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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\u003EResults from the Aldosterone Receptor Blockade in Diastolic Heart Failure [Aldo-DHF; ISCRTN94726526] trial showed that spironolactone significantly improves diastolic function and blood pressure control, but not exercise capacity, in patients with diastolic heart failure.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EHeart Failure\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHypertensive Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EResults from the Aldosterone Receptor Blockade in Diastolic Heart Failure [Aldo-DHF; ISCRTN94726526] trial, presented by Burkert Mathias Pieske, MD, Medical University of Graz, Graz, Austria, showed that spironolactone significantly improves diastolic function and blood pressure (BP) control, but not exercise capacity, in patients with diastolic heart failure (DHF).\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EDHF accounts for more than 50% of all HF cases and clinical outcomes for these patients are poor. While no established therapy exists for DHF, there is strong evidence for a benefit from aldosterone antagonists in patients with reduced left ventricular ejection fraction (LVEF) [Chatterjee S et al. \u003Cem\u003EAm J Med\u003C\/em\u003E 2012], and aldosterone has been implicated in the pathogenesis of DHF via aldosterone receptor mediated myocardial fibrosis, hypertrophy, and vascular stiffening.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EAldo-DHF was a multicenter, randomized, placebo-controlled, double-blind, parallel-group study conducted to assess the safety and efficacy of the aldosterone receptor antagonist spironolactone on diastolic function and exercise capacity in patients with DHF after 1 year of therapy. Subjects were required to have documented stable chronic HF (NYHA II\/III), echocardiographic evidence of diastolic dysfunction \u2265Grade 1 or atrial fibrillation, EF \u226550%, and peak VO\u003Csub\u003E2\u003C\/sub\u003E \u0026lt;25 mL\/kg\/min. Co-primary endpoints were change in diastolic function (mitral inflow E velocity to tissue Doppler e\u2032 [E\/e\u2032 ratio]) and maximal exercise capacity (peak VO\u003Csub\u003E2\u003C\/sub\u003E on bicycle spiroergometry) at 12 months [Edelmann F et al. \u003Cem\u003EEur J Heart Fail\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003ESubjects (mean age 67 years, 52% women, \u226585% NYHA class II) were randomized to spironolactone (n=213) or placebo (n=209). Baseline E\/e\u2032 was 12.7\u00b13.6 and 12.8\u00b14.4 and peak VO\u003Csub\u003E2\u003C\/sub\u003E was 16.3\u00b13.6 and 16.4\u00b13.5 mL\/kg\/min in the spironolactone and placebo groups, respectively. Median NT-proBNP was 179 ng\/L in the spironolactone group (range, 81 to 276) and 148 ng\/L (range, 80 to 276) in the placebo group. Approximately 92% of patients had controlled hypertension at study entry. Mean estimated glomerular filtration rate was \u223c78 mL\/min\/1.73 m\u003Csup\u003E2\u003C\/sup\u003E.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ESpironolactone (25 mg QD) significantly improved diastolic function (p\u0026lt;0.001) but did not improve exercise capacity. Treatment effects were consistent across all subgroups analyzed. Spironolactone induced significant structural reverse remodeling (LV mass index p=0.009) and significant reductions in NT-proBNP plasma levels (p=0.03), but did not improve NYHA class, left atrial volume index, or quality of life.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003ESpironolactone was also associated with significant reductions in both systolic and diastolic BP beginning at 3 months, yet the effects of spironolactone on cardiac structure and function remained significant after adjusting for BP changes. Adverse events occurred significantly more often with spironolactone, including mild worsening of renal function (36% of spironolactone subjects vs 21% of placebo subjects; p\u0026lt;0.001); new or worsening anemia (16% vs 9%; p=0.03), gynecomastia (4% vs \u0026lt;1%; p=0.02), and nonsevere (\u0026lt;5.0 mmol\/L) increases in serum potassium levels (21% vs 11%; p=0.005). One patient in the spironolactone group died (vs none of the placebo subjects). There was no difference in the rate of hospitalization.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EAdditional data on the long-term efficacy and safety of spironolactone in patients with DHF will come from the Trial of Aldosterone Antagonist Therapy in Adults With Preserved Ejection Fraction Congestive Heart Failure [TOPCAT; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00094302\u0026amp;atom=%2Fspmdc%2F12%2F13%2F14.atom\u0022\u003ENCT00094302\u003C\/a\u003E] study, which is expected to report during 2013. TOPCAT is a multicenter, international, randomized, double-blind, placebo-controlled trial of spironolactone in 3515 adults with HF and LVEF \u226545%. The trial duration is \u223c6 years with an expected average subject follow-up of 3.45 years. The primary endpoint is a composite of cardiovascular mortality, aborted cardiac arrest, or hospitalization for the management of HF.\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\/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_openurl.js?nznb1f\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}