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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\u003Cp id=\u0022p-1\u0022\u003ELCZ696 significantly reduced the composite primary outcome of cardiovascular death or heart failure (HF) hospitalization in patients with HF and reduced ejection fraction in the prospective trial Efficacy and Safety of LCZ696 Compared With Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure [PARADIGM-HF. New results from analyses of prespecified outcomes showed that HF progression is attenuated and fatal and that nonfatal worsening HF is delayed or prevented with LCZ696 when compared with enalapril, as discussed in this article.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EPARADIGM-HF\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eheart failure\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecardiology clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EThe first-in-class angiotensin receptor neprilysin inhibitor LCZ696\u2014compared with the gold standard treatment of enalapril\u2014significantly reduced the composite primary outcome of cardiovascular (CV) death or heart failure (HF) hospitalization in patients with HF and reduced ejection fraction in the prospective trial Efficacy and Safety of LCZ696 Compared With Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure [PARADIGM-HF; McMurray JJ et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2014]. The components of the primary outcome, as well as the secondary outcome of all-cause mortality, were also significantly reduced.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ENew results from analyses of prespecified outcomes showed that HF progression is attenuated and fatal and that nonfatal worsening heart failure (WHF) is delayed or prevented with LCZ696 when compared with enalapril, according to John J. V. McMurray, MD, University of Glasgow, Glasgow, Scotland, UK. LCZ696 combines a neprilysin inhibitor prodrug (sacubitril) and the angiotensin receptor blocker valsartan, thereby blocking both the AT\u003Csub\u003E1\u003C\/sub\u003E receptor and inhibiting the enzyme neprilysin, which breaks down natriuretic peptides and other vasoactive substances with beneficial effects in HF, to obtain incremental benefits beyond blockade of the renin angiotensin system alone.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn the original study, the median follow-up was 27 months, and the average daily dose at the last visit was LCZ696, 375 mg, and enalapril, 18.9 mg. The patients were aged 63.8 years; 22% were women; 60% had ischemic cardiomyopathy; and the mean left ventricular ejection fraction was about 29%.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EBased on patient and physician assessments, the proportion of patients with WHF at month 8 was lower with LCZ696 vs enalapril [Packer M et al. \u003Cem\u003ECirculation.\u003C\/em\u003E 2014]. For each domain measured by the Kansas City Cardiomyopathy Questionnaire, fewer patients in the LCZ696 group reported \u2265 5 points in deterioration (level considered to be clinically meaningful). Regarding change in NYHA class from baseline, more patients in the LCZ696 group improved (16.7% vs 14.9% with enalapril; \u003Cem\u003EP\u003C\/em\u003E = .0015), and fewer patients progressed to a higher NYHA class (5.4% vs 7.0%, respectively), while 78% of each group had no change.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ELCZ696 had a favorable influence on a number of parameters that are a measure of WHF\u2014including reductions in treatment failure (as measured by the need for treatment intensification), emergency department visits for HF, hospitalization for HF, intensive care unit admission, and use of inotropic drugs (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/15207\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/15207\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15207\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\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EEffect of Enalapril and LCZ696 on Outcomes Associated With Heart Failure Progression\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-11\u0022\u003EThe need for devices, ventricular assist devices, or heart transplant for WHF was numerically lower with LCZ696 vs enalapril (\u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/15164\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/15164\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15164\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\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \u003Cp id=\u0022p-12\u0022 class=\u0022first-child\u0022\u003ERate of Device Implantation, Ventricular Assist Device Insertion, and Transplant for Worsening Heart Failure\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-16\u0022\u003ENotably, all-cause hospitalization was reduced with LCZ696 as compared with enalapril, at about 110 fewer hospitalizations per 1000 patients, stated Prof McMurray. The number of admissions for any cause, including repeat episodes, was reduced (RR, 0.84; 95% CI, 0.78 to 0.91; \u003Cem\u003EP\u003C\/em\u003E \u0026lt; .001), as was the proportion of patients hospitalized (HR, 0.88; 95% CI, 0.82 to 0.94; \u003Cem\u003EP\u003C\/em\u003E \u0026lt; .001).\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003EThe rate of death for WHF was lower with LCZ696 vs enalapril (HR, 0.79; \u003Cem\u003EP\u003C\/em\u003E = .34) and was significant for all-cause death (HR, 0.84; \u003Cem\u003EP\u003C\/em\u003E \u0026lt; .001), CV death (HR, 0.80; \u003Cem\u003EP\u003C\/em\u003E = .00008), and sudden death (HR, 0.80; \u003Cem\u003EP\u003C\/em\u003E =.008).\u003C\/p\u003E\u003C\/div\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\/52\/23.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?nzod8d\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_tables.js?nzod8d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}