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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 reviews tools for risk stratification for stroke and bleeding among patients with atrial fibrillation (AF). The CHADS2 score is frequently used to estimate the risk of stroke in AF patients and to help determine the appropriateness of anticoagulant therapy. Also discussed are the benefit-risk of warfarin and the new oral anticoagulants (OACs), multiple clinical trials, as well as the measurement and monitoring of the anticoagulant effects of new OACs.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EArrhythmias\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECerebrovascular Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology \u0026amp; Cardiovascular Medicine\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ETools for risk stratification for stroke and bleeding among patients with atrial fibrillation (AF) were reviewed by Gregory Lip, MD, Centre for Cardiovascular Sciences at City Hospital, Birmingham, United Kingdom. The CHADS\u003Csub\u003E2\u003C\/sub\u003E score is frequently used to estimate the risk of stroke in AF patients and to help determine t happropriateness of anticoagulant therapy. However, Prof. Lip noted that one of the limitations of this tool is that in patients with a CHADS\u003Csub\u003E2\u003C\/sub\u003E score of 0, the stroke rate ranges from 0.8% to 3.2% per year [Olesen JB et al. \u003Cem\u003EThromb Haemost\u003C\/em\u003E 2012], and there was significant undertreatment of high-risk patients.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EIn this regard, the CHA\u003Csub\u003E2\u003C\/sub\u003EDS\u003Csub\u003E2\u003C\/sub\u003E-VASc score is superior to CHADS\u003Csub\u003E2\u003C\/sub\u003E. As opposed to CHADS\u003Csub\u003E2\u003C\/sub\u003E, which defines age \u226575 years as a major stroke risk factor, the CHA\u003Csub\u003E2\u003C\/sub\u003EDS\u003Csub\u003E2\u003C\/sub\u003E-VASc score assigns 1 point for age 65 to 74 years and assigns extra weight (2 points) for age \u0026gt;75 years [Lip GYH et al. \u003Cem\u003EChest\u003C\/em\u003E 2010]. In addition, the CHA\u003Csub\u003E2\u003C\/sub\u003EDS\u003Csub\u003E2\u003C\/sub\u003E-VASc score adds vascular disease and female sex (if over age 65) as additional risk factors.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003ELow-risk patients by CHA\u003Csub\u003E2\u003C\/sub\u003EDS\u003Csub\u003E2\u003C\/sub\u003E-VASc are defined by a score of 0 (men) or 1 (women); these patients are uncommon and do not require antithrombotic therapy [Olesen JB et al. \u003Cem\u003EThromb Haemost\u003C\/em\u003E 2012]. All other AF patients with at least one stroke risk factor should be offered oral anticoagulant therapy.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe 2012 European Society of Cardiology guidance also recommends a bleeding risk scoring system, the HAS-BLED score [Camm AJ et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2012] which is easy to use and superior to other bleeding risk scores in predicting bleeding events [Lip GYH et al. \u003Cem\u003EClin Arrhythm Electrophysiol\u003C\/em\u003E 2012]. It allows for an informed assessment of bleeding risk and identification of potentially correctable risk factors for bleeding and Prof. Lip emphasized that it should not be used to exclude patients from oral anticoagulant therapy.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe benefit-risk of warfarin and the new oral anticoagulants (OACs) was examined by Elaine M. Hylek, MD, MPH, Boston University Medical Center, Boston, Massachusetts, USA. Warfarin is the most common medication implicated in emergency hospitalizations for adverse drug events in older adults in the United States [Budnitz DS et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011], being responsible for high rates of intracranial hemorrhage (ICH), gastrointestinal hemorrhage, and elevations in the International Normalized Ratio (INR) that require emergency hospitalization. Time spent in the therapeutic range is only 55% in warfarin recipients [Baker WL et al. \u003Cem\u003EJ Manag Care Pharm\u003C\/em\u003E 2009], confirming the difficulty in dosing and monitoring warfarin.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EAlternatives to warfarin are the direct thrombin inhibitors and factor Xa inhibitors. In the RE-LY trial, the oral direct thrombin inhibitor, dabigatran 150 mg BID, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage compared with warfarin [Connolly SJ et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009]. In patients aged \u226575 years, there was a trend toward a higher incidence of major bleeding with dabigatran than with warfarin.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EPatients with low INR variability and adequate time in the therapeutic range on warfarin have less to gain from a switch to twice daily dabigatran than patients with high INR variability. In patients with stable INR while on warfarin, the death rate and anticoagulant-related bleeding were significantly lower than in a comparator group (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E) [Witt DM et al. \u003Cem\u003EBlood\u003C\/em\u003E 2009]. Recent evidence from RE-LY indicates that a polymorphism in the rs2244613 gene, present in about one third of patients, predicts a lower risk of bleeding with dabigatran [Par\u00e9 G et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2013].\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\/13361\/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\/13361\/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\/13361\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-9\u0022 class=\u0022first-child\u0022\u003ESix-Month Event Rates in Warfarin-Treated Patients With Stable INR\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-13\u0022\u003EIn the ROCKET-AF trial there was no difference in the rate of major bleeding with rivaroxaban compared with warfarin though the former was associated with significantly lower rates of critical organ bleeding, death from bleeding, and ICH but comparatively higher rates of transfusion and a decrease in hemoglobin \u22652 g\/dL (\u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E) [Patel MR et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011]. In the ARISTOTLE trial, the rates of International Society on Thrombosis and Haemostasis major bleeding and ICH were significantly lower with apixaban compared with warfarin [Granger CB et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cdiv id=\u0022T2\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\/13363\/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\/13363\/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\/13363\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 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-14\u0022 class=\u0022first-child\u0022\u003ESafety Outcomes With Rivaroxaban\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-16\u0022\u003ELeft atrial appendage (LAA) closure is an option to prevent stroke in patients at high risk of stroke in whom long-term anticoagulation is contraindicated or in whom INR control cannot be achieved, said Amin Al-Ahmad, MD, Texas Cardiac Arrhythmia Institute, Austin, Texas, USA.\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003EEndocardial approaches to close the LAA are the Watchman LAA System and Coherex Medical. The Watchman, not currently approved in the United States, is a self-expanding nitrol frame structure with fixation barbs that engage the LAA wall when the delivery catheter is employed. In a randomized clinical trial of 707 AF patients [Holmes DR. \u003Cem\u003ELancet\u003C\/em\u003E 2009], the Watchman was found to be noninferior to warfarin on the primary efficacy endpoint (a composite of stroke, cardiovascular death, or systemic embolism). Periprocedural complications including cardiac perforation, pericardial effusion with tamponade, and device embolization occurred in 6% to 8% of patients. The Coherex WaveCrest System, also not currently approved in the United States, comes in three sizes to accommodate different ostial diameters, and can be used in a wide variety of LAA anatomies.\u003C\/p\u003E\u003Cp id=\u0022p-18\u0022\u003EPotential issues with endocardial approaches are incomplete closure, thrombus formation at follow-up, and an inability to retrieve the device if deployment is suboptimal.\u003C\/p\u003E\u003Cp id=\u0022p-19\u0022\u003EMeasurement and monitoring of the anticoagulant effects of new OACs, although not required routinely because of their predictable pharmacokinetics and a wide therapeutic window, may be useful in some situations, such as in patients with bleeding or at risk of bleeding or thromboembolism, said Graeme J. Hankey, MD, University of Western Australia, Perth, Australia.\u003C\/p\u003E\u003Cp id=\u0022p-20\u0022\u003EAntifactor Xa assays accurately measure the effects of the oral factor Xa inhibitors apixaban and rivaroxaban, depending on the calibrator [Doufils J et al. \u003Cem\u003EThromb Haemost\u003C\/em\u003E 2013; \u003Cem\u003EThromb Res\u003C\/em\u003E 2012]. When interpreting the Hemoclot assay for dabigatran, or the antifactor Xa assay for Xa inhibitors, the timing of the last tablet and the timing of the blood test must be known in order to get an idea of whether the blood concentration should be rising, plateauing, or falling [Mani H et al. \u003Cem\u003EJ Thromb Thrombolysis\u003C\/em\u003E 2013], said Prof. Hankey.\u003C\/p\u003E\u003Cp id=\u0022p-21\u0022\u003EThe other important laboratory test is creatinine clearance. A residual anticoagulant effect is unlikely if renal function is normal and it has been \u226524 hours since the last dose of OAC. A widely and rapidly available assay that correlates with a validated therapeutic window is awaited.\u003C\/p\u003E\u003Cp id=\u0022p-22\u0022\u003ESpecific antidotes to the new OACs are still under development. A monoclonal antibody against dabigatran (aDabi-Fab) has shown rapid reversal of the anticoagulant effect in \u003Cem\u003Eex vivo\u003C\/em\u003E clotting assays in a rat model [Schiele F et al. \u003Cem\u003EBlood\u003C\/em\u003E 2013]. A recombinant protein, r-antidote (PRT064445), to Xa inhibitors reversed the anticoagulant effects of these agents in a rat model [Lu G et al. \u003Cem\u003ENat Med\u003C\/em\u003E 2013]. Another potential antidote to Xa inhibitors is andexanet alfa, which has shown rapid and near complete reversal of apixaban\u0027s anticoagulant effect [\u003Ca href=\u0022http:\/\/investors.portola.com\/phoenix.zhtml?c=198136\u0026amp;p=irol-newsArticle\u0026amp;ID=1883157\u0026amp;highlight=\u0022\u003Ehttp:\/\/investors.portola.com\/phoenix.zhtml?c=198136\u0026amp;p=irol-newsArticle\u0026amp;ID=1883157\u0026amp;highlight=\u003C\/a\u003E]. PER 977 is a synthetic small molecule that acts as a universal reversal agent [Laulicht B et al. \u003Cem\u003ECirculation\u003C\/em\u003E (abstr 11395)].\u003C\/p\u003E\u003Cp id=\u0022p-23\u0022\u003EIn the past 5 years there have been many new developments in the management of AF. Additional information from studies of novel therapeutics will continue to help optimize therapy and reduce the risk of stroke or systemic embolization while minimizing bleeding for patients with AF.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 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\/13\/20\/33.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?nznju2\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?nznju2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}