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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\u003EPatients with systemic sclerosis pulmonary arterial hypertension (SSc-PAH) have a worse prognosis than those with idiopathic PAH. Although the specific mechanisms are not known, it is thought to be related to persistent right ventricular dysfunction and pulmonary vascular remodeling despite guideline-directed management with a single agent for PAH. This article discusses a 36-week, open-label, multicenter observational study evaluating upfront therapy with 2 drugs, tadalafil and ambrisentan, that target distinct pathways in treatment-na\u00efve patients with SSc-PAH [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01178073\u0026amp;atom=%2Fspmdc%2F14%2F11%2F13.1.atom\u0022\u003ENCT01178073\u003C\/a\u003E; Gashouta MA et al. \u003Cem\u003EAm J Respir Crit Care Med\u003C\/em\u003E].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EPulmonary Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatological Autoimmune Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EThromboembolic Disease Hypertensive Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EPulmonary Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatological Autoimmune Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EThromboembolic Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPulmonary \u0026amp; Critical Care\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHypertensive Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EPatients with systemic sclerosis pulmonary arterial hypertension (SSc-PAH) have a worse prognosis than those with idiopathic PAH. Although the specific mechanisms are not known, it is thought to be related to persistent right ventricular (RV) dysfunction and pulmonary vascular remodeling despite guideline-directed management with a single agent for PAH. Dr. Mohamed A. Gashouta, MD, St. Luke\u0027s Hospital, Chesterfield, Missouri, USA, presented a 36-week, open-label, multicenter observational study evaluating upfront therapy with 2 drugs, tadalafil and ambrisentan, that target distinct pathways in treatment-na\u00efve patients with SSc-PAH [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01178073\u0026amp;atom=%2Fspmdc%2F14%2F11%2F13.1.atom\u0022\u003ENCT01178073\u003C\/a\u003E; Gashouta MA et al. \u003Cem\u003EAm J Respir Crit Care Med\u003C\/em\u003E].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe presenter reported findings for 17 of the 25 patients with SSc-PAH who had been treated with tadalafil 40 mg daily, a phosphodiesterase inhibitor, and ambrisentan 10 mg daily, an endothelin antagonist. The patients (mean age, 58.8 years) were predominantly female (88%), with limited (94%) as opposed to diffuse (6%) SSc-PAH disease. The mean baseline pulmonary arterial pressure (PAP) was 40 \u00b1 16 mm Hg and pulmonary capillary wedge pressure (PCWP) was 9 \u00b1 3.5 mm Hg.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe first primary end point, RV mass, as measured by computed magnetic resonance imaging, was significantly reduced over 36 weeks from 21.7 \u00b1 10.6 g\/m\u003Csup\u003E2\u003C\/sup\u003E to 18.0 \u00b1 6.7 g\/m\u003Csup\u003E2\u003C\/sup\u003E (p=0.04) with the combination therapy. The second primary end point, pulmonary vascular resistance (PVR), was also significantly reduced from baseline (8.1 \u00b1 58 woods units) to 36 weeks (3.9 \u00b1 3.5 woods units; p=0.0001).\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EPrevious work by this group showed that pulmonary compliance (Pca; stroke volume over pulmonary pulse pressure) was an indicator of poor prognosis and survival in SSc-PAH [Campo A et al. \u003Cem\u003EAm J Respir Crit Care Med\u003C\/em\u003E 2010]. The authors found that Pca, a secondary end point, was significantly improved from baseline (1.9 \u00b1 1.2) to 36 weeks (2.9 \u00b1 1.3; p=0.0007) with the combination therapy. There were also improvements in the secondary end points of ventricular mass index (VMI; 0.31 \u00b1 0.11 at baseline to 0.27 \u00b1 0.08 at 36 weeks; p=0.03) and 6-minute walking distance (6MWD; 361.3 \u00b1 122.3 minutes at baseline to 405.5 \u00b1 90 at 36 weeks; p=0.003). The combination treatment also significantly improved RV stroke volume (76.7 \u00b1 16.5 mL to 94.6 \u00b1 17.7 mL; p=0.007) and RV end systolic volume (RV ESV; 89.8 \u00b1 28.3 mL to 73.1 \u00b1 28.8 mL; p=0.02) over the 36 weeks.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThese results suggest that treatment with tadafil and ambrisentan in treatment-na\u00efve patients with SSc-PAH leads to improvement in a number of clinical (6MWD), functional (RV mass index, VMI, RV ESV), and hemodynamic (PVR, Pca, stroke volume) parameters. Additional larger, randomized studies are necessary to determine if combination therapy is superior to guideline-based therapy and whether it results in a survival benefit.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\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\/14\/11\/13.1.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_openurl.js?nzp1rp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}