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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\u003EIn about half of all patients with heart failure (HF), the ejection fraction (EF) is normal or nearly normal, despite high morbidity and mortality in these patients. Now, the findings of a Phase 2 trial suggest that a first-in-class angiotensin receptor neprilysin inhibitor, LCZ696, may be beneficial for patients who have HF with preserved EF. This article discusses the Prospective Comparison of ARNI with ARB (angiotensin receptor blocker) on Management of Heart Failure with Preserved Ejection Fraction [PARAMOUNT; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00887588\u0026amp;atom=%2Fspmdc%2F12%2F13%2F11.atom\u0022\u003ENCT00887588\u003C\/a\u003E] trial.\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\u003EIn about half of all patients with heart failure (HF), the ejection fraction (EF) is normal or nearly normal, despite high morbidity and mortality in these patients. Now, the findings of a Phase 2 trial suggest that a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), LCZ696, may be beneficial for patients who have HF with preserved EF.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ELCZ696 is the first agent to be associated with 2 powerful predictors of outcome in HF: reduction in the concentration of N-terminal prohormone brain natriuretic peptide (NT-proBNP) and decrease in the size of the left atrium, said Scott D. Solomon, MD, Brigham and Women\u0027s Hospital, Boston, Massachusetts, USA, who reported the findings. The study was published to coincide with its presentation at the ESC 2012 Congress [Solomon SD et al. \u003Cem\u003ELancet\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EDr. Solomon explained that LCZ696 simultaneously blocks the renin angiotensin system while augmenting the body\u0027s intrinsic natriuretic peptide system through neprilysin inhibition. These dual effects may be important in the treatment of HF with preserved EF.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe Prospective Comparison of ARNI with ARB (angiotensin receptor blocker) on Management of Heart Failure with Preserved Ejection Fraction [PARAMOUNT; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00887588\u0026amp;atom=%2Fspmdc%2F12%2F13%2F11.atom\u0022\u003ENCT00887588\u003C\/a\u003E] trial enrolled 308 patients who were randomly assigned to LCZ696 (200 mg BID after 1 week each of 50 and 100 mg BID) or the ARB valsartan (160 mg BID after 1 week each of 40 and 80 mg BID). The primary endpoint, NT-proBNP, was evaluated as the ratio of the concentration at 12 weeks to that at baseline. Secondary objectives included echocardiographic measures of left atrial size, left ventricular size and function, and diastolic function, and safety and tolerability.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EOver 12 weeks, both LCZ696 and valsartan led to a decrease in the NT-proBNP concentration, with a greater reduction in the LCZ696 group (from 783 to 605 pg\/mL) than in the valsartan group (from 862 to 835 pg\/mL; HR, 0.77; 95% CI, 0.64 to 0.92; p=0.005). The decrease was evident at 4 weeks and was sustained over the 12-week period (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). The NT-proBNP concentration continued to decrease in both groups over 36 weeks; the difference no longer significant at that time (p=0.20).\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\/12\/13\/11\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Comparison of the Primary Endpoint\u0026#x2014;Concentration of NT-proBNP at 12 Weeks.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1858149780\u0022 data-figure-caption=\u0022Comparison of the Primary Endpoint\u0026#x2014;Concentration of NT-proBNP at 12 Weeks.\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\/12\/13\/11\/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\/12\/13\/11\/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\/12\/13\/11\/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\/14182\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\u003EComparison of the Primary Endpoint\u2014Concentration of NT-proBNP at 12 Weeks.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from The \u003Cem\u003ELancet\u003C\/em\u003E; The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: A phase 2 double-blind randomised controlled trial. Solomon SD et al. 2012;doi:10.1016\/S0140\u20136736(12)61227\u20136.\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\u003EA similar treatment effect was found in all predefined subgroups, including those defined by age (\u226565 vs \u0026lt;65 years), gender, systolic blood pressure (\u0026gt;140 vs \u2264140 mm Hg), presence or absence of diabetes, EF (\u226550% vs \u0026lt;50%), presence or absence of atrial fibrillation, previous hospitalization for HF, NYHA class (III vs II), and median NT-proBNP concentration (\u0026gt;median vs \u2264median).\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003ELCZ696 was also associated with a significant decrease in the volume of the left atrium at 36 weeks (p=0.003), and the left atrial dimension (p=0.034). In addition, the NYHA class improved in more patients in the LCZ696 group than in the valsartan group at both 12 and 36 weeks; the difference was significant at the latter time period (p=0.05). The frequency of serious adverse events was similar between therapies: 15% with LCZ696 and 20% with valsartan. The number of patients with hypotension, renal dysfunction, or hyperkalemia did not differ between groups.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EProspective studies are needed to determine whether the effects found in PARAMOUNT translate into improved clinical outcomes.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 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\/12\/13\/11.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?nznay2\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?nznay2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}