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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\u003EApixaban is an oral factor Xa inhibitor with prompt onset and offset of anticoagulation, twice-a-day dosing, and no need for coagulation monitoring. This article discusses the efficacy and safety of apixaban compared with warfarin in ARISTOTLE trial, and with aspirin in AVERROES Trial. This article also discusses the challenge of choosing anticoagulation therapy for patients with AF using the RE-LY, ROCKET, ARISTOTLE, and ENGAGE AF-TIMI 48 as examples.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECerebrovascular Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EArrhythmias\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EThrombotic Disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EApixaban is an oral factor Xa inhibitor with prompt onset and offset of anticoagulation, twice-a-day dosing, and no need for coagulation monitoring. Greg Flaker, MD, University of Missouri, Columbia, Missouri, USA, discussed the efficacy and safety of apixaban compared with warfarin in the Apixaban for the Prevention of Stroke in Subjects with Atrial Fibrillation trial [ARISTOTLE; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00412984\u0026amp;atom=%2Fspmdc%2F12%2F6%2F19.atom\u0022\u003ENCT00412984\u003C\/a\u003E] and compared with aspirin in the Apixaban Versus Acetylsalicylic Acid to Prevent Strokes trial [AVERROES; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00496769\u0026amp;atom=%2Fspmdc%2F12%2F6%2F19.atom\u0022\u003ENCT00496769\u003C\/a\u003E].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EIn the ARISTOTLE trial [Granger CB et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011], 18,201 patients with atrial fibrillation (AF) and at least 1 additional risk factor for stroke were randomly assigned to treatment with apixaban 5 mg BID or warfarin (target INR 2\u20133). The primary outcome was stroke or systemic embolism (SE). The median duration of follow-up was 1.8 years.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe rate of stroke or SE was significantly lower with apixaban (1.27% per year) versus warfarin (1.60% per year), with a 21% relative risk reduction (RRR) in the apixaban group (HR, 0.79; 95% CI, 0.66 to 0.95; p=0.011). Event rates per year were significantly lower with apixaban versus warfarin for hemorrhagic stroke (0.24% vs 0.47%; p\u0026lt;0.001) and all-cause death (3.52% vs 3.94%; p=0.047) but not for ischemic (or uncertain) stroke, SE, or myocardial infarction (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). Patients who were treated with apixaban had significantly lower rates of major bleeding (HR, 0.69; 95% CI, 0.60 to 0.80; p\u0026lt;0.001) and any bleeding (HR, 0.71; 95% CI, 0.68 to 0.75; p\u0026lt;0.001).\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\/14319\/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\/14319\/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\/14319\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-5\u0022 class=\u0022first-child\u0022\u003EEfficacy Outcomes.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EIn the AVERROES trial, 5600 patients with AF were randomly assigned to apixaban 5 mg BID or aspirin 81 to 324 mg\/day. The primary outcome was stroke or SE. Compared with aspirin, apixaban significantly reduced the risk of stroke or SE (RR, 0.46; 95% CI, 0.33 to 0.64; p\u0026lt;0.001). There was no significant difference in major bleeding risk with apixaban versus aspirin.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EDr. Flaker concluded that compared with warfarin, apixaban reduces stroke and SE, major bleeding, and mortality. Compared with aspirin, apixaban reduces stroke and SE and has comparable rates of major bleeding and tolerability.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EAnticoagulant Selection for Patients with AF\u003C\/h2\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EPeter R. Kowey, MD, Jefferson Medical College, Philadelphia, Pennsylvania, USA, discussed the challenge of choosing anticoagulation therapy for patients with AF. Warfarin is highly effective for this indication but has a narrow therapeutic target, frequent food and drug interactions, genetically determined metabolism, bridging issues, and a high rate of intracerebral and gastrointestinal bleeding and is difficult to reverse.\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EAlthough studies [Hart RG et al. \u003Cem\u003EAnn Intern Med\u003C\/em\u003E 2007] have demonstrated the efficacy of warfarin to prevent stroke in patients with AF, reducing stroke incidence by about 64%, many AF patients do not receive warfarin. A literature review [Bungard TJ et al. \u003Cem\u003EArch Intern Med\u003C\/em\u003E 2000] identified several barriers, including physicians\u0027 perceptions that 1) the risk of warfarin therapy is greater than the benefit; 2) patients are unreliable; and 3) maintaining therapeutic INR is difficult. Physicians also believe patients will refuse therapy, and they consider monitoring therapy inconvenient.\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EA number of therapies are under development (\u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E). The Randomized Evaluation of Long-Term Anticoagulant Therapy with Dabigatran Etexilate trial [RE-LY; Connolly SJ et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009] randomly assigned patients with AF and at least 1 additional risk factor to warfarin (INR, 2.0\u20133.0; n=6000), dabigatran etexilate (110 mg BID; n=6000), or dabigatran etexilate (150 mg BID; n=6000). Dabigatran 110 mg was noninferior to warfarin (p\u0026lt;0.001), and dabigatran 150 mg was superior to warfarin (p\u0026lt;0.001) for reduction of stroke and SE. Patients who were taking dabigatran 110 mg had significantly lower rates of major bleeding (p=0.003) and intracranial hemorrhage (p\u0026lt;0.001) versus patients who taking warfarin.\u003C\/p\u003E\n         \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\/14321\/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\/14321\/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\/14321\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-13\u0022 class=\u0022first-child\u0022\u003EEmerging Anticoagulants in AF.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EThe Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonist for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET; Patel MR et al \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011] demonstrated the noninferiority of rivaroxaban for reducing the rate of stroke and non-CNS embolism (HR, 0.79; 95% CI, 0.66 to 0.96; p\u0026lt;0.001). Apixaban was shown to significantly reduce cumulative risk of stroke or SE versus aspirin in the AVERROES trial (p\u0026lt;0.001). In the ARISTOTLE trial, apixaban was superior to warfarin for reducing the rate of stroke or SE (p=0.011). The factor Xa direct inhibitor edoxaban is currently undergoing investigation versus warfarin in the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation Thrombolysis in Myocardial Infarction trial [ENGAGE AF-TIMI 48; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00781391\u0026amp;atom=%2Fspmdc%2F12%2F6%2F19.atom\u0022\u003ENCT00781391\u003C\/a\u003E].\u003C\/p\u003E\n         \u003Cp id=\u0022p-16\u0022\u003ENew anticoagulants present several clinical challenges. For example, therapeutic ranges have not been established, no validated tests exist to measure anticoagulation effect, and there are no antidotes for most agents. In addition, compliance assessment is more difficult with these agents than with vitamin K antagonists, and the potential exists for unknown long-term adverse events. Balancing cost against efficacy is another challenge, and there are no head-to-head studies that have compared new agents. In the absence of head-to-head trials, the choice of agent must be based on trial data and a patient\u0027s profile.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 MD Conference Express\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\/6\/19.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?nzndtd\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?nzndtd\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}