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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\u003EThis article presents results of the Ranolazine in Atrial Fibrillation Following an Electrical Cardioversion randomized trial [RAFFAELLO; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01534962\u0026amp;atom=%2Fspmdc%2F14%2F9%2F24.atom\u0022\u003ENCT01534962\u003C\/a\u003E], an international, double-blind, parallel, Phase 2, dose-ranging study testing three oral ranolazine doses. The results demonstrated safety and provided favorable findings with regard to efficacy for patients with atrial fibrillation.\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\u003EArrhythmias\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EArrhythmias\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EGaetano De Ferrari, MD, Policlinico S Matteo and University of Pavia, Pavia, Italy, presented results of the Ranolazine in Atrial Fibrillation Following an Electrical Cardioversion randomized trial [RAFFAELLO; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01534962\u0026amp;atom=%2Fspmdc%2F14%2F9%2F24.atom\u0022\u003ENCT01534962\u003C\/a\u003E], an international, double-blind, parallel, Phase 2, dose-ranging study testing three oral ranolazine doses. The results demonstrated safety and provided favorable findings with regard to efficacy for patients with atrial fibrillation (AF).\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAlthough antiarrhythmic medications are widely used in managing patients with AF, with the aim of reducing mortality and hospitalizations, their use has been limited by a combination of toxicity and only modest efficacy. Ranolazine is a relatively new drug approved for the management of chronic angina that blocks late sodium currents, and although it also reduces supraventricular arrhythmias, its use by patients with AF is poorly documented [Zimetbaum P. \u003Cem\u003ECirculation\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe RAFFAELLO trial conducted by Prof. De Ferrari and colleagues was the first study to prospectively examine the efficacy and safety of ranolazine in patients with persistent AF. To be included in the study, patients were required to be aged \u226518 years, have persistent AF of 7 days to 6 months in duration, and be suitable for direct-current cardioversion (DCC). Exclusion criteria included congestive heart failure (NYHA Class 3 or 4) and the use of Class 1 or 3 antiarrhythmic agents in the previous 3 days (or 2 weeks and 3 months in the cases of dronedarone and oral amiodarone, respectively).\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe primary end point was median time from randomization to first documented AF recurrence. Secondary end points included time to first documented and confirmed AF recurrence and time to first documented AF recurrence in patients who remained in sinus rhythm 2 days after DCC.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EDuring the 16-week study, electrocardiograms (ECGs) were performed daily and in the case of symptoms, using transtelephonic ECG (TT-ECG) devices. ECGs were then transmitted to a central core ECG laboratory for interpretation.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EIntention-to-treat (ITT) analysis was performed on 238 study participants, who were randomly assigned 1:1:1:1 to ranolazine (RAN) 375 mg twice daily (BID) (n=65), 500 mg BID (n=60), or 750 mg BID (n=58), or placebo (n=55). The most common ECG interpretation was stable sinus rhythm (79.1%), followed by AF (11.5%), and the remaining 9.3% comprised poor-quality recordings that were unable to be assessed.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EOverall safety was favorable, with a similar incidence of all treatment-emergent side effects in the RAN 375 (78.5%), RAN 500 (76.7%), RAN 750 (72.4%), and placebo (74.5%) groups. The incidence of drug-related side effects appeared to be dose dependent (10.8% vs 15.0% vs 22.4% vs 3.6%), was mostly mild, and involved dizziness, fatigue, constipation, and nausea. Severe side effects were rare, comprising pancreatitis (RAN 375; n=1), orthostatic hypotension (RAN 750; n=1), atrial flutter (RAN 750; n=1), and sudden cardiac death (placebo; n=1).\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EThe primary efficacy endpoint of this study was not met, because no single dose of ranolazine significantly prolonged time to first AF recurrence. In a prespecified analysis of time to first AF recurrence, however, excluding patients who relapsed within the first 48 hours, there was a trend toward significance for the two higher doses of ranolazine (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E).\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\/14\/9\/24\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Prespecified Analysis of Time to First Atrial Fibrillation Recurrence\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-739584668\u0022 data-figure-caption=\u0022Prespecified Analysis of Time to First Atrial Fibrillation Recurrence\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\/14\/9\/24\/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\/14\/9\/24\/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\/14\/9\/24\/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\/15904\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-10\u0022 class=\u0022first-child\u0022\u003EPrespecified Analysis of Time to First Atrial Fibrillation Recurrence\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from GF De Ferrari, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-11\u0022\u003EAn exploratory analysis of the different dose groups also showed that, whereas the 375-mg dose was ineffective, the two higher doses showed promising trends toward efficacy in freedom from AF (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F2\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\/14\/9\/24\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Freedom From Atrial Fibrillation\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-739584668\u0022 data-figure-caption=\u0022Freedom From Atrial Fibrillation\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/9\/24\/F2.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\/14\/9\/24\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\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\/14\/9\/24\/F2.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\/15906\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 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-12\u0022 class=\u0022first-child\u0022\u003EFreedom From Atrial Fibrillation\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from GF De Ferrari, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-13\u0022\u003EThe study did suggest very good safety and tolerability of ranolazine. In addition, combining data from the 500- and 750-mg-dose groups and comparing them with either placebo or the ineffective 375-mg-dose group suggested a 25% to 30% reduction in overall recurrence of AF, concluded Prof. De Ferrari.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EThese data show favorable findings that support further investigation in the use of ranolazine after cardioversion by patients with atrial fibrillation.\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\/9\/24.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?nzp6v1\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?nzp6v1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}