebe73cbc592_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> a riociguat.<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t<li class=\"elementor-icon-list-item\">\n\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-icon\">\n\t\t\t\t\t\t\t<i aria-hidden=\"true\" class=\"fas fa-check\"><\/i>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-text\">El estudio prospectivo, randomizado y controlado REPLACE evalu\u00f3 la eficacia y seguridad de cambiar un <span id=\"su_tooltip_69ebe73cbc5ff_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc5ff\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">iPDE5<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc5ff\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">iPDE5, inhibidor de fosfodieterasa 5<\/span><\/span><span id=\"su_tooltip_69ebe73cbc5ff_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> (\u00b1<span id=\"su_tooltip_69ebe73cbc653_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc653\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">ERA<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc653\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">ERA, antagonista de receptor de endotelina<\/span><\/span><span id=\"su_tooltip_69ebe73cbc653_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> de base) comparado con permanecer con <span id=\"su_tooltip_69ebe73cbc6a3_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbc6a3\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">iPDE5<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbc6a3\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">iPDE5, inhibidor de fosfodieterasa 5<\/span><\/span><span id=\"su_tooltip_69ebe73cbc6a3_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>.<sup>18<\/sup><\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t<\/ul>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-77a6c96 elementor-section-stretched elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"77a6c96\" data-element_type=\"section\" data-e-type=\"section\" data-settings=\"{&quot;stretch_section&quot;:&quot;section-stretched&quot;,&quot;background_background&quot;:&quot;classic&quot;}\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-31e991eb\" data-id=\"31e991eb\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-5e26b4ac elementor-widget elementor-widget-spacer\" data-id=\"5e26b4ac\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<section class=\"elementor-section elementor-inner-section elementor-element elementor-element-457fd503 elementor-section-content-middle elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"457fd503\" data-element_type=\"section\" data-e-type=\"section\" data-settings=\"{&quot;background_background&quot;:&quot;classic&quot;}\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-inner-column elementor-element elementor-element-787f3a5e\" data-id=\"787f3a5e\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-2ec22634 elementor-widget elementor-widget-text-editor\" data-id=\"2ec22634\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p><center>Estudio prospectivo, randomizado, internacional, multic\u00e9ntrico, de dos ramas, controlado, a 24 semanas, abierto, de fase IV, evaluando el efecto de cambiar a riociguat comparado con mantener un <span id=\"su_tooltip_69ebe73cbcd39_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbcd39\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">iPDE5<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbcd39\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">iPDE5, inhibidor de fosfodieterasa 5<\/span><\/span><span id=\"su_tooltip_69ebe73cbcd39_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> en pacientes con <span id=\"su_tooltip_69ebe73cbcdc3_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbcdc3\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">HAP<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbcdc3\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">HAP, hipertensi\u00f3n arterial pulmonar<\/span><\/span><span id=\"su_tooltip_69ebe73cbcdc3_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> en riesgo intermedio.<\/center><\/p>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-inner-section elementor-element elementor-element-4c59c588 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"4c59c588\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-inner-column elementor-element elementor-element-3e189887\" data-id=\"3e189887\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-686a95ef elementor-hidden-tablet elementor-hidden-phone elementor-widget elementor-widget-image\" data-id=\"686a95ef\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"1078\" height=\"280\" src=\"https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/03\/Rationale_Study-design_Spanish_Ali-1.jpg\" class=\"attachment-full size-full wp-image-1262\" alt=\"Rationale_Study-design_Spanish\" srcset=\"https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/03\/Rationale_Study-design_Spanish_Ali-1.jpg 1078w, https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/03\/Rationale_Study-design_Spanish_Ali-1-300x78.jpg 300w, https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/03\/Rationale_Study-design_Spanish_Ali-1-1024x266.jpg 1024w, https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/03\/Rationale_Study-design_Spanish_Ali-1-768x199.jpg 768w\" sizes=\"(max-width: 1078px) 100vw, 1078px\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-84e0fad elementor-hidden-desktop elementor-widget elementor-widget-image\" data-id=\"84e0fad\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"892\" height=\"934\" src=\"https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/Study-design-Mobile.png\" class=\"attachment-large size-large wp-image-1013\" alt=\"\" srcset=\"https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/Study-design-Mobile.png 892w, https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/Study-design-Mobile-287x300.png 287w, https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/Study-design-Mobile-768x804.png 768w\" sizes=\"(max-width: 892px) 100vw, 892px\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-4b0ae319 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"4b0ae319\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-33 elementor-top-column elementor-element elementor-element-20541749\" data-id=\"20541749\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-6d5f50c9 elementor-widget elementor-widget-heading\" data-id=\"6d5f50c9\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Poblaci\u00f3n de pacientes<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-233de911 elementor-widget elementor-widget-text-editor\" data-id=\"233de911\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p class=\"p1\">Pacientes tratados con dosis estables de <span id=\"su_tooltip_69ebe73cbd520_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbd520\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">iPDE5<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbd520\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">iPDE5, inhibidor de fosfodieterasa 5<\/span><\/span><span id=\"su_tooltip_69ebe73cbd520_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span>\u00b1<span id=\"su_tooltip_69ebe73cbd5cb_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbd5cb\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">ERA<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbd5cb\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">ERA, antagonista de receptor de endotelina<\/span><\/span><span id=\"su_tooltip_69ebe73cbd5cb_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> por 5 semanas, en riesgo intemedio.<\/p>\n<p class=\"p1\">Riesgo intermedio, definido por:<\/p>\n<ul class=\"ul1\">\n<li class=\"li1\"><span id=\"su_tooltip_69ebe73cbd657_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbd657\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">CF OMS<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbd657\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">CF OMS, clase funcional de la Organizaci\u00f3n Mundial de la Salud<\/span><\/span><span id=\"su_tooltip_69ebe73cbd657_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> III<\/li>\n<li class=\"li1\"><span id=\"su_tooltip_69ebe73cbd6be_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbd6be\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">6MWD<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbd6be\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">6MWD, distancia recorrida en el test de marcha de 6 minutos<\/span><\/span><span id=\"su_tooltip_69ebe73cbd6be_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> 165-440 m<\/li>\n<\/ul>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t<div class=\"elementor-column elementor-col-33 elementor-top-column elementor-element elementor-element-2a5d536f\" data-id=\"2a5d536f\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap\">\n\t\t\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t<div class=\"elementor-column elementor-col-33 elementor-top-column elementor-element elementor-element-7595a265\" data-id=\"7595a265\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-473b4aed elementor-widget elementor-widget-heading\" data-id=\"473b4aed\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Endpoint primario (adjudicaci\u00f3n central)<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-685fd69 elementor-widget elementor-widget-text-editor\" data-id=\"685fd69\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<ul>\n<li class=\"p1\">Mejor\u00eda cl\u00ednica a la semana 24, definida por 2 de 3:\n<ul>\n<li>Aumento de <span id=\"su_tooltip_69ebe73cbdd1d_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbdd1d\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">6MWD<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbdd1d\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">6MWD, distancia recorrida en el test de marcha de 6 minutos<\/span><\/span><span id=\"su_tooltip_69ebe73cbdd1d_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> en \u2265 10% o \u2265 30 m<\/li>\n<li><span id=\"su_tooltip_69ebe73cbdd99_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbdd99\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">CF OMS<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbdd99\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">CF OMS, clase funcional de la Organizaci\u00f3n Mundial de la Salud<\/span><\/span><span id=\"su_tooltip_69ebe73cbdd99_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> I\/II<\/li>\n<li>Disminuci\u00f3n del <span id=\"su_tooltip_69ebe73cbde08_button\" class=\"su-tooltip-button su-tooltip-button-outline-yes tool\" aria-describedby=\"su_tooltip_69ebe73cbde08\" data-settings='{\"position\":\"top\",\"behavior\":\"hover\",\"hideDelay\":0}' tabindex=\"0\">NT-proBNP<\/span><span style=\"display:none;z-index:100\" id=\"su_tooltip_69ebe73cbde08\" class=\"su-tooltip tool\" role=\"tooltip\"><span class=\"su-tooltip-inner su-tooltip-shadow-no\" style=\"z-index:100;background:#505050;color:#F3F3F3;font-size:14px;border-radius:0px;text-align:left;max-width:300px;line-height:1.25\"><span class=\"su-tooltip-title\"><\/span><span class=\"su-tooltip-content su-u-trim\">NT-proBNP, prohormona N-terminal del p\u00e9pitdo natriur\u00e9tico cerebral<\/span><\/span><span id=\"su_tooltip_69ebe73cbde08_arrow\" class=\"su-tooltip-arrow\" style=\"z-index:100;background:#505050\" data-popper-arrow><\/span><\/span> en \u2265 30%<\/li>\n<\/ul>\n<\/li>\n<li>Ausencia de deterioro cl\u00ednico<\/li>\n<\/ul>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-4c5652da elementor-section-stretched elementor-section-full_width elementor-section-height-default elementor-section-height-default\" data-id=\"4c5652da\" data-element_type=\"section\" data-e-type=\"section\" data-settings=\"{&quot;stretch_section&quot;:&quot;section-stretched&quot;,&quot;background_background&quot;:&quot;classic&quot;}\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-51526c2b\" data-id=\"51526c2b\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-inner-section elementor-element elementor-element-701e76c9 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"701e76c9\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-50 elementor-inner-column elementor-element elementor-element-21e7ab01\" data-id=\"21e7ab01\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-6c40a47b elementor-widget elementor-widget-heading\" data-id=\"6c40a47b\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Centros del estudio<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-5ab52416 elementor-widget elementor-widget-text-editor\" data-id=\"5ab52416\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>El estudio REPLACE fue conducido en 81 centros en 22 pa\u00edses<\/p>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t<div class=\"elementor-column elementor-col-50 elementor-inner-column elementor-element elementor-element-26fdf38b\" data-id=\"26fdf38b\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-686d8e41 elementor-widget elementor-widget-shortcode\" data-id=\"686d8e41\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"shortcode.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-shortcode\">[interactive-map]<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-64d5ded elementor-section-stretched elementor-section-full_width elementor-section-height-default elementor-section-height-default\" data-id=\"64d5ded\" data-element_type=\"section\" data-e-type=\"section\" data-settings=\"{&quot;stretch_section&quot;:&quot;section-stretched&quot;,&quot;background_background&quot;:&quot;classic&quot;}\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-ac5763\" data-id=\"ac5763\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-inner-section elementor-element elementor-element-389b9e60 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"389b9e60\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-33 elementor-inner-column elementor-element elementor-element-4b4051c8\" data-id=\"4b4051c8\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-4abbe5ce elementor-widget elementor-widget-heading\" data-id=\"4abbe5ce\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Resumen del estudio<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-3873e664 elementor-widget__width-initial elementor-widget elementor-widget-video\" data-id=\"3873e664\" data-element_type=\"widget\" data-e-type=\"widget\" data-settings=\"{&quot;video_type&quot;:&quot;hosted&quot;,&quot;show_image_overlay&quot;:&quot;yes&quot;,&quot;image_overlay&quot;:{&quot;url&quot;:&quot;http:\\\/\\\/localhost\\\/replace\\\/wp-content\\\/uploads\\\/2021\\\/02\\\/Thumbnail.png&quot;,&quot;id&quot;:1014,&quot;size&quot;:&quot;&quot;},&quot;lightbox&quot;:&quot;yes&quot;,&quot;controls&quot;:&quot;yes&quot;}\" data-widget_type=\"video.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"e-hosted-video elementor-wrapper elementor-open-lightbox\">\n\t\t\t\t\t\t\t<div class=\"elementor-custom-embed-image-overlay\" data-elementor-open-lightbox=\"yes\" data-elementor-lightbox=\"{&quot;type&quot;:&quot;video&quot;,&quot;videoType&quot;:&quot;hosted&quot;,&quot;url&quot;:&quot;https:\\\/\\\/www.replace-study.com\\\/wp-content\\\/uploads\\\/videos\\\/REPLACE-study-design.mp4&quot;,&quot;autoplay&quot;:&quot;&quot;,&quot;modalOptions&quot;:{&quot;id&quot;:&quot;elementor-lightbox-3873e664&quot;,&quot;entranceAnimation&quot;:&quot;&quot;,&quot;entranceAnimation_tablet&quot;:&quot;&quot;,&quot;entranceAnimation_mobile&quot;:&quot;&quot;,&quot;videoAspectRatio&quot;:&quot;169&quot;},&quot;videoParams&quot;:{&quot;controls&quot;:&quot;&quot;,&quot;preload&quot;:&quot;metadata&quot;,&quot;controlsList&quot;:&quot;nodownload&quot;}}\" data-e-action-hash=\"#elementor-action%3Aaction%3Dlightbox%26settings%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%3D%3D\">\n\t\t\t\t\t\t\t\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"500\" height=\"281\" src=\"https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/Thumbnail.png\" class=\"attachment-large size-large wp-image-1014\" alt=\"\" srcset=\"https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/Thumbnail.png 500w, https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/Thumbnail-300x169.png 300w\" sizes=\"(max-width: 500px) 100vw, 500px\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<div class=\"elementor-custom-embed-play\" role=\"button\" aria-label=\"Reproducir v\u00eddeo\" tabindex=\"0\">\n\t\t\t\t\t\t\t<i aria-hidden=\"true\" class=\"eicon-play\"><\/i>\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-124bad0b elementor-widget elementor-widget-text-editor\" data-id=\"124bad0b\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>El profesor Marius Hoeper presenta el dise\u00f1o del estudio y su racional<\/p>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-56aae501 elementor-hidden-phone elementor-widget elementor-widget-spacer\" data-id=\"56aae501\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-e6222d9 elementor-align-center wplightbox elementor-widget elementor-widget-button\" data-id=\"e6222d9\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"button.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<div class=\"elementor-button-wrapper\">\n\t\t\t\t\t<a class=\"elementor-button elementor-button-link elementor-size-sm\" href=\"https:\/\/www.replace-study.com\/wp-content\/uploads\/videos\/REPLACE-study-design_es.mp4\">\n\t\t\t\t\t\t<span class=\"elementor-button-content-wrapper\">\n\t\t\t\t\t\t<span class=\"elementor-button-icon\">\n\t\t\t\t<i aria-hidden=\"true\" class=\"fas fa-angle-right\"><\/i>\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t<span class=\"elementor-button-text\">Reproducir el video<\/span>\n\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/a>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t<div class=\"elementor-column elementor-col-33 elementor-inner-column elementor-element elementor-element-76313387\" data-id=\"76313387\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-407603a9 elementor-widget elementor-widget-heading\" data-id=\"407603a9\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Resultados del estudio<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-51edf6a2 elementor-widget elementor-widget-image\" data-id=\"51edf6a2\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"210\" height=\"140\" src=\"https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/studyresults.png\" class=\"attachment-large size-large wp-image-986\" alt=\"\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-30f809d9 elementor-widget elementor-widget-text-editor\" data-id=\"30f809d9\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>Vea la presentaci\u00f3n de los resultados del estudio y datos de soporte<\/p>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-2ce7106d elementor-hidden-phone elementor-widget elementor-widget-spacer\" data-id=\"2ce7106d\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-40111878 elementor-align-center elementor-widget elementor-widget-button\" data-id=\"40111878\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"button.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<div class=\"elementor-button-wrapper\">\n\t\t\t\t\t<a class=\"elementor-button elementor-button-link elementor-size-sm\" href=\"https:\/\/www.replace-study.com\/es\/resultados-del-estudio\/\">\n\t\t\t\t\t\t<span class=\"elementor-button-content-wrapper\">\n\t\t\t\t\t\t<span class=\"elementor-button-icon\">\n\t\t\t\t<i aria-hidden=\"true\" class=\"fas fa-angle-right\"><\/i>\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t<span class=\"elementor-button-text\">Conozca m\u00e1s<\/span>\n\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/a>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t<div class=\"elementor-column elementor-col-33 elementor-inner-column elementor-element elementor-element-77999d34\" data-id=\"77999d34\" data-element_type=\"column\" data-e-type=\"column\" data-settings=\"{&quot;background_background&quot;:&quot;classic&quot;}\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-31837854 elementor-widget elementor-widget-heading\" data-id=\"31837854\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Bibliograf\u00eda<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-73a8bd74 elementor-widget elementor-widget-image\" data-id=\"73a8bd74\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img loading=\"lazy\" decoding=\"async\" width=\"210\" height=\"140\" src=\"https:\/\/www.replace-study.com\/wp-content\/uploads\/2021\/02\/resources.png\" class=\"attachment-large size-large wp-image-988\" alt=\"\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-68806f48 elementor-widget elementor-widget-text-editor\" data-id=\"68806f48\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>Encuentre bibliograf\u00eda asociada con el estudio, incluyendo otras publicaciones de riociguat<\/p>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-35d49a9b elementor-widget elementor-widget-spacer\" data-id=\"35d49a9b\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-6fab29a4 elementor-align-center elementor-widget elementor-widget-button\" data-id=\"6fab29a4\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"button.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<div class=\"elementor-button-wrapper\">\n\t\t\t\t\t<a class=\"elementor-button elementor-button-link elementor-size-sm\" href=\"https:\/\/www.replace-study.com\/es\/bibliografia\/\">\n\t\t\t\t\t\t<span class=\"elementor-button-content-wrapper\">\n\t\t\t\t\t\t<span class=\"elementor-button-icon\">\n\t\t\t\t<i aria-hidden=\"true\" class=\"fas fa-angle-right\"><\/i>\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t<span class=\"elementor-button-text\">Conozca m\u00e1s<\/span>\n\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/a>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-4150d241 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"4150d241\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-5b58611a\" data-id=\"5b58611a\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-30762b93 elementor-widget elementor-widget-accordion\" data-id=\"30762b93\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"accordion.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-accordion\">\n\t\t\t\t\t\t\t<div class=\"elementor-accordion-item\">\n\t\t\t\t\t<div id=\"elementor-tab-title-8131\" class=\"elementor-tab-title\" data-tab=\"1\" role=\"button\" aria-controls=\"elementor-tab-content-8131\" aria-expanded=\"false\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-accordion-icon elementor-accordion-icon-right\" aria-hidden=\"true\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-accordion-icon-closed\"><i class=\"fas fa-chevron-down\"><\/i><\/span>\n\t\t\t\t\t\t\t\t<span class=\"elementor-accordion-icon-opened\"><i class=\"fas fa-chevron-up\"><\/i><\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-accordion-title\" tabindex=\"0\">Bibliograf\u00eda<\/a>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t<div id=\"elementor-tab-content-8131\" class=\"elementor-tab-content elementor-clearfix\" data-tab=\"1\" role=\"region\" aria-labelledby=\"elementor-tab-title-8131\"><ol>\n<li>Chockalingam A et al. Int J Cardiol 2005;99:91\u201395.<\/li>\n<li>Leuchte HH et al. Chest 2004;125:580\u2013586.<\/li>\n<li>Gali\u00e8 N et al. N Engl J Med 2015;373:834\u2013844.<\/li>\n<li>Gali\u00e8 N et al. Eur Respir J 2015;46:903\u2013975.<\/li>\n<li>Lajoie AC et al. Lancet Respir Med 2016;4:291\u2013305.<\/li>\n<li>Liu HL et al. Chest 2016;150:353\u2013366.<\/li>\n<li>Hill NS et al. J Manag Care Spec Pharm 2016;22:S3\u2013S21.<\/li>\n<li>Wilkens H et al. Respir Med 2010;104:902\u2013910.<\/li>\n<li>Ghofrani HA et al. Nat Rev Drug Discov 2006;5:689\u2013702.<\/li>\n<li>Archer SL et al. Am J Respir Crit Care Med 1998;158:1061\u20131067.<\/li>\n<li>Giaid A and Saleh S. N Engl J Med 1995;333:214\u2013221.<\/li>\n<li>Kielsten JT et al. Arterioscler Thromb Vasc Biol 2005;25:1414\u20131418.<\/li>\n<li>Migneault A et al. Am J Respir Crit Care Med 2005;171:506\u2013513.<\/li>\n<li>Tsai EJ and Kass DA. Pharmcol Ther 2009;122:216\u2013238.<\/li>\n<li>Stasch JP et al. Nature 2001;410:212\u2013215.<\/li>\n<li>Stasch JP et al. Circulation 2011;123:2263\u20132273.<\/li>\n<li>Hoeper MM et al. Eur Respir J 2017;50:1602425.<\/li>\n<li>Hoeper, M. M et al. Am J Respir Crit Care Med 195: A2296.<\/li>\n<\/ol>\n<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-730050cf elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"730050cf\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-67acf961\" data-id=\"67acf961\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-e5010a3 elementor-hidden-desktop elementor-hidden-tablet elementor-hidden-phone elementor-widget elementor-widget-html\" data-id=\"e5010a3\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"html.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<style>.tool{\ntext-decoration:underline;\ntext-decoration-style: dotted;\ntext-decoration-color: #0791D2;\ntext-underline-position: under;\ncursor: pointer\n    }\n<\/style><script> \njQuery(document).ready(function($) { \nvar delay = 100; setTimeout(function() { \n$('.elementor-tab-title').removeClass('elementor-active');\n $('.elementor-tab-content').css('display', 'none'); }, delay); \n}); \n<\/script>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>Racional del estudio Los datos cl\u00ednicos indican que entre el 20%-60% de los pacientes con que se encuentran recibiendo no logran alcanzar o mantener los objetivos de tratamiento1, 2, 3 . La progresi\u00f3n del tratamiento, incluyendo la terapia combinada, es una opci\u00f3n para estos pacientes4, 5; sin embargo, la terapia de combinaci\u00f3n puede tener efectos &#8230; <a title=\"Racional y dise\u00f1o\" class=\"read-more\" href=\"https:\/\/www.replace-study.com\/es\/racional-y-diseno\/\" aria-label=\"Leer m\u00e1s sobre Racional y dise\u00f1o\">Leer m\u00e1s<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-1088","page","type-page","status-publish"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Racional y dise\u00f1o - The REPLACE study<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.replace-study.com\/es\/study-rationale-and-design\/\" \/>\n<meta property=\"og:locale\" content=\"es_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Racional y dise\u00f1o - The REPLACE study\" \/>\n<meta property=\"og:description\" content=\"Racional del estudio Los datos cl\u00ednicos indican que entre el 20%-60% de los pacientes con que se encuentran recibiendo no logran alcanzar o mantener los objetivos de tratamiento1, 2, 3 . La progresi\u00f3n del tratamiento, incluyendo la terapia combinada, es una opci\u00f3n para estos pacientes4, 5; sin embargo, la terapia de combinaci\u00f3n puede tener efectos ... 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