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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\u003EDespite the increasing prevalence of atrial fibrillation (AF), no reliable method to detect AF in asymptomatic individuals has been established. This diagnostic uncertainty poses a challenge in implementing important treatment decisions, such as rate versus rhythm control and the need for anticoagulation in asymptomatic patients [Eitel C et al. Europace 2011].\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\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EDespite the increasing prevalence of atrial fibrillation (AF), no reliable method to detect AF in asymptomatic individuals has been established. This diagnostic uncertainty poses a challenge in implementing important treatment decisions, such as rate versus rhythm control and the need for anticoagulation in asymptomatic patients [Eitel C et al. Europace 2011]. Gerhard Hindricks, MD, PhD, University of Leipzig, Leipzig, Germany, discussed new developments in the diagnosis of AF.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ETo address limitations of current methods, researchers are pursuing two promising approaches: 1) implantable loop recorders (ILRs) and other monitoring technologies and 2) substrate analysis as a potential basis for individualized therapy.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ENew ILR Technologies\u003C\/h2\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EAdvances are being made in implantable cardiac monitors with dedicated AF detection algorithms. They detect AF via R-R variability pattern recognition. In the Xpect Trial, the AF burden that was measured with the implantable cardiac monitor (ICM) was correlated very well with the reference value that was derived from the Holter monitor (Pearson coefficient=0.97). The overall accuracy of the ICM for detecting AF was 98.5% [Hindricks G et al. \u003Cem\u003ECirc Arrhythm Electrophysiol\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EProf. Hindricks explained that ILR for AF detection is currently limited by a lack of data that support efficacy, including: no direct comparison to external monitoring techniques, no proof that ILRs are superior to existing methods for AF detection, the inability to identify patient populations that may benefit from ILRs, and the absence of scientific evidence that ILRs may improve either quality of life or hard AF-related clinical outcome parameters (reduced stroke risk).\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EThe quest to meet these challenges has led to the development of new technologies for ILRs. These devices automatically detect arrhythmias, store arrhythmia waveforms for visual confirmation, and sense from multiple electrodes. They include patient-triggered ECG storage and are tele-monitoring-enabled (a wireless global system without patient interaction; and transmission of ECG waveforms and detection statistics).\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EInjectable devices are another new technology. These units constitute less than 10% of current device volume, and provide up to 2 years of full-coverage ILRs. The new single-use external monitors for AF detection provide 14 days of continuous monitoring on one channel versus three channels that are combined into a single output in IRLs.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ETechnologies to Identify AF Substrate\u003C\/h2\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EMagnetic resonance imaging (MRI) is a promising modality for substrate identification. The quality of substrate analysis depends on the ability of MRI to enable detection of left atrial fibrosis, a finding that is associated with AF. This approach may lead to a better understanding of the stage of atrial disease in individual patients. New technologies that are focused on better characterization of atrial fibrosis include delayed-enhancement magnetic resonance imaging (DE-MRI) [Oakes RS et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2009; Badger TJ et al. \u003Cem\u003ECirc Arrhythm Electrophysiol\u003C\/em\u003E 2010] and late gadolinium enhancement-magnetic resonance imaging (LGE-MRI) [Vergara GR, Marrouche NF. \u003Cem\u003EJ Cardiovasc Electrophysiol\u003C\/em\u003E 2011].\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EOral Anticoagulant Treatment Innovations\u003C\/h2\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EAF is a common cause of ischemic stroke and transient ischemic attack (TIA) [Rizos T et al. \u003Cem\u003ECerebrovasc Dis\u003C\/em\u003E 2011]. Approximately 1% of the population is affected by AF, and its prevalence is growing with the aging population [Font MA et al. \u003Cem\u003EStroke Res Treat 2011].\u003C\/em\u003E Lars Wallentin, MD, PhD, Uppsala Clinical Research Center, Uppsala, Sweden, discussed new antithrombotic therapies to prevent stroke in AF.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EOral anticoagulants (OACs) are highly effective in reducing stroke in patients with AF, yet continuous OAC is prescribed for less than half of patients with AF who have risk factors for cardioembolism and no contraindications for anticoagulation [Font MA et al. \u003Cem\u003EStroke Res Treat\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EWarfarin and related oral vitamin K antagonists (VKAs) are the most widely used treatment for thromboembolic prevention in AF. VKA therapy, however, is associated with significant drawbacks, including the need for routine monitoring, numerous drug-drug and food-drug interactions, and risk of intracranial hemorrhage. Newer oral anticoagulants that inhibit factor IIa (eg, dabigatran) and factor Xa (eg, rivaroxaban, apixaban, edoxaban) appear to be safe and efficacious with important benefits, such as reduced risks of dangerous bleeding and no need for routine monitoring. Many novel anticoagulants are being developed that target various factors in the coagulation cascade.\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EThe two agents that are in the most advanced stages of development are dabigatran etexilate (approved in the United States, Europe, and Canada) [Connolly SJ et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009] and rivaroxaban [Patel MR et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011]. They inhibit thrombin and factor Xa, respectively. A recent Phase 3 study for the factor Xa inhibitor apixaban, also showed very promising results [Granger CB et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011]. Other agents that are in the early stages of development include several factor Xa inhibitors (betrixaban, darexaban, eribaxaban [PD 0348292], LY 517717, and TAK 442) and one thrombin inhibitor (AZD 0837) [Eriksson BI et al. \u003Cem\u003EClin Pharmacokinet\u003C\/em\u003E 2009].\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EThree large Phase 3 trials with factor Xa inhibitors have either been reported or are in progress: ROCKET AF (rivaroxaban), ARISTOTLE (apixaban), and ENGAGE-AF (edoxaban). All are double-blind, noninferiority studies, using warfarin as the comparator. The primary outcome is stroke or systemic embolism; the primary safety outcome is bleeding.\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EIn the ROCKET AF trial, the primary endpoint in the per-protocol cohort occurred in 188 patients in the rivaroxaban group (1.7% per year) and 241 patients in the warfarin group (2.2% per year; HR in the drug group, 0.79; 95% CI, 0.66 to 0.96; p\u0026lt;0.001 for noninferiority). However, when all events were included, whether the patients were on or off study drug (intention-to-treat cohort), there was no difference in the primary endpoint between rivaroxaban and warfarin (2.1% per year vs 2.4% per year; p=0.12). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 patients in the warfarin group (14.5% per year; HR, 1.03; 95% CI, 0.96 to 1.11; p=0.44), with significant reductions in intracranial hemorrhage (0.5% vs 0.72%; p=0.02) and fatal bleeding (0.2% vs 0.5%; p=0.003) in the rivaroxaban versus warfarin groups, respectively. The authors concluded that there was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred with less frequency in the rivaroxaban group [Patel MR. et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EWith apixaban (ARISTOTLE), the rate of the primary outcome was significantly reduced \u22121.27% per year versus 1.60% per year in the warfarin group (HR with apixaban, 0.79; 95% CI, 0.66 to 0.95; p\u0026lt;0.001 for noninferiority; p=0.01 for superiority) in the intention-to-treat analysis. The rate of major bleeding was also reduced with apixaban \u22122.13% per year versus 3.09% per year in the warfarin group (HR, 0.69; 95% CI, 0.60 to 0.80; p\u0026lt;0.001). Furthermore, apixaban was the first novel anticoagulant to reduce overall mortality in AF (3.52% versus 3.94%, HR, 0.89; 95% CI, 0.80 to 0.99; p=0.047). While the rate of hemorrhagic stroke was substantially reduced with apixaban (0.24% per year versus 0.47% per year in the warfarin group, HR, 0.51; 95% CI, 0.35 to 0.75; p\u0026lt;0.001), there was no difference in the rate of ischemic or uncertain type of stroke (0.97% per year in the apixaban group and 1.05% per year in the warfarin group; HR, 0.92; 95% CI, 0.74 to 1.13; p=0.42) [Granger CB et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-16\u0022\u003EProf. Wallentin ended his presentation by noting that the three new anticoagulants that have completed Phase 3 studies (dabigatran, rivaroxaban, apixaban) show promising efficacy and excellent safety compared with warfarin in patients with AF. Currently, only dabigatran has been approved for use in AF; the other two are being reviewed by regulatory authorities around the world. Future drug choice will depend on the careful weighing of risks versus benefits. Other factors to take into account include drug - specific issues, such as clearance, side effects, survival, patient preferences, and health economics.\u003C\/p\u003E\n      \u003C\/div\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\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\/31.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?nzmz8d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}