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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThe Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure [ASCEND-HF; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00475852\u0026amp;atom=%2Fspmdc%2F10%2F10%2F20.atom\u0022\u003ENCT00475852\u003C\/a\u003E] was designed as the result of an independent safety and efficacy review of nesiritide data in an attempt to assess the concerns that were raised by the 2005 reports more fully.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHeart Failure\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EResults from a large, prospective clinical trial that was designed to assess the safety and efficacy of nesiritide that was added to standard care in patients with acute decompensated heart failure (ADHF) showed that nesiritide is safe but offers no significant benefit in terms of mortality or HF rehospitalization rates. There was a modest improvement in dyspnea. Renal function was not compromised.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ENesiritide is a recombinant intravenous (IV) formulation of human B-type natriuretic peptide that is known to reduce dyspnea and intracardiac filling pressures within 3 hours of administration in patients with ADHF. It was approved in 2001 to reduce pulmonary capillary wedge pressure and improve dyspnea and was widely used until 2005, when the results of two meta-analyses questioned its safety, noting a higher mortality rate [Sackner-Bernstein JD et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2005] and increased risk of kidney injury [Sackner-Bernstein JD et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2005]. The Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00475852\u0026amp;atom=%2Fspmdc%2F10%2F10%2F20.atom\u0022\u003ENCT00475852\u003C\/a\u003E) was designed as the result of an independent safety and efficacy review of nesiritide data in an attempt to assess the concerns that were raised by the 2005 reports more fully.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EASCEND-HF was a prospective, double-blind, randomized trial in 7141 patients (median age 67 years; \u223c34% women) with ADHF, dyspnea at rest or with minimal activity, and one clinical sign and one objective measure of HF. Within 24 hours of hospitalization, subjects were randomly assigned to receive either IV nesiritide (n=3496; initial IV bolus of 2 \u03bcg\/kg at the discretion of the investigator, followed by continuous IV infusion of 0.01 \u03bcg\/kg) or matching placebo (n=3511) for up to 7 days, along with usual care. The duration of treatment was based on the investigator\u0027s assessment of clinical improvement.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe two coprimary endpoints were rehospitalization for HF\/all-cause mortality within 30 days and dyspnea at 6 or 24 hours (p-value for significance prespecified at \u22640.005 for both assessments or \u22640.0025 for either assessment). Improvement in dyspnea was self-reported using a 7-point Likert scale: markedly worse, moderately worse, minimally worse, no change, minimally better, moderately better, and markedly better. Safety endpoints included impact on renal function (25% decrease in eGFR through Day 30) and hypotension.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThere was no difference in either of the coprimary endpoints between treatment groups. The rate of HF rehospitalization or 30-day all-cause mortality was 9.4% for subjects who were treated with nesiritide versus 10.1% for placebo-treated patients (HR, 0.93; 95% CI, 0.81 to 1.08; p=0.31). The observed reduction in overall dyspnea was modest and did not meet the preestablished criteria for significance. At 6 hours, 44.5% of nesiritide subjects reported markedly or moderately better dyspnea versus 42.1% of subjects who received placebo (p=0.030). At 24 hours, the rates were 68.2% for nesiritide patients versus 66.1% for placebo patients (p=0.007; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Marked improvement in dyspnea was less frequent with nesiritide at 6 hours (15.0% vs 13.4%; p=0.03) and 24 hours (30.4% vs 27.5%; p=0.007). Neither finding was statistically significant, based on the predefined significant p-value of \u22640.005.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/10\/20\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Coprimary Endpoint: 6- and 24-Hour Dyspnea.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-797409548\u0022 data-figure-caption=\u0022Coprimary Endpoint: 6- and 24-Hour Dyspnea.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/10\/20\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/10\/20\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/10\/10\/20\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11380\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003ECoprimary Endpoint: 6- and 24-Hour Dyspnea.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from A. Hernandez, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EThere was no difference in renal function between treatment groups (p=0.11). Subjects who received nesiritide experienced significantly (p\u0026lt;0.001) more hypotension compared with those who received placebo through Day 10 or discharge (HR, 11.3; 95% CI, 9.4 to 13.1).\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2010 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/10\/10\/20.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzmn71\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmn71\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}