Editorial
Pharmacotherapy Impacts on COPD Mortality
La farmacoterapia tiene impacto en la mortalidad de la EPOC
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An Early Marker of Future COPD?" 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This editorial reviews what do these patients die from, the relevance of exacerbations or “chest attacks” on patient's outcomes and whether pharmacotherapy impacts on COPD mortality.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Dying From or With COPD</span><p id="par0010" class="elsevierStylePara elsevierViewall">Divo and coworkers<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a> have shown that COPD patients develop specific comorbidities that independently increase the risk of death, particularly coronary artery disease and lung cancer, which are the big mortality drivers in milder stages of COPD. This should direct health care providers to search for these diseases and manage them appropriately. The implementation of CT screening for lung cancer is one such measure that helps increase resectable tumor detection.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> As the severity of airflow limitation increases, the causes of death shift toward more respiratory causes, including pneumonia and respiratory insufficiency. In these patients, evaluation of lung function with lung volumes, functional capacity with the 6<span class="elsevierStyleHsp" style=""></span>min walk distance, oximetry and/or arterial blood gases can help detect individuals who may benefit from pulmonary rehabilitation, supplemental oxygen or non-invasive mechanical ventilation.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Exacerbation or the “Chest Attack”</span><p id="par0015" class="elsevierStylePara elsevierViewall">Exacerbations or “Chest Attacks” are crucial events in the natural course of COPD. Although they can occur at any severity stage, their impact increases as patients develop more severe airflow limitation. Soler-Cataluna et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a> first described the relationship between the presence and frequency of exacerbations with mortality. We now know that the first event increases the tempo and severity of subsequent events that impact on patient's outcomes. This was shown by Cote and co-workers<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> who followed 205 patients over 2 years and observed that the BODE index (a surrogate marker of increased mortality risk) in patients who exacerbated, increased after the attacks and did not return to normal during the observation period. This was confirmed by Kunisaki et al. in a trial of over 16 thousand patients.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> The authors found that the hazard ratio (HR) for cardiovascular events was increased, particularly in the first 30 days after the attack (HR, 3.8; 95% CI, 2.7–5.5). The 30-day HR after a hospitalization for the episode was more than twofold greater (HR, 9.9; 95% CI, 6.6–14.9). The numbers of cardiovascular events occurring after the exacerbations suggests some vascular dysfunction leading to myocardial infarction, stroke and pulmonary embolism. It is clear that prevention of exacerbations is an important goal of therapy, if we are to decrease mortality in COPD. It may not be wise to wait for exacerbations to occur in order to begin prevention. In an analogy to coronary artery disease, it makes no sense to wait for the first heart attack before starting therapy for the disease. In this context, every effort has to be made to help patients stop smoking, institute appropriate vaccinations and maintain a healthy exercise program because all of these decrease exacerbations risk.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Pharmacotherapy and Mortality</span><p id="par0020" class="elsevierStylePara elsevierViewall">The results of several large trials prove that pharmacotherapy reduces the risk of death in COPD. Let us start with the TORCH study, which randomized over 6000 patients for 3 years to four therapeutic arms; the active arm combined twice daily fluticasone proprionate/salmeterol (an ICS/LABA) and compared it with placebo, with two complementary arms corresponding to the individual components.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">7</span></a> There was a 17.5% relative risk reduction of mortality in the active arm compared with placebo, but the adjusted <span class="elsevierStyleItalic">P</span> value (due to an interim analysis that forced the statistical adjustment) was .052 and the study was unjustifiably seen as negative (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The subsequent SUMMIT trial that included over 16 thousand patients with moderate COPD (>60% predicted FEV1) randomized them to either once daily fluticasone furoate/vilanterol (ICS/LABA) or placebo and two arms that included the individual components.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">8</span></a> In this study, there was a 12% relative reduction in mortality risk between the active arm and the placebo (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.137) and the results were again considered negative. There have been other studies with mortality included as a secondary outcome that further support the argument that pharmacotherapy decreases risk of death. The first was the 4 year UPLIFT trial, which recruited over 6000 patients randomized to receive the once daily LAMA tiotropium versus placebo.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a> A statistical significance was observed at the end of the protocol-defined treatment period (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.034) but not 30 days thereafter (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.086). The hazard ratios for lower respiratory and cardiac mortality during treatment were 0.86 (95% CI 0.68–1.09) and 0.86 (95% CI 0.75–0.99) respectively. Another smaller study, the INSPIRE trial compared fluticasone Propionate/Salmeterol with Tiotropium and reported a 53% relative reduction in favor of the ICS/LABA.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">10</span></a> More recently, a stratified safety pooled analysis of all fatal events was performed comparing extrafine ICS-containing combinations versus ICS-free treatments in three 52-week studies (Tribute, Trinity and Trilogy).<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">11</span></a> The comparisons included, triple with beclomethasone/formoterol/glycopyrronium compared with tiotropium, the same versus a combination of indacaterol/glycopyrronium and another with beclomethasone/formoterol. The analysis showed a reduction in the risk of death with a HR of 0.71 (95% CI 0.50–1.02; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.066). Finally, the results of the IMPACT trial further supported this benefit.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">12</span></a> This 10,000 patients study compared triple therapy including fluticasone furoate/vilanterol/umeclidinium (ICS/LABA/LAMA) once daily, to one arm containing the same ICS/LABA and another the same LABA/LAMA. At study's end there was a relative risk reduction of death of 42% between the triple therapy and the LABA/LAMA combination and of 39% between the ICS/LABA and the LABA/LAMA. There was a non-significant relative reduction of 10.3% between triple and ICS/LABA. In the same studies, there were improvements in lung function, dyspnea, health status and exacerbations, including hospitalizations.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">With this evidence, it is not justified to maintain a nihilistic attitude about the effectiveness of the pharmacological agents currently available to our patients. Perhaps the decline in COPD deaths worldwide, is not only the consequence of altered smoking habits, but also of the judicious use of pharmacotherapy.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Dying From or With COPD" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Exacerbation or the “Chest Attack”" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Pharmacotherapy and Mortality" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">FP: fluticasone propionate; S: salmeterol. BDP: beclometasone dipropionate; FF: formoterol fumarate; G: glycopyrronium; TIO: tiotropium; IND: indacaterol; GB: glycopyrronium bromide; FFur: fluticasone furoate; VI: vilanterol UME: umeclidinium.</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">TORCH, Toward a Revolution in COPD Health.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">UPLIFT, Understanding Potential Long-Term Impacts on Function with Tiotropium.</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">INSPIRE, Investigating New Standards for Prophylaxis in Reducing Exacerbations.</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">SUMMIT, Study to Understand Mortality and Morbidity in COPD.</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">IMPACT, Informing the Pathway of COPD Treatment.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of Patients \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comparators \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR and 95% CIActive Versus Reference \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Relative Risk Reduction \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> Value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TORCH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6112 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FP/SversusPlacebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.83 (0.68,1.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.052 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UPLIFT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5993 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TiotropiumversusPlacebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.84 (0.73–0.97) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.038 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">INSPIRE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1323 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FP/SversusTiotropium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.48 (0.27,0.85) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.012 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SUMMIT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16,590 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FFur/VIversusPlacebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.88 (0.73,1.04) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.134 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TRINITY \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5589 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BDP/FF/G, BDP/FF, BDP/FF<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>TIO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.71 (0.50,1.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.066 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TRIBUTE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">versus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TRILOGY \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TIO, IND/GB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4372 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BDP/FF/GversusTIO, IND/GB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.72 (0.49,1.06) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.096 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IMPACT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10,355 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FFur/VI/UMEversusVI/UME \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.71 (0.51,0.99) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28.6% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.043 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2511111.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Summary of Results of Randomized Trials of Different Inhaled Therapies Where All-cause Mortality Was Either the Primary or a Secondary Outcome. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 2 | 7 |
| 2024 October | 38 | 18 | 56 |
| 2024 September | 31 | 20 | 51 |
| 2024 August | 51 | 32 | 83 |
| 2024 July | 34 | 17 | 51 |
| 2024 June | 41 | 20 | 61 |
| 2024 May | 64 | 21 | 85 |
| 2024 April | 21 | 27 | 48 |
| 2024 March | 28 | 10 | 38 |
| 2024 February | 29 | 27 | 56 |
| 2024 January | 14 | 21 | 35 |
| 2023 December | 14 | 17 | 31 |
| 2023 November | 20 | 12 | 32 |
| 2023 October | 29 | 26 | 55 |
| 2023 September | 20 | 27 | 47 |
| 2023 August | 24 | 26 | 50 |
| 2023 July | 30 | 17 | 47 |
| 2023 June | 24 | 10 | 34 |
| 2023 May | 36 | 13 | 49 |
| 2023 April | 36 | 20 | 56 |
| 2023 March | 51 | 15 | 66 |
| 2023 February | 31 | 25 | 56 |
| 2023 January | 63 | 23 | 86 |
| 2022 December | 42 | 25 | 67 |
| 2022 November | 66 | 19 | 85 |
| 2022 October | 80 | 29 | 109 |
| 2022 September | 68 | 21 | 89 |
| 2022 August | 100 | 36 | 136 |
| 2022 July | 65 | 32 | 97 |
| 2022 June | 26 | 22 | 48 |
| 2022 May | 27 | 30 | 57 |
| 2022 April | 33 | 29 | 62 |
| 2022 March | 39 | 36 | 75 |
| 2022 February | 10 | 18 | 28 |
| 2021 October | 1 | 2 | 3 |
| 2021 March | 0 | 2 | 2 |
| 2021 January | 2 | 0 | 2 |
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