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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.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 atrial fibrillation and moderate renal dysfunction have a higher risk of stroke and bleeding than patients with normal renal function, but respond favorably to reduced-dose rivaroxaban compared with warfarin, according to new findings from the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00403767\u0026amp;atom=%2Fspmdc%2F11%2F10%2F25.atom\u0022\u003ENCT00403767\u003C\/a\u003E].\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\u003ERenal Insufficiency\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EArrhythmias\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECerebrovascular Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERenal Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EPatients with atrial fibrillation (AF) and moderate renal dysfunction have a higher risk of stroke and bleeding than patients with normal renal function, but respond favorably to reduced-dose rivaroxaban compared with warfarin, according to new findings from the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00403767\u0026amp;atom=%2Fspmdc%2F11%2F10%2F25.atom\u0022\u003ENCT00403767\u003C\/a\u003E].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EKeith A. A. Fox, MD, University of Edinburgh, Edinburgh, United Kingdom, presented results from the ROCKET-AF prespecified renal impairment substudy.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe ROCKET-AF trial compared the safety and efficacy of rivaroxaban 20 mg daily (15 mg for patients with a calculated creatinine clearance [CrCl] 30 to 49 ml\/min) to standard dose-adjusted warfarin in 14,264 patients with AF and additional risk factors for stroke. In the primary study analysis in the \u201cper protocol\u201d cohort, rivaroxaban was non-inferior to warfarin in reducing the risk of stroke or systemic embolism ([SSE]; 1.71% vs 2.16% per year; HR, 0.79; 95% CI, 0.66 to 0.96; p\u0026lt;0.001 for noninferiority) [Patel M et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011]. Of note, there was no statistically significant difference between the treatment groups when all events between randomization and the end of the study were analyzed in an intention-to-treat analysis (2.1% vs 2.4%; p=0.12 for superiority).\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003ERivaroxaban is predominantly metabolized by the liver, although one-third of the drug is cleared by the kidneys and excreted unchanged in the urine. The current substudy evaluated the 2950 patients in the \u201cper protocol\u201d cohort with a baseline CrCl of 30 to 49 ml\/min who received a reduced-dose of rivaroxaban (15 mg\/day) compared to those treated with dose-adjusted warfarin with a target INR of 2.0 to 3.0.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ECompared with patients with normal renal function, patients in the renal dysfunction substudy were older, had a higher CHADS\u003Csub\u003E2\u003C\/sub\u003E risk score, and were more likely to have a history of SSE. Patients with renal impairment had higher rates of stroke and bleeding than patients with preserved renal function, regardless of study treatment.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThere was no evidence of a statistical interaction between renal function and the effect of rivaroxaban on the primary efficacy (interaction p=0.45) or safety endpoint (interaction p=0.76; \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). Among patients with moderate renal dysfunction, patients randomized to rivaroxaban, compared with those randomized to warfarin, had annualized rates of SSE 2.32% and 2.77% respectively (HR, 0.84; 95% CI, 0.57 to 1.23). For the primary safety endpoint of major plus nonmajor clinically relevant bleeding, the corresponding rates were 17.8% and 18.3% (HR, 0.98; 0.84 to 1.14).\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\/12448\/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\/12448\/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\/12448\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 \n            \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EPrimary Endpoints and Bleeding Rates.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-10\u0022\u003EFatal bleeding was reduced with rivaroxaban compared to warfarin among both patients with moderate renal dysfunction (0.28% vs 0.74%; HR, 0.39; 0.15 to 0.99) and in those with mild\/normal renal function (0.23% vs 0.43%; HR, 0.55; 0.32 to 0.93), with no evidence of statistical heterogeneity (interaction p=0.53). The rates of intracranial hemorrhage in the rivaroxaban versus warfarin groups for patients with renal impairment were 0.71% versus 0.88% (HR, 0.81; 0.41 to 1.60) and among those with normal renal function 0.44% versus 0.71% (HR, 0.62; 0.42 to 0.92). Despite the numeric difference in the hazard ratios, the statistical test for interaction was not significant (p=0.51), in part related to the small absolute number of events in the former group. Gastrointestinal bleeding was more common with rivaroxaban than warfarin, both for patients with renal impairment (2.88% vs 1.77%; p=0.02) and normal renal function (1.79% vs 1.12%; p=0.0002).\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EFindings from this ROCKET-AF substudy were consistent with those from the overall trial. In patients with moderate renal impairment, reduced-dose rivaroxaban preserved the benefit of warfarin in preventing SSE, and in the \u201cper protocol analysis\u201d yielded lower rates than warfarin. The rates of bleeding and adverse events with reduced dose rivaroxaban compared with warfarin were similar, with fewer fatal bleeds.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section ref-list\u0022 id=\u0022ref-list-1\u0022\u003E\u003Ch2 class=\u0022\u0022\u003EAdditional Reading\u003C\/h2\u003E\u003Col class=\u0022cit-list ref-use-labels\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022ref-label ref-label-empty\u0022\u003E\u003C\/span\u003E\n            \u003Cdiv class=\u0022cit ref-cit ref-journal no-rev-xref\u0022 id=\u0022cit-11.10.25.1\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Col class=\u0022cit-auth-list\u0022\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-auth\u0022\u003E\u003Cspan class=\u0022cit-name-surname\u0022\u003EFox\u003C\/span\u003E  \u003Cspan class=\u0022cit-name-given-names\u0022\u003EKAA\u003C\/span\u003E\u003C\/span\u003E, \u003C\/li\u003E\u003Cli\u003E\u003Cspan class=\u0022cit-etal\u0022\u003Eet al\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Ccite\u003E. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EEur Heart J\u003C\/abbr\u003E \n               \u003Cspan class=\u0022cit-pub-date\u0022\u003E2011\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003C\/li\u003E\u003C\/ol\u003E\u003C\/div\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\/11\/10\/25.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?nzmz01\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?nzmz01\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}