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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\u003ESpironolactone treatment of heart failure (HF) with preserved ejection fraction (HFpEF) did not significantly reduce cardiovascular death, hospitalization due to HF, or resuscitated cardiac arrest compared with placebo. This article presents updated data from the Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function trial [TOPCAT; Shah SJ et al. \u003Cem\u003ECirc Heart Fail\u003C\/em\u003E 2012].\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\u003ECardiology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EHeart Failure\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology \u0026amp; Cardiovascular Medicine\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ESpironolactone treatment of heart failure (HF) with preserved ejection fraction (HFpEF) did not significantly reduce cardiovascular death, hospitalization due to HF, or resuscitated cardiac arrest compared with placebo. Bertram Pitt, MD, University of Michigan School of Medicine, Ann Arbor, Michigan, USA, presented updated data from the Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function trial [TOPCAT; Shah SJ et al. \u003Cem\u003ECirc Heart Fail\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EPrevious trials have demonstrated that mineralocorticoid receptor antagonists improve survival in patients with mild to severe reduced ejection fraction and postmyocardial infarction left ventricular dysfunction compared with placebo [Zannad F et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011; Pitt B et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2003; Pitt B et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 1999]. The purpose of the TOPCAT trial was to evaluate the effect of spironolactone in patients with HFpEF.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn the multicenter TOPCAT trial, 3445 patients with HFpEF were randomly assigned to receive a target dose of 30 mg of spironolactone (n=1722) or placebo (n=1723) over a mean follow-up of 3.3 years [Desai AS et al. \u003Cem\u003EAm Heart J\u003C\/em\u003E 2011]. Randomly assigned patients had a mean age of 69 years and a New York Health Association class II or III HF, with a mean left ventricular ejection fraction of 56% [Shah SJ et al. \u003Cem\u003ECirc Heart Fail\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe primary outcome was a composite of cardiovascular death, hospitalization due to HF, or resuscitated cardiac arrest. In the spironolactone and placebo arms, 34.3% and 31.4% of patients prematurely discontinued the medication by the end of the study, respectively.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThere was no significant difference in the primary outcome with spironolactone (18.6%) compared to placebo (20.4%) at 72 months (HR, 0.89; 95% CI, 0.77 to 1.04; p=0.138) [Pitt B et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2014]. Although the primary end point was not significant, there were promising trends for the individual components, including a lower rate of HF hospitalization with spironolactone compared with placebo at 72 months (HR, 0.83; 95% CI, 0.69 to 0.99; p=0.042).\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EInterestingly, the rate of reaching the primary outcome varied by geographic region. Patients from the United States, Canada, Argentina, and Brazil had a rate of 12.6 per 100 patient-years, compared with 2.3 per 100 patient-years in patients from Russia and the Republic of Georgia. Similarly, the HR varied. In the United States, Canada, Argentina, and Brazil, the HR was 0.82 (95% CI, 0.69 to 0.98), compared with 1.10 (95% CI, 0.79 to 1.51) in Russia and the Republic of Georgia; however, these differences did not result in a statistically significant interaction (interaction p=0.122).\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EThere were no significant differences in the number of patients who experienced serious adverse events or total reports of adverse events. However, hyperkalemia occurred in 18.7% of patients who received spironolactone, compared with 9.1% who received placebo (p\u0026lt;0.001). In contrast, the placebo arm demonstrated greater rates of hypokalemia compared with the spironolactone arm (p\u0026lt;0.001). In addition, creatinine above the upper limit of reference occurred more frequently in the spironolactone arm compared with the placebo arm (HR, 1.49; 95% CI, 1.18 to 1.87; p\u0026lt;0.001).\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EDr. Pitt concluded by stating that the results of the TOPCAT trial do not show a benefit of spironolactone treatment in patients with HFpEF, although the observation of an associated decrease in hospitalization for HF as an individual component is promising and warrants further study. The geographic heterogeneity in patient risk complicates the conclusions of this study.\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\/12\/21.2.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?nzp5pe\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}