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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\u003EThis article discusses results of a pre-defined subgroup analysis from the bosentan for inoperable chronic thromboembolic pulmonary hypertension [BENEFiT] trial. The BENEFiT study is the first double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of bosentan for patients with inoperable chronic thromboembolic pulmonary hypertension, one of the leading causes of pulmonary arterial hypertension.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ehypertensive disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ethrombotic disorders clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EIrene Lang, MD, Medical University of Vienna, Austria, presented the results of a pre-defined subgroup analysis from the bosentan for inoperable chronic thromboembolic pulmonary hypertension (BENEFiT) trial. The BENEFiT study is the first double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of bosentan for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), one of the leading causes of pulmonary arterial hypertension (PAH).\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003ECTEPH is characterized by obstruction of pulmonary vessels with organized thromboemboli. The obstruction promotes increased pulmonary vascular resistance, progressive PAH, and, subsequently, right heart failure. The treatment of choice for CTEPH is the surgical removal of the thrombus in the major pulmonary vessels (pulmonary endarterectomy). However, as many as 50% of patients may not be candidates for this surgery [Nick H \u0026amp; Kim S. \u003Cem\u003EAmThorac Soc\u003C\/em\u003E 2006], and among patients who do undergo pulmonary endarterectomy, PAH persists or recurs in 10\u201320% [Dartevelle P et al. \u003Cem\u003EEur Respir J\u003C\/em\u003E 2004]. Thus, other treatment options are needed. Prof. Lang and her colleagues chose to evaluate the use of bosentan in this setting because of its vasodilatory effects, which would reduce pulmonary vascular resistance.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EThe BENEFIT trial involved 157 patients who were randomly assigned to receive bosentan (n=77) or placebo (n=80). The initial dose of bosentan was 62.5 mg BID for 4 week s, followed by 125 mg BID for 12 week s. The primary endpoints were pulmonary vascular resistance and 6-minute walk distance. Secondary endpoints included cardiac index, the level of N-terminal brain natriuretic propeptide (NT-pro-BNP), and the Borg dyspnea index (a measure of breathlessness). Subgroup analysis was performed to compare the treatment effects of bosentan (at 16 weeks) for the 113 patients who were not candidates for surgery (55 patients in the bosentan group; 58 in the placebo group) with the effects for the 44 patients who had persistent or recurrent PAH after pulmonary endarterectomy (22 patients in each group).\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EProf. Lang reported that treatment with bosentan produced clinically relevant improvement in cardiac hemodynamic characteristics. Bosentan significantly reduced the pulmonary vascular resistance in both groups (p\u0026lt;0.0001), with a 17.5% reduction for inoperable patients and a 32.5% reduction for patients with persistent or recurrent PAH after pulmonary endarterectomy (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Bosentan also significantly increased the cardiac index (mean 0.31 vs 0.25; p=0.0007) and significantly decreased the level of NT-pro-BNP (mean \u2212654 vs \u2212526; p\u0026lt;0.05) compared with placebo. Treatment with bosentan led to improvement in the Borg dyspnea index in patients with inoperable CTEPH but not in patients who underwent surgery (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E).\u003C\/p\u003E\n         \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\/7\/5\/14\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Bosentan Reduced PVR.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-889830574\u0022 data-figure-caption=\u0022Bosentan Reduced PVR.\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\/7\/5\/14\/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\/7\/5\/14\/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\/7\/5\/14\/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\/11196\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\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-6\u0022 class=\u0022first-child\u0022\u003EBosentan Reduced PVR.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cdiv id=\u0022F2\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\/7\/5\/14\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Borg Dyspnea Index Improved in Patients with Inoperable CTEPH.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-889830574\u0022 data-figure-caption=\u0022Borg Dyspnea Index Improved in Patients with Inoperable CTEPH.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/5\/14\/F2.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\/7\/5\/14\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\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\/7\/5\/14\/F2.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\/11199\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\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EBorg Dyspnea Index Improved in Patients with Inoperable CTEPH.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EBosentan did not improve the 6-minute walk distance, the other primary endpoint of the study, in either group (\u221211.5 meters in patients with persistent\/recurrent PAH and 8.8 meters in inoperable patients; p=0.5449). Prof. Lang suggested that this is most likely because the 16-week time point was not long enough for a difference in exercise capacity to occur. She added, \u201cThese are also older patients [mean age, 63 years] with many comorbidities, perhaps further diluting any change in the 6-minute walk test.\u201d The safety of bosentan was consistent with that found in other studies of the drug for PAH.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EIn concluding, Prof. Lang noted, \u201cPrognosis in CTEPH patients is highly related to hemodynamics and hemodynamics is a limitation to surgery. So, we may be benefiting patients long-term or, in some cases, actually getting inoperable patients improved hemodynamically to where they can undergo surgery.\u201d She added, \u201cThe results suggest we do have a medical option now for a no-option population.\u201d\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2007 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\/7\/5\/14.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?nzm8m1\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?nzm8m1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}