title: Atrial Premature Beats Predict Atrial Fibrillation in Cryptogenic Stroke: Results From the EMBRACE Trial The Relationship Between Daily Atrial Tachyarrhythmia Burden From Implantable Device Diagnostics and Stroke Risk: The TRENDS Study Health-related quality of life after myocardial infarction, does choice of method make a difference? Impact of Spontaneous Extracranial Bleeding Events on Health State Utility in Patients with Atrial Fibrillation: Results from the ENGAGE AF‐TIMI 48 Trial Subclinical atrial fibrillation in patients with recent transient ischemic attack A single European currency for EQ-5D health states Long-Term Treatment with Citicoline Prevents Cognitive Decline and Predicts a Better Quality of Life after a First Ischemic Stroke Uncovering Atrial Fibrillation Beyond Short-Term Monitoring in Cryptogenic Stroke Patients: Three-Year Results From the Cryptogenic Stroke and Underlying Atrial Fibrillation Trial Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF Quality of life after intracerebral hemorrhage: results of the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial. Performance of a New Leadless Implantable Cardiac Monitor in Detecting and Quantifying Atrial Fibrillation Results of the XPECT Trial Atrial fibrillation and the risk of myocardial infarction. Long-term risk of recurrent stroke after a first-ever stroke. The Oxfordshire Community Stroke Project. Cost-effectiveness of apixaban versus other new oral anticoagulants for stroke prevention in atrial fibrillation. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial Are the modified “simple questions” a valid and reliable measure of health related quality of life after stroke? Cost-effectiveness of an insertable cardiac monitor to detect atrial fibrillation in patients with cryptogenic stroke US Valuation of the EQ-5D Health States: Development and Testing of the D1 Valuation Model Safety Profile of a Miniaturized Insertable Cardiac Monitor: Results from Two Prospective Trials. Total atrial conduction time to predict occult atrial fibrillation after cryptogenic stroke Impact of disability status on ischemic stroke costs in Canada in the first year. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial Cryptogenic Stroke and underlying Atrial Fibrillation (CRYSTAL AF): design and rationale. Prevalence and Risk Factors for Paroxysmal Atrial Fibrillation and Flutter Detection after Cryptogenic Ischemic Stroke. Cost-effectiveness of apixaban vs. current standard of care for stroke prevention in patients with atrial fibrillation Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? Performance of a new atrial fibrillation detection algorithm in a miniaturized insertable cardiac monitor: Results from the Reveal LINQ Usability Study. Cryptogenic stroke and underlying atrial fibrillation. BioMonitor 2 Pilot Study: Early Experience With Implantation of the Biotronik BioMonitor 2 Implantable Cardiac Monitor. Valuation of EQ-5D health states in Poland: first TTO-based social value set in Central and Eastern Europe. A cross-sectional study of quality of life in an elderly population (75 years and over) with atrial fibrillation: secondary analysis of data from the Birmingham Atrial Fibrillation Treatment of the Aged study. The BioMonitor 2 insertable cardiac monitor: Clinical experience with a novel implantable cardiac monitor. Prevalence of atrial fibrillation with insertable cardiac monitors in cryptogenic stroke: A single-center experience. Detection of atrial fibrillation in patients with embolic stroke of undetermined source by prolonged monitoring with implantable loop recorders.
abstract: Background and Purpose — Many ischemic strokes or transient ischemic attacks are labeled cryptogenic but may have undetected atrial fibrillation ( AF ) . We sought to identify those most likely to have sub clinical AF . Methods — We prospect ively studied patients with cryptogenic stroke or transient ischemic attack aged ≥55 years in sinus rhythm , without known AF , enrolled in the intervention arm of the 30 Day Event Monitoring Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event ( EMBRACE ) trial . Participants underwent baseline 24-hour Holter ECG poststroke ; if AF was not detected , they were r and omly assigned to 30-day ECG monitoring with an AF auto-detect external loop recorder . Multivariable logistic regression assessed the association between baseline variables ( Holter-detected atrial premature beats [ APBs ] , runs of atrial tachycardia , age , and left atrial enlargement ) and subsequent AF detection . Results — Among 237 participants , the median baseline Holter APB count/24 h was 629 ( interquartile range , 142–1973 ) among those who subsequently had AF detected versus 45 ( interquartile range , 14–250 ) in those without AF ( P<0.001 ) . APB count was the only significant predictor of AF detection by 30-day ECG ( P<0.0001 ) , and at 90 days ( P=0.0017 ) and 2 years ( P=0.0027 ) . Compared with the 16 % overall 90-day AF detection rate , the probability of AF increased from < 9 % among patients with < 100 APBs/24 h to 9 % to 24 % in those with 100 to 499 APBs/24 h , 25 % to 37 % with 500 to 999 APBs/24 h , 37 % to 40 % with 1000 to 1499 APBs/24 h , and 40 % beyond 1500 APBs/24 h. Conclusions — Among older cryptogenic stroke or transient ischemic attack patients , the number of APBs on a routine 24-hour Holter ECG was a strong dose-dependent independent predictor of prevalent sub clinical AF . Those with frequent APBs have a high probability of AF and represent ideal c and i date s for prolonged ECG monitoring for AF detection . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00846924 Background —It is unknown if brief episodes of device-detected atrial fibrillation ( AF ) increase thromboembolic event ( TE ) risk . Methods and Results —TRENDS was a prospect i ve , observational study enrolling patients with ≥1 stroke risk factor ( heart failure , hypertension , age ≥65 years , diabetes , or prior TE ) receiving pacemakers or defibrillators that monitor atrial tachycardia (AT)/AF burden ( defined as the longest total AT/AF duration on any given day during the prior 30-day period ) . This time-varying exposure was up date d daily during follow-up and related to TE risk . Annualized TE rates were determined according to AT/AF burden subsets : zero , low ( < 5.5 hours [ median duration of subsets with nonzero burden ] ) , and high ( ≥5.5 hours ) . A multivariate Cox model provided hazard ratios including terms for stroke risk factors and time-varying AT/AF burden and antithrombotic therapy . Patients ( n=2486 ) had at least 30 days of device data for analysis . During a mean follow-up of 1.4 years , annualized TE risk ( including transient ischemic attacks ) was 1.1 % for zero , 1.1 % for low , and 2.4 % for high burden subsets of 30-day windows . Compared with zero burden , adjusted hazard ratios ( 95 % CIs ) in the low and high burden subsets were 0.98 ( 0.34 to 2.82 , P=0.97 ) and 2.20 ( 0.96 to 5.05 , P=0.06 ) , respectively . Conclusions —The TE rate was low compared with patients with traditional AF with similar risk profiles . The data suggest that TE risk is a quantitative function of AT/AF burden . AT/AF burden ≥5.5 hours on any of 30 prior days appeared to double TE risk . Additional studies are needed to more precisely investigate the relationship between stroke risk and AT/AF burden Abstract Objectives . The aim of this study was to compare health-related quality of life ( HRQoL ) scores obtained from the instrument Short Form (SF)-36 through the so-called SF-6D utilities , and those obtained from 15D , in patients with ST-elevation myocardial infa rct ion ( STEMI ) , and to evaluate the consequences in estimation of quality adjusted life years ( QALYs ) . Design . This was a sub- study of the Norwegian District Treatment of STEMI , in which patients with STEMI treated with tenecteplase , were r and omized to early angioplasty or st and ard management ( n = 266 ) .  HRQoL data were collected at all visits ( 0 , 1 , 3 , 7 and 12 months ) . All patients with complete data were included ( n = 248 ) . Results . The score range was 0.33–1.0 for SF-6D and 0.49–1.0 for 15D  . Mean utility scores from 15D were higher and had different distribution compared to scores from SF-6D . Mean QALY for the whole group was higher using 15D than SF-6D ( 0.89 vs. 0.77 ) . The incremental number of QALYs with early angioplasty compared to st and ard treatment was 0.005 ( 95 % CI : − 0.018 to 0.028 ) using SF-6D , and 0.004 ( 95 % CI : − 0.010 to 0.018 ) using the 15D instrument . Conclusions . Choice of instrument may influence HRQoL scores , but not necessarily the gain in QALYs Background The impact of different types of extracranial bleeding events on health‐related quality of life and health‐state utility among patients with atrial fibrillation is not well understood . Methods and Results The ENGAGE AF‐TIMI 48 ( Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation – Thrombolysis in Myocardial Infa rct ion 48 ) Trial compared edoxaban with warfarin with respect to the prevention of stroke or systemic embolism in atrial fibrillation . Data from the EuroQol‐5D ( EQ‐5D‐3L ) question naire , prospect ively collected at 3‐month intervals for up to 48 months , were used to estimate the impact of different categories of bleeding events on health‐state utility over 12 months following the event . Longitudinal mixed‐effect models revealed that major gastrointestinal bleeds and major nongastrointestinal bleeds were associated with significant immediate decreases in utility scores ( −0.029 [ −0.044 to −0.014 ; P<0.001 ] and −0.029 [ −0.046 to −0.012 ; P=0.001 ] , respectively ) . These effects decreased in magnitude over time , and were no longer significant for major nongastrointestinal bleeds at 9 months , but remained borderline significant for major gastrointestinal bleeds at 12 months . Clinical ly relevant nonmajor and minor bleeds were associated with smaller but measurable immediate impacts on utility ( −0.010 [ −0.016 to −0.005 ] and −0.016 [ −0.024 to −0.008 ] ; P<0.001 for both ) , which remained relatively constant and statistically significant over the 12 months following the bleeding event . Conclusions All categories of bleeding events were associated with negative impacts on health‐state utility  in patients with atrial fibrillation . Major bleeds were associated with relatively large immediate decreases in utility scores that gradually diminished over 12 months ; clinical ly relevant nonmajor and minor bleeds were associated with smaller immediate decreases in utility that persisted over 12 months . Clinical Trial Registration URL : https://www . clinical trials.gov/. Unique identifier : NCT00781391 BACKGROUND Atrial fibrillation ( AF ) is a major risk factor of stroke , but the association between AF and transient ischemic attack ( TIA ) is less clear . Despite this , patients with TIA are included in stroke trials . AIMS To determine the 1-year incidence of AF in TIA patients using an insertable cardiac monitor ( ICM ) ; second , to determine factors associated with incident AF in these patients . METHODS Prospect i ve cohort study of patients with TIA with normal st and ard electrocardiogram ( ECG ) and 72-hour Holter monitoring ( HM ) . Exclusion criteria were as follows : age < 18 or > 81 years ; prior AF/stroke ; ongoing oral anticoagulation therapy or contraindication for it ; significant carotid artery stenosis ; uncertain TIA diagnosis . Eligible patients received an ICM and were followed for 12 months . RESULTS From November 2013 to October 2015 , 809 patients were diagnosed with TIA . In total , 235 patients were eligible . Nine ( 3.8 % ) of these had AF on st and ard ECG or HM . Of the remaining patients , 121 refused ICM implantation . In total , 105 patients ( median age 65.4 years [ range 27.1 - 80.8 ] , 46 % males ) received an ICM , which revealed AF in 7 ( 6.7 % ) . Factors associated with new-onset AF were a history of recurrent TIA ( odds ratio [ OR ] 11.5 , 95 % confidence interval [ CI ] 2.1 - 63.6 ) and heart failure ( OR 12.7 , 95 % CI 1.71 - 96.83 ) . CONCLUSIONS The 1-year incidence of AF in TIA patients with normal ECG and HM was 6.7 % using an ICM . Factors associated with development of AF were recurrent TIA and heart failure Abstract The EQ-5D question naire is a widely used generic instrument for describing and valuing health that was developed by the EuroQol Group . A primary objective of the EuroQol Group is the investigation of values for health states in the general population in different countries . As part of the EuroQol enterprise 11 population surveys were carried out in six Western European countries ( Finl and , Germany , The Netherl and s , Spain , Sweden and the UK ) to value health states as defined by the EQ-5D using a st and ardised visual analogue scale ( EQ-5D VAS ) . This contribution reports how a European set of general population preference weights was derived from the data collected in the 11 valuation studies . The scores from this set of preference weights can be applied to generate a VAS-based weighted health status index for all the potential 243 EQ-5D health states for use in multi-national studies . To estimate the preference weights a multi-level regression analysis was performed on 82,910 valuations of 44 EQ-5D health states elicited from 6,870 respondents . Stable and plausible solutions were found for the model parameters . The R2 value was 75 % . The analysis showed that the major source of variance , apart from ' r and om error ' , was variance between individuals ( 28.3 % of the total residual variance ) . These results suggest that VAS values for EQ-5D health states in six Western European countries can be described by a common model Stroke , as the leading cause of physical disability and cognitive impairment , has a very significant impact on patients ’ quality of life ( QoL ) . The objective of this study is to know the effect of citicoline treatment in Qol and cognitive performance in the long-term in patients with a first ischemic stroke . This is an open-label , r and omized , parallel study of citicoline vs. usual treatment . All subjects were selected 6 weeks after suffering a first ischemic stroke and r and omized into parallel arms . Neuropsychological evaluation was performed at 1 month , 6 months , 1 year and 2 years after stroke , and QoL was measured using the EuroQoL-5D question naire at 2 years . 163 patients were followed during 2 years . The mean age was 67.5 years-old , and 50.9 % were women . Age and absence of citicoline treatment were independent predictors of both utility and poor quality of life .  Patients with cognitive impairment  had a poorer QoL at 2 years ( 0.55 vs. 0.66 in utility , p = 0.015 ) . Citicoline treatment improved significantly cognitive status during follow-up ( p = 0.005 ) . In conclusion , treatment with long-term citicoline is associated with a better QoL and improves cognitive status 2 years after a first ischemic stroke Background —Atrial fibrillation ( AF ) can be a cause of previously diagnosed cryptogenic stroke . However , AF can be paroxysmal and asymptomatic , thereby making detection with routine ECG methods difficult . Oral anticoagulation is highly effective in reducing recurrent stroke in patients with AF , but its initiation is dependent on the detection of AF . Cryptogenic Stroke and Underlying Atrial Fibrillation ( CRYSTAL AF ) is the first r and omized study to report the detection of AF in cryptogenic stroke patients using continuous long-term monitoring via insertable cardiac monitors ( ICM ) . Methods and Results — Patients with prior cryptogenic stroke were r and omized to control ( n=220 ) or ICM ( n=221 ) and followed for ⩽36 months . Cumulative AF detection rates in the ICM arm increased progressively during this period ( 3.7 % , 8.9 % , 12.4 % , and 30.0 % at 1 , 6 , 12 , and 36 months , respectively ) , but remained low in the control arm ( 3.0 % at 36 months ) . This result ed in oral anticoagulation prescription in 94.7 % of ICM patients with AF detected at 6 months , 96.6 % at 12 months , and 90.5 % at 36 months . Among ICM patients with AF detected , the median time to AF detection was 8.4 months , 81.0 % of first AF episodes were asymptomatic , and 94.9 % had at least 1 day with > 6 minutes of AF . Conclusions —Three-year monitoring by ICM in cryptogenic stroke patients demonstrated a significantly higher AF detection rate compared with routine care . Given the frequency of asymptomatic first episodes and the long median time to detection , these findings highlight the limitations of using traditional AF detection methods . The majority of patients with AF were prescribed oral anticoagulation therapy . Clinical Trial Registration — Clinical trials.gov ; Unique identifier : NCT00924638 BACKGROUND In the AVERROES study , apixaban , a novel factor Xa inhibitor , reduced the risk of stroke or systemic embolism in patients with atrial fibrillation who were at high risk of stroke but unsuitable for vitamin K antagonist therapy . We aim ed to investigate whether the subgroup of patients with previous stroke or transient ischaemic attack ( TIA ) would show a greater benefit from apixaban compared with aspirin than would patients without previous cerebrovascular events . METHODS In AVERROES , 5599 patients ( mean age 70 years ) with atrial fibrillation who were at increased risk of stroke and unsuitable for vitamin K antagonist therapy were r and omly assigned to receive apixaban ( 5 mg twice daily ) or aspirin ( 81 - 324 mg per day ) . The mean follow-up was 1·1 years . The primary efficacy outcome was stroke or systemic embolism ; the primary safety outcome was major bleeding . Patients and investigators were masked to study treatment . In this prespecified subgroup analysis , we used Kaplan-Meier estimates of 1-year event risk and Cox proportional hazards regression models to compare the effects of apixaban in patients with and without previous stroke or TIA . AVERROES is registered at Clinical Trials.gov , number NCT00496769 . FINDINGS In patients with previous stroke or TIA , ten events of stroke or systemic embolism occurred in the apixaban group ( n=390 , cumulative hazard 2·39 % per year ) compared with 33 in the aspirin group ( n=374 , 9·16 % per year ; hazard ratio [ HR ] 0·29 , 95 % CI 0·15 - 0·60 ) . In those without previous stroke or TIA , 41 events occurred in the apixaban group ( n=2417 , 1·68 % per year ) compared with 80 in the aspirin group ( n=2415 , 3·06 % per year ; HR 0·51 , 95 % CI 0·35 - 0·74 ) . The p value for interaction of the effects of aspirin and apixaban with previous cerebrovascular events was 0·17 . Major bleeding was more frequent in patients with history of stroke or TIA than in patients without ( HR 2·88 , 95 % CI 1·77 - 4·55 ) but risk of this event did not differ between treatment groups . INTERPRETATION In patients with atrial fibrillation  , apixaban is similarly effective whether or not patients have had a previous stroke or TIA . Given that those with previous stroke or TIA have a higher risk of stroke , the absolute benefits might be greater in these patients . FUNDING Bristol-Myers Squibb and Pfizer BACKGROUND In ROCKET AF , rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation ( AF ) . We aim ed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack ( TIA ) . METHODS In ROCKET AF , patients with AF who were at increased risk of stroke were r and omly assigned ( 1:1 ) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin ( international normalised ratio 2·0 - 3·0 ) . Patients and investigators were masked to treatment allocation . Between Dec 18 , 2006 , and June 17 , 2009 , 14 264 patients from 1178 centres in 45 countries were r and omly assigned . The primary endpoint was the composite of stroke or non-CNS systemic embolism . In this sub study we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA . Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population . ROCKET AF is registered with Clinical Trials.gov , number NCT00403767 . FINDINGS 7468 ( 52 % ) patients had a previous stroke ( n=4907 ) or TIA ( n=2561 ) and 6796 ( 48 % ) had no previous stroke or TIA .  The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA ( 2·79 % rivaroxaban vs 2·96 % warfarin ; hazard ratio [ HR ] 0·94 , 95 % CI 0·77 - 1·16 ) and those without ( 1·44%vs 1·88 % ; 0·77 , 0·58 - 1·01 ; interaction p=0·23 ) . The number of major and non-major clinical ly relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA ( 13·31 % rivaroxaban vs 13·87 % warfarin ; HR 0·96 , 95 % CI 0·87 - 1·07 ) and those without ( 16·69%vs 15·19 % ; 1·10 , 0·99 - 1·21 ; interaction p=0·08 ) . INTERPRETATION There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA . These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF . FUNDING Johnson and Johnson Pharmaceutical Research and Development and Bayer HealthCare BACKGROUND AND PURPOSE Neurological impairment and physical disability are frequent and important complications of stroke with serious consequences for health-related quality of life ( HRQOL ) . Little data exist , however , on the risk factors for poor HRQOL after intracerebral hemorrhage , the deadliest and most disabling form of stroke . METHODS  Factor Seven for Acute Hemorrhagic Stroke ( FAST ) was an international , r and omized , double-blind , placebo-controlled trial conducted between May 2005 and February 2007 at 122 sites in 22 countries . All patients were followed for 3 months after stroke onset and HRQOL was assessed using the EuroQoL. Multivariate stepwise logistic regression was used to identify predictors of poor HRQOL based on demographic and clinical baseline characteristics and in-hospital complications . RESULTS Six hundred fifty-seven patients survived until 3 months after stroke onset , and 621 ( 95 % ) completed the EuroQoL. Two percent had a utility score < 0 ( HRQOL worse than death ) , 15 % a utility score < 0.2 , 32 % a utility score < 0.5 , and 87 % a score < 0.87 ( average score in the general population ) . At the other end of the scale , 13 % had a utility score of 1 ( perfect HRQOL ) . Independent predictors of poor HRQOL were advanced age ( OR , 1.80 ; P<0.0001 ) , higher baseline National Institutes of Health Stroke Scale score ( OR , 1.11 ; P<0.0001 ) , higher systolic blood pressure ( OR , 1.05 ; P=0.0039 ) , higher baseline intracerebral hemorrhage volume ( OR , 1.11 ; P=0.015 ) , deep ( versus lobar ) hematoma location ( OR , 3.05 ; P=0.003 ) , and increase in neurological deficit in first 72 hours after ICH onset ( Delta Glasgow Coma Scale > or=2 or Delta National Institutes of Health Stroke Scale > or=4 ; OR , 2.04 ; P=0.006 ) . The model explained a large amount of the variation in the utility score ( C-statistic 0.77 ) . CONCLUSIONS The vast majority of survivors after intracerebral hemorrhage have very poor HRQOL . Critical care interventions design ed to control blood pressure or prevent neuroworsening may improve HRQOL in intracerebral hemorrhage survivors Background —Current methods for detecting atrial fibrillation ( AF ) have limited diagnostic yield . Continuous monitoring with automatic arrhythmia detection and classification may improve detection of symptomatic and asymptomatic AF and subsequent patient treatment . The study purpose was to quantify the performance of the first implantable leadless cardiac monitor ( ICM ) with dedicated AF detection capabilities . Methods and Results — Patients ( n=247 ) with an implanted ICM ( Reveal XT , Medtronic Inc , Minneapolis , Minn ) who were likely to present with paroxysmal AF were selected . A special Holter device stored 46 hours of subcutaneously recorded ECG , ICM markers , and 2 surface ECG leads . The ICM  automatic arrhythmia classification was compared with the core laboratory classification of the surface ECG . Of the 206 analyzable Holter recordings collected , 76 ( 37 % ) contained at least 1 episode of core laboratory classified AF . The sensitivity , specificity , positive predictive value , and negative predictive value for identifying patients with any AF were 96.1 % , 85.4 % , 79.3 % , and 97.4 % , respectively . The AF burden measured with the ICM was very well correlated with the reference value derived from the Holter ( Pearson coefficient=0.97 ) . The overall accuracy of the ICM for detecting AF was 98.5 % . Conclusions —In this ICM validation study , the dedicated AF detection algorithm reliably detected the presence or absence of AF and the AF burden was accurately quantified . The ICM is a promising new diagnostic and monitoring tool for the clinician to treat AF patients independently of symptoms . Long-term studies are needed to evaluate the clinical benefits of the technology . Clinical Trial Registration — clinical trials.gov Identifier NCT00680927 IMPORTANCE Myocardial infa rct ion ( MI ) is an established risk factor for  atrial fibrillation ( AF ) .  However , the extent to which AF is a risk factor for MI has not been investigated . OBJECTIVE To examine the risk of incident MI associated with AF . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve cohort of 23,928 participants residing in the continental United States and without coronary heart disease at baseline were enrolled from the Reasons for Geographic and Racial Differences in Stroke ( REGARDS ) cohort between 2003 and 2007 , with follow-up through December 2009 . MAIN OUTCOMES AND MEASURES Expert-adjudicated total MI events ( fatal and nonfatal ) . RESULTS Over 6.9 years of follow-up ( median 4.5 years ) , 648 incident MI events occurred . In a sociodemographic-adjusted model , AF was associated with about 2-fold increased risk of MI ( hazard ratio [ HR ] , 1.96 [ 95 % CI , 1.52 - 2.52 ] ) . This association remained significant ( HR , 1.70 [ 95 % CI , 1.26 - 2.30 ] ) after further adjustment for total cholesterol , high-density lipoprotein cholesterol , smoking status , systolic blood pressure , blood pressure-lowering drugs , body mass index , diabetes , warfarin use , aspirin use , statin use , history of stroke and vascular disease , estimated glomerular filtration rate , albumin to creatinine ratio , and C-reactive protein level . In subgroup analysis , the risk of MI associated with AF was significantly higher in women ( HR , 2.16 [ 95 % CI , 1.41 - 3.31 ] ) than in men ( HR , 1.39 [ 95 % CI , 0.91 - 2.10 ] ) and in blacks ( HR , 2.53 [ 95 % CI , 1.67 - 3.86 ] ) than in whites ( HR , 1.26 [ 95 % CI , 0.83 - 1.93 ] ) ; for interactions , P = .03 and P = .02 , respectively . On the other h and , there were no significant differences in the risk of MI associated with AF in older ( ≥75 years ) vs younger ( < 75 years ) participants ( HR , 2.00 [ 95 % CI , 1.16 - 3.35 ] and HR , 1.60 [ 95 % CI , 1.11 - 2.30 ] , respectively ) ; for interaction , P = .44 . CONCLUSIONS AND RELEVANCE AF is independently associated with an increased risk of incident MI , especially in women and blacks . These findings add to the growing concerns of the seriousness of AF as a public health burden : in addition to being a well-known risk factor for stroke , AF is also associated with increased risk of MI BACKGROUND AND PURPOSE There have been few community-based studies of long-term prognosis after acute stroke . This study aims to provide precise estimates of the absolute and relative risks of stroke recurrence in an unselected cohort of patients with a first-ever stroke . METHODS Six hundred seventy-five patients were registered in a community-based stroke register ( the Oxfordshire Community Stroke Project ) and prospect ively followed for up to 6.5 years .  Their relative risk of recurrent stroke was calculated using age- and sex-specific incidence rates for first stroke in Oxfordshire . RESULTS One hundred eighty recurrent episodes of stroke were identified , of which 135 were first recurrences . Given survival , the actuarial risk of suffering a recurrence was 30 % ( 95 % confidence interval , 20 % to 39 % ) by 5 years , about nine times the risk of stroke in the general population . The risk was highest early after the first stroke : 13 % ( 95 % confidence interval , 10 % to 16 % ) by 1 year , 15 times the risk in the general population . After the first year the average annual risk was about 4 % . The risk of stroke recurrence did not appear to be related to age or pathological type of stroke . CONCLUSIONS The absolute and relative risks of recurrent stroke are highest early after the first stroke but remain elevated for several years thereafter . Efforts at secondary prevention should be initiated as soon as possible and continued for several years to gain greatest benefit BACKGROUND Apixaban ( 5 mg BID ) , dabigatran ( available as 150 mg and 110 mg BID in Europe ) , and rivaroxaban ( 20 mg once daily ) are 3 novel oral anticoagulants ( NOACs ) currently approved for stroke prevention in patients with atrial fibrillation ( AF ) . OBJECTIVE The objective of this study was to evaluate the cost-effectiveness of apixaban against other NOACs from the perspective of the United Kingdom National Health Services . METHODS A Markov model was developed to evaluate the pharmacoeconomic impact of apixaban versus other NOACs over a lifetime . Pair-wise indirect treatment comparisons were conducted against other NOACs by using ARISTOTLE ( Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation ) , RE-LY ( R and omized Evaluation of Long-Term Anticoagulation Therapy ) , and ROCKET-AF ( Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ) trial results for the following end points : ischemic stroke , hemorrhagic stroke , intracranial hemorrhage , other major bleeds , clinical ly relevant nonmajor bleeds , myocardial infa rct ion , and treatment discontinuations . Outcomes were life-years , quality -adjusted life years gained , direct health care costs , and incremental cost-effectiveness ratios . RESULTS Apixaban was projected to increase life expectancy versus other NOACs , including dabigatran ( both doses ) and rivaroxaban . A small increase in therapeutic management costs was observed with apixaban due to projected gains in life expectancy and lower discontinuation rates anticipated on apixaban versus other NOACs through lifetime . The estimated incremental cost-effectiveness ratio was £ 9611 , £ 4497 , and £ 5305 per quality -adjusted life-year gained with apixaban compared with dabigatran 150 mg BID , dabigatran 110 mg BID , and rivaroxaban 20 mg once daily , respectively . Sensitivity analyses indicated that results were robust over a wide range of inputs . CONCLUSIONS Although our analysis was limited by the absence of head-to-head trials , based on the indirect comparison data available , our model projects that apixaban may be a cost-effective alternative to dabigatran 150 mg BID , dabigatran 110 mg BID , and rivaroxaban 20 mg once daily for stroke prevention in AF patients from the perspective of the United Kingdom National Health Services BACKGROUND In the ARISTOTLE trial , the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation ( AF ) . Patients with AF and previous stroke or transient ischaemic attack ( TIA ) have a high risk of stroke . We therefore aim ed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA . METHODS Between Dec 19 , 2006 , and April 2 , 2010 , patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries . 18,201 patients with AF or atrial flutter were r and omly assigned to receive apixaban 5 mg twice daily or warfarin ( target international normalised ratio 2·0 - 3·0 ) . The median duration of follow-up was 1·8 years ( IQR 1·4 - 2·3 ) . The primary efficacy outcome was stroke or systemic embolism , analysed by intention to treat . The primary safety outcome was major bleeding in the on-treatment population . All participants , investigators , and sponsors were masked to treatment assignments . In this subgroup analysis , we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA . The ARISTOTLE trial is registered with Clinical Trials.gov , number NTC00412984 . FINDINGS Of the trial population , 3436 ( 19 % ) had a previous stroke or TIA . In the subgroup of patients with previous stroke or TIA , the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group ( hazard ratio [ HR ] 0·76 , 95 % CI 0·56 to 1·03 ) ; in the subgroup of patients without previous stroke or TIA , the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin ( HR 0·82 , 95 % CI 0·65 to 1·03 ; p for interaction=0·71 ) . The absolute reduction in the rate of stroke and systemic embolism  with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up ( 95 % CI -0·08 to 1·63 ) in patients with and 0·22 ( -0·03 to 0·47 ) in those without previous stroke or TIA . The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years ( 95 % CI 0·09 - 2·04 ) in patients with and 0·93 ( 0·54 - 1·32 ) in those without previous stroke or TIA . INTERPRETATION The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA . Owing to the higher risk of these outcomes in patients with previous stroke or TIA , the absolute benefits of apixaban might be greater in this population . FUNDING Bristol-Myers Squibb and Pfizer OBJECTIVES Two “ simple questions ” were developed as a minimalist measurement tool to assess outcome in large trials and epidemiological studies after stroke . A previous study of their validity had disclosed ambiguities in their wording . In this study , the clarity , validity , and reliability of a modified version of these simple questions were examined . The relation between patients ' responses to these questions and two widely used generic measures of health related quality of life were also studied . METHODS A hospital based stroke register cohort of 152 patients , who were all visited at home by a study nurse , was used to study validity . A cohort of 1753 patients derived from the International Stroke Trial was used to study the relation with measures of quality of life . The sensitivity , specificity , and accuracy with which responses to each question predicted the patients ' outcome measured using st and ard instruments was assessed . The distribution of scores for the EuroQol and SF-36 was examined for patients classified as dependent , independent , and fully recovered by the combined use of the modified simple questions . RESULTS The modified “ dependency ” question had excellent sensitivity ( > 85 % ) , specificity ( > 79 % ) , and accuracy ( > 82 % ) for identifying dependency after stroke . The “ problems ” question had good sensitivity ( 65–88 % ) and moderate specificity ( 36–72 % ) for the detection of problems in a broad range of domains . The combined use of the modified dependency and problems questions provided a valid , simple , and reliable overall indicator of health related quality of life after stroke . CONCLUSIONS The modified simple questions have excellent face validity and good measurement properties for the assessment of outcome after stroke . They are particularly well suited for large epidemiological studies and r and omised trials Background and aims Documentation of atrial fibrillation is required to initiate oral anticoagulation therapy for recurrent stroke prevention . Atrial fibrillation often goes undetected with traditional electrocardiogram monitoring techniques . We evaluated whether atrial fibrillation detection using continuous long-term monitoring with an insertable cardiac monitor is cost-effective for preventing recurrent stroke in patients with cryptogenic stroke , in comparison to the st and ard of care . Methods A lifetime Markov model was developed to estimate the cost-effectiveness of insertable cardiac monitors from a UK National Health Service perspective using data from the r and omized CRYSTAL-AF trial and other published literature . We also conducted scenario analyses ( CHADS2 score ) and probabilistic sensitivity analyses . All costs and benefits were discounted at 3.5 % . Results Monitoring cryptogenic stroke patients with an insertable cardiac monitor was associated with fewer recurrent strokes and increased quality -adjusted life years compared to the st and ard of care ( 7.37 vs 7.22 ) . Stroke-related costs were reduced in insertable cardiac monitor patients , but overall costs remained higher than the st and ard of care ( £ 19,631 vs £ 17,045 ) . The incremental cost-effectiveness ratio was £ 17,175 per quality -adjusted life years gained , compared to st and ard of care in the base-case scenario , which is below established quality -adjusted life years willingness-to-pay thresholds . When warfarin replaced non-vitamin-K oral anticoagulants as the main anticoagulation therapy , the incremental cost-effectiveness ratio was £ 13,296 per quality -adjusted life years gained . Conclusion Insertable cardiac monitors are a cost-effective diagnostic tool for the prevention of recurrent stroke in patients with cryptogenic stroke . The cost-effectiveness results have relevance for the UK and across value-based healthcare systems that assess costs relative to outcomes Purpose : The EQ-5D is a brief , multiattribute , preference-based health status measure . This article describes the development of a statistical model for generating US population -based EQ-5D preference weights . Methods : A multistage probability sample was selected from the US adult civilian noninstitutional population . Respondents valued 13 of 243 EQ-5D health states using the time trade-off ( TTO ) method . Data for 12 states were used in econometric modeling . The TTO valuations were linearly transformed to lie on the interval [ −1 , 1 ] . Methods were investigated to account for interaction effects caused by having problems in multiple EQ-5D dimensions . Several alternative model specifications ( eg , pooled least squares , r and om effects ) also were considered . A modified split- sample approach was used to evaluate the predictive accuracy of the models . All statistical analyses took into account the clustering and disproportionate selection probabilities inherent in our sampling design . Results : Our D1 model for the EQ-5D included ordinal terms to capture the effect of departures from perfect health as well as interaction effects . A r and om effects specification of the D1 model yielded a good fit for the observed TTO data , with an overall R2 of 0.38 , a mean absolute error of 0.025 , and 7 prediction errors exceeding 0.05 in absolute magnitude . Conclusions : The D1 model best predicts the values for observed health states . The result ing preference weight estimates represent a significant enhancement of the EQ-5D 's utility for health status assessment and economic analysis in the US BACKGROUND Insertable cardiac monitors ( ICMs ) are used to continuously monitor the patient 's electrocardiogram . In response to patient activation or based on automated device algorithms , arrhythmia episodes are stored and automatically transmitted daily to the clinician . Thus , ICMs can be used to diagnose arrhythmias in at-risk patients and in those with symptoms potentially attributable to arrhythmias . The ICM described in this report has undergone a dramatic change in size and method of insertion . METHODS To evaluate the safety profile of the ICM procedure , we analyzed procedure-related adverse events ( AEs ) from two separate trials : A controlled , nonr and omized multicenter study ( Reveal LINQ(TM ) Usability study ) and a multicenter registry ( Reveal LINQ(TM ) Registry ) evaluating real-world experience . For the Registry we reported all procedure-related AEs upon occurrence , whereas for the Usability study , we reported events occurring during the first month of follow-up . RESULTS The Usability study enrolled 151 patients ( age 56.6 ± 12.1 years ; male 67 % ) at 16 centers ; during follow-up , an infection was observed in 1.3 % patients and a procedure-related serious AE ( SAE ) in 0.7 % patients . The Registry enrolled 122 patients ( age 61.0 ± 17.8 years ; male 47 % ) at seven centers ; during follow-up , an infection was observed in 1.6 % patients and a procedure-related SAE in 1.6 % patients . CONCLUSIONS The cumulative experience from a controlled clinical trial and a " real-world " registry demonstrate that the new ICM can be inserted with very low incidence of AEs Background Insertable cardiac monitor ( ICM ) increases the detection rate of occult atrial fibrillation ( AF ) after cryptogenic stroke . The aim of this study was to evaluate the prognostic significance of  total atrial conduction time ( TACT )  assessed by tissue Doppler imaging ( PA-TDI interval ) to predict AF presence in patients with cryptogenic stroke . Methods Ninety patients ( 57.7 ± 12.3 years , 48 % women ) after acute cryptogenic stroke and ICM implantation were prospect i ve recruited at four centers for continuous rhythm monitoring . In all patients , TACT was measured by PA-TDI interval via echocardiography . Patients were followed up ( 331 ± 186 days ) for detection of AF ( defined by episode lasting ≥30 s ) . Results AF was detected in 16 patients ( 18 % ) during follow-up ( 331 ± 186 days ) . The median period to AF detection was 30 days ( q1–q3 ; 16–62 days ) . Patients who exhibited occult AF were characterized by significantly longer PA-TDI intervals ( 154.7 ± 12.6 vs. 133.9 ± 9.5 ms , p < 0.0001 ) . The cut-off value of PA-TDI interval at 145 ms demonstrated sensitivity and specificity for AF detection of 93.8 and 90.5 % , respectively . In multivariate analysis , CHA2DS2–VASc score ( HR 1.96 per 1 point , p < 0.01 ) and longer PA-TDI interval ( HR 4.05 per 10 ms , p < 0.0001 ) were independent predictors of occult AF . Conclusion Our data suggest that measurement of TACT could help to predict future AF detection in patients with cryptogenic stroke . The clinical importance of prolonged rhythm monitoring or indication of direct anticoagulation therapy after cryptogenic stroke based on TACT should be further investigated BACKGROUND Longitudinal , patient-level data on re source use and costs after an ischemic stroke are lacking in Canada . The objectives of this analysis were to calculate costs for the first year post-stroke and determine the impact of disability on costs . METHODOLOGY The Economic Burden of Ischemic Stroke ( BURST ) Study was a one-year prospect i ve study with a cohort of ischemic stroke patients recruited at 12 Canadian stroke centres . Clinical history , disability , health preference and re source utilization information was collected at discharge , three months , six months and one year . Re sources included  direct medical costs ( 2009 CAN$ ) such as emergency services , hospitalizations , rehabilitation , physician services , diagnostics , medications , allied health professional services , homecare , medical/assistive devices , changes to residence and paid caregivers , as well as indirect costs . Results were stratified by disability measured at discharge using the modified Rankin Score ( mRS ) : non-disabling stroke ( mRS 0 - 2 ) and disabling stroke ( mRS 3 - 5 ) . RESULTS We enrolled 232 ischemic stroke patients ( age 69.4 ± 15.4 years ; 51.3 % male ) and 113 ( 48.7 % ) were disabled at hospital discharge .  The average annual cost was $ 74,353 ; $ 107,883 for disabling strokes and $ 48,339 for non-disabling strokes . CONCLUSIONS An average annual cost for ischemic stroke was calculated in which a disabling stroke was associated with a two-fold increase in costs compared to NDS . Costs during the hospitalization to three months phase were the highest contributor to the annual cost . A " back of the envelope " calculation using 38,000 stroke admissions and the average annual cost yields $ 2.8 billion as the burden of ischemic stroke BACKGROUND Anticoagulants are more effective than antiplatelet agents at reducing stroke risk in patients with atrial fibrillation , but whether this benefit outweighs the increased risk of bleeding in elderly patients is unknown . We assessed whether warfarin reduced risk of major stroke , arterial embolism , or other intracranial haemorrhage compared with aspirin in elderly patients . METHODS 973 patients aged 75 years or over ( mean age 81.5 years , SD 4.2 ) with atrial fibrillation were recruited from primary care and r and omly assigned to warfarin ( target international normalised ratio 2 - 3 ) or aspirin ( 75 mg per day ) . Follow-up was for a mean of 2.7 years ( SD 1.2 ) . The primary endpoint was fatal or disabling stroke ( ischaemic or haemorrhagic ) , intracranial haemorrhage , or clinical ly significant arterial embolism . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N89345269 . FINDINGS There were 24 primary events ( 21 strokes , two other intracranial haemorrhages , and one systemic embolus ) in people assigned to warfarin and 48 primary events ( 44 strokes , one other intracranial haemorrhage , and three systemic emboli ) in people assigned to aspirin ( yearly risk 1.8%vs 3.8 % , relative risk 0.48 , 95 % CI 0.28 - 0.80 , p=0.003 ; absolute yearly risk reduction 2 % , 95 % CI 0.7 - 3.2 ) . Yearly risk of extracranial haemorrhage was 1.4 % ( warfarin ) versus 1.6 % ( aspirin ) ( relative risk 0.87 , 0.43 - 1.73 ; absolute risk reduction 0.2 % , -0.7 to 1.2 ) . INTERPRETATION These data support the use of anticoagulation therapy for people aged over 75 who have atrial fibrillation , unless there are contraindications or the patient decides that the benefits are not worth the inconvenience BACKGROUND In the R and omised Evaluation of Long-Term Anticoagulation Therapy ( RE-LY ) trial , dabigatran reduced occurrence of both stroke and haemorrhage compared with warfarin in patients who had atrial fibrillation and were at increased risk of stroke . We aim ed to assess the effects of dabigatran compared with warfarin in the subgroup of patients with previous stroke or transient ischaemic attack . METHODS In the RE-LY trial , 18,113 patients from 967 centres in 44 countries were r and omly assigned to 110 mg or 150 mg dabigatran twice daily or to warfarin dose adjusted to international normalised ratio 2·0 to 3·0 . Median follow-up was 2·0 years ( IQR 1·14 - 2·86 ) , and the primary outcome was stroke or systemic embolism . The primary safety outcome was major haemorrhage . Patients and investigators were aware of whether patients received warfarin or dabigatran , but not of dabigatran dose , and event adjudicators were masked to treatment . In a predefined analysis , we investigated the outcomes of the RE-LY trial in subgroups of patients with or without previous stroke or transient ischaemic attack . RE-LY is registered with Clinical Trials.gov , NCT00262600 . FINDINGS Within the subgroup of patients with previous stroke or transient ischaemic attack , 1195 patients were from the 110 mg dabigatran group , 1233 from the 150 mg dabigatran group , and 1195 from the  warfarin group . Stroke or systemic embolism occurred in 65 patients ( 2·78 % per year ) on warfarin compared with 55 ( 2·32 % per year ) on 110 mg dabigatran ( relative risk 0·84 , 95 % CI 0·58 - 1·20 ) and 51 ( 2·07 % per year ) on 150 mg dabigatran ( 0·75 , 0·52 - 1·08 ) . The rate of major bleeding was significantly lower in patients on 110 mg dabigatran ( RR 0·66 , 95 % CI 0·48 - 0·90 ) and similar in those on 150 mg dabigatran ( RR 1·01 ; 95 % CI 0·77 - 1·34 ) compared with those on warfarin . The effects of both doses of dabigatran compared with warfarin were not significantly different between patients with previous stroke or transient ischaemic attack and those without for any of the outcomes from RE-LY apart from vascular death ( 110 mg group compared with warfarin group , interaction p=0·038 ) . INTERPRETATION The effects of 110 mg dabigatran and 150 mg dabigatran twice daily in patients with previous stroke or transient ischaemic attack are consistent with those of other patients in RE-LY , for whom , compared with warfarin , 150 mg dabigatran  reduced stroke or systemic embolism and 110 mg dabligatran was non-inferior . [ corrected ] Most effects of both dabigatran doses were consistent in patients with versus those without previous stroke or transient ischaemic attack . FUNDING Boehringer Ingelheim BACKGROUND Patients with atrial fibrillation ( AF ) are at increased risk for ischemic stroke . In patients who have suffered a stroke , screening for AF is routinely performed only for a short period after the stroke as part of the evaluation for possible causes . If AF is detected after an ischemic stroke , oral anticoagulation therapy is recommended for secondary stroke prevention . In 25 % to 30 % of stroke patients , the stroke mechanism can not be determined ( cryptogenic stroke ) . The incidence of paroxysmal AF undetected by short-term monitoring in patients with cryptogenic stroke is unknown , but has important therapeutic implication s on patient care . The optimum monitoring duration and method of AF detection after stroke are unknown . The purpose of this study is to evaluate the incidence of AF and time to AF detection in patients with cryptogenic stroke using an insertable cardiac monitor . STUDY DESIGN The CRYSTAL AF trial is a r and omized prospect i ve study to evaluate a novel approach to long-term monitoring for AF detection in patients with cryptogenic stroke . Four hundred fifty cryptogenic stroke patients ( by definition , without a history of AF ) will be enrolled at approximately 50 sites in Europe , Canada , and the United States . Patients will be r and omized in a 1:1 fashion to st and ard arrhythmia monitoring ( control arm ) or implantation of the subcutaneous cardiac monitor ( Reveal XT ; Medtronic , Inc , Minneapolis , MN ) ( continuous monitoring arm ) . OUTCOMES The primary end point is time to detection of AF within 6 months after stroke . The clinical follow-up period will be at least 12 months . Study completion is expected at the end of 2012 INTRODUCTION Long-term cardiac monitoring with implantable loop recorders ( ILRs ) has revealed occult paroxysmal atrial fibrillation and flutter ( PAF ) in a substantial minority of cryptogenic ischemic stroke ( CIS ) patients . Herein , we aim to define the prevalence , clinical relevance , and risk factors for PAF detection following early poststroke ILR implantation . MATERIAL S AND METHODS A retrospective study of CIS patients ( n = 100 , mean age 65.8 years ; 52.5 % female ) who underwent ILR insertion during , or soon after , index stroke admission . Patients were prospect ively followed by the study cardiac electrophysiologist who confirmed the PAF diagnosis . Univariate and multivariate analyses compared clinical , laboratory , cardiac , and imaging variables between PAF patients and non-PAF patients . RESULTS PAF was detected in 31 of 100 ( 31 % ) CIS patients , and anticoagulation was initiated in almost all ( 30 of 31 , 96.8 % ) . Factors associated with PAF detection include older age ( mean [ year ] 72.9 versus 62.9 ; P = .003 ) , white race ( odds ratio [ OR ] , 4.5 ; confidence interval [ CI ] , 1.8 - 10.8 ; P = .001 ) , prolonged PR interval ( PR > 175 ms ; OR , 3.3 ; CI , 1.2 - 9.4 ; P = .022 ) , larger left atrial ( LA ) diameter ( mean [ cm ] 3.7 versus 3.5 ; P = .044 ) and LA volume index ( mean [ cc/m2 ] ; 30.6 versus 24.2 ; P = .014 ) , and lower hemoglobin (Hb)A1c ( mean [ % ] 6.0 versus 6.4 ; P = .036 ) . Controlling for age , obesity ( body mass index > 30 kg/m2 ; OR , 1.2 ; CI , 1.1 - 1.4 ; P = .033 ) was independently associated with PAF detection . DISCUSSION PAF was detected with high prevalence following early postcryptogenic stroke ILR implantation and result ed in significant management changes . Older age , increased PR interval , LA enlargement , and lower HbA1c are significantly associated with PAF detection . Controlling for age , obesity is an independent risk factor . A larger prospect i ve study is warranted to confirm these findings Aims Warfarin , a vitamin K antagonist ( VKA ) , has been the st and ard of care for stroke prevention in patients with atrial fibrillation ( AF ) .  Aspirin is recommended for low-risk patients and those unsuitable for warfarin . Apixaban is an oral anticoagulant that has demonstrated better efficacy than warfarin and aspirin in the ARISTOTLE and AVERROES studies , respectively , and causes less bleeding than warfarin . We evaluated the potential cost-effectiveness of apixaban against warfarin and aspirin from the perspective of the UK payer perspective . Results and methods A lifetime Markov model was developed to evaluate the pharmacoeconomic impact of apixaban compared with warfarin and aspirin in VKA suitable and VKA unsuitable patients , respectively . Clinical events considered in the model include ischaemic stroke , haemorrhagic stroke , intracranial haemorrhage , other major bleed , clinical ly relevant non-major bleed , myocardial infa rct ion , cardiovascular hospitalization and treatment discontinuations ; data from the ARISTOTLE and AVERROES trials and published mortality rates and event-related utility rates were used in the model . Apixaban was projected to increase life expectancy and quality -adjusted life years ( QALYs ) compared with warfarin and aspirin . These gains were expected to be achieved at a drug acquisition-related cost increase over lifetime . The estimated incremental cost-effectiveness ratio was £ 11 909 and £ 7196 per QALY gained with apixaban compared with warfarin and aspirin , respectively . Sensitivity analyses indicated that results were robust to a wide range of inputs . Conclusions Based on r and omized trial data , apixaban is a cost-effective alternative to warfarin and aspirin , in VKA suitable and VKA unsuitable patients with AF , respectively CONTEXT Warfarin has been shown to be highly efficacious for preventing  thromboembolism in atrial fibrillation in r and omized trials , but its effectiveness and safety in clinical practice is less clear . OBJECTIVE To evaluate the effect of warfarin on risk of thromboembolism , hemorrhage , and death in atrial fibrillation within a usual care setting . DESIGN Cohort study assembled between July 1 , 1996 , and December 31 , 1997 , and followed up through August 31 , 1999 . SETTING Large integrated health care system in Northern California . PATIENTS Of 13,559 adults with nonvalvular atrial fibrillation , 11,526 were studied , 43 % of whom were women , mean age 71 years , with no known contraindications to anticoagulation at baseline . MAIN OUTCOMES Ischemic stroke , peripheral embolism , hemorrhage , and death according to warfarin use and comorbidity status , as determined by automated data bases , review of medical records , and state mortality files . RESULTS Among 11,526 patients , 397 incident thromboembolic events ( 372 ischemic strokes , 25 peripheral embolism ) occurred during 25,341 person-years of follow-up , and warfarin therapy was associated with a 51 % ( 95 % confidence interval [ CI ] , 39%-60 % ) lower risk of thromboembolism compared with no warfarin therapy ( either no antithrombotic therapy or aspirin ) after adjusting for potential confounders and likelihood of receiving warfarin . Warfarin was effective in reducing thromboembolic risk in the presence or absence of risk factors for stroke . A nested case-control analysis estimated a 64 % reduction in odds of thromboembolism with warfarin compared with no antithrombotic therapy . Warfarin was also associated with a reduced risk of all-cause mortality ( adjusted hazard ratio , 0.69 ; 95 % CI , 0.61 - 0.77 ) . Intracranial hemorrhage was uncommon , but the rate was moderately higher among those taking vs those not taking warfarin ( 0.46 vs 0.23 per 100 person-years , respectively ; P = .003 , adjusted hazard ratio , 1.97 ; 95 % CI , 1.24 - 3.13 ) . However , warfarin therapy was not associated with an increased adjusted risk of nonintracranial major hemorrhage . The effects of warfarin were similar when patients with contraindications at baseline were analyzed separately or combined with those without contraindications ( total cohort of 13,559 ) . CONCLUSIONS Warfarin is very effective for preventing ischemic stroke in patients with atrial fibrillation in clinical practice while the absolute increase in the risk of intracranial hemorrhage is small . Results of r and omized trials of anticoagulation translate well into clinical care for patients with atrial fibrillation BACKGROUND For clinicians , confidence in atrial fibrillation ( AF ) episode classification is an important consideration when electing to use insertable cardiac monitors ( ICMs ) . OBJECTIVE The purpose of this study was to report on the improved AF detection algorithm in the Reveal LINQ ICM . METHODS The Reveal LINQ Usability Study is a nonr and omized , prospect i ve , multicenter trial . The ICM has been miniaturized , uses wireless telemetry for remote patient monitoring , and its AF algorithm includes a new p-wave filter . At 1 month post-device insertion , Holter monitor data were collected and annotated for true AF episodes ≥2 minutes , and performance metrics were evaluated by comparing Holter annotations with ICM detections . RESULTS The study enrolled 151 patients ( age 56.6 ± 12.1 , male 67 % ) . Reasons for monitoring included  AF ablation or AF management in 81.5 % ( n = 123 ) , syncope in 12.6 % ( n = 19 ) , and other indications in 5.9 % ( n = 9 ) of patients . Of the 138 patients with an analyzable Holter recording , a total of 112 true AF episodes were identified in 38 patients ( 27.5 % ) . The overall accuracy of the ICM to detect duration s of AF or non-AF episodes was 99.4 % , and the AF burden measured by the ICM was highly correlated with the Holter ( Pearson coefficient 0.995 ) . CONCLUSION The new AF detection algorithm in the Reveal LINQ ICM accurately detects the presence or absence of AF . Additionally , it showed high sensitivity in detecting AF duration in patients with a history of intermittent and symptomatic AF BACKGROUND Current guidelines recommend at least 24 hours of electrocardiographic ( ECG ) monitoring after an ischemic stroke to rule out atrial fibrillation . However , the most effective duration and type of monitoring have not been established , and the cause of ischemic stroke remains uncertain despite a complete diagnostic evaluation in 20 to 40 % of cases ( cryptogenic stroke ) . Detection of atrial fibrillation after cryptogenic stroke has therapeutic implication s. METHODS We conducted a r and omized , controlled study of 441 patients to assess whether long-term monitoring with an insertable cardiac monitor ( ICM ) is more effective than conventional follow-up ( control ) for detecting atrial fibrillation in patients with cryptogenic stroke . Patients 40 years of age or older with no evidence of atrial fibrillation during at least 24 hours of ECG monitoring  underwent r and omization within 90 days after the index event . The primary end point was the time to first detection of atrial fibrillation ( lasting > 30 seconds ) within 6 months . Among the secondary end points was the time to first detection of atrial fibrillation within 12 months . Data were analyzed according to the intention-to-treat principle . RESULTS By 6 months , atrial fibrillation had been detected in 8.9 % of patients in the ICM group ( 19 patients ) versus 1.4 % of patients in the control group ( 3 patients ) ( hazard ratio , 6.4 ; 95 % confidence interval [ CI ] , 1.9 to 21.7 ; P<0.001 ) . By 12 months , atrial fibrillation had been detected in 12.4 % of patients in the ICM group ( 29 patients ) versus 2.0 % of patients in the control group ( 4 patients ) ( hazard ratio , 7.3 ; 95 % CI , 2.6 to 20.8 ; P<0.001 ) . CONCLUSIONS ECG monitoring with an ICM was superior to conventional follow-up for detecting atrial fibrillation after cryptogenic stroke . ( Funded by Medtronic ; CRYSTAL AF Clinical Trials.gov number , NCT00924638 . ) BACKGROUND The BioMonitor 2 Pilot Study assessed the implantation procedure , the sensing amplitude and the remote monitoring transmission success rate of the second generation implantable cardiac monitor , the BioMonitor 2 ( Biotronik , Berlin , Germany ) . METHODS This was a prospect i ve , multi-centre , single-arm , non-r and omised study involving seven operators in five sites across Australia . Data were collected at implantation , during clinic visits at 1 week and 1 month post-implantation , and through wireless remote monitoring . RESULTS Thirty patients with indications for long-term cardiac monitoring underwent successful insertion of a study device . The median implantation time was 9 minutes ( interquartile range ( IQR ) 5 - 14 mins ) . The mean R-wave amplitude at 1 week was 0.75±0.39mV and remained stable over the follow-up period . Within 1 day , 97 % of the patients connected to the remote monitoring network and daily messages were transmitted on 93.8 % of all study days . Seventy-six per cent of patients transmitted at least one subcutaneous ECG ( sECG ) , with a median number of sECGs per patient of seven ( IQR 3 - 37 ) within 28 days . CONCLUSIONS The results of the BioMonitor 2 Pilot study confirm the excellent sensing amplitudes afforded by this new device and the utility of the implantation tools and technique . Patient compliance with and the transmission success rate of the home monitoring system were excellent OBJECTIVE Currently , there is no EQ-5D value set for Pol and . The primary objective of this study was to elicit EQ-5D Polish values using the time trade-off ( TTO ) method . METHODS Face-to-face interviews with visitors of in patients in eight medical centers in Warsaw , Skierniewice , and Puławy were carried out by trained interviewers . Quota sampling was used to achieve a representative sample of the Polish population with regard to age and sex . Modified protocol from the Measurement and Value of Health study was used . Each respondent ranked 10 health states and valued 4 health states using the visual analog scale and 23 using the TTO . Mean and variance stability tests were performed to determine whether using a larger number of health states per respondent would yield credible results . Modeling included r and om effects and r and om parameters models . RESULTS Between February and May 2008 , 321 interviews were performed . Modeling based on 6777 valuations result ed in an additive model with all coefficients statistically significant , R(2 ) equal to 0.45 , and value -0.523 for the worst possible health state . Means and variance did not differ significantly for states valued in the middle and at the end of the TTO exercise . CONCLUSIONS This is the first EQ-5D value set based on TTO in Central and Eastern Europe so far . Because the values differ considerably from those elicited in Western European countries , its use should be recommended for studies in Pol and . Increasing the number of health states that each respondent is asked to value using TTO seems feasible and justifiable AIMS To compare the quality of life ( QoL ) of those in atrial fibrillation ( AF ) aged 75 years and over with that of the general population , to explore what factors affect the QoL of those with AF , and to assess the sensitivity of the EuroQol ( EQ-5D ) and Short-Form 12 ( SF-12 ) generic health question naires in detecting differences in health status in those with AF in this age group . METHODS AND RESULTS The study population was 1762 men and women aged 75 years and over with confirmed AF who attended a r and omization clinic for the Birmingham Atrial Fibrillation Treatment of the Aged ( BAFTA ) study , a primary care based trial of stroke prevention . Patients self-completed the EQ-5D and SF-12 question naires , and a simple measure of disability ( Rankin ) . Cardiovascular co-morbidities were collected and number of drugs used as an additional proxy for co-morbidity . Quality -of-life outcomes were compared with general population sample s of the same age . On multiple regression , female gender , greater medication use , and disability were independently associated with lower QoL scores in AF . Those in AF with a Rankin score ≥2 had lower QoL scores , while those with a Rankin score < 2 had higher scores than the general population . Increasing co-morbidity was associated with reduced QoL scores , with the EQ-5D and SF-12 Physical Component Score showing similar sensitivity to these associations , and the SF-12 Mental Component Score showing less sensitivity . CONCLUSION In the absence of co-morbidity , chronic AF has little impact on generic QoL in an elderly non-acutely ill population INTRODUCTION Implantable loop recorders ( ILR ) are leadless subcutaneous devices that allow cardiac monitoring for up to 3 years and are a valuable tool in the diagnosis of arrhythmias , cryptogenic stroke and unexplained syncope . The Biotronik BioMonitor 2 is a novel , insertable ILR allowing long-term continuous monitoring with wireless telemetry options . METHODS A single-center , prospect i ve , observational study investigating the reliability of sensing quality and detection performance in the BioMonitor 2 ILR , as well as post-implantation patient satisfaction . R-wave amplitude was recorded immediately post implantation and 1 day post implantation , followed by extensive patient instruction . Follow-up was scheduled after 3 months , or after an event . Data from the ILR were retrieved , with documentation of all episodes , R-wave amplitude and noise burden . The anatomical position of the ILR was determined 1 day post implantation and after 3 months . A patient question naire was conducted after 3 months . RESULTS 30 consecutive patients ( mean age 71 ± 12 years , 56 % male ) were analyzed . Indications for ILR implantation were : unexplained syncope ( n = 24 , 80 % ) , suspected atrial fibrillation ( n = 4 , 13 % ) , cryptogenic stroke ( n = 1 , 3 % ) and palpitations ( n = 1 , 3 % ) . Median time from skin cut to suture was 8 min . No complications occurred . Mean R-wave amplitude at implantation was 0.84 ± 0.32 mV , at day 1 post implantation 0.96 ± 0.31 mV , and after a mean follow-up of 85 ± 24 days 1.02 ± 0.47 mV ( p = 0.01 ) . The mean noise burden was 1.4 ± 2 % . CONCLUSION Implantation of the novel BioMonitor 2 ILR is fast and uncomplicated . Initial sensing values are good and improve over time BACKGROUND The use of insertable cardiac monitors ( ICM ) has increased the rate of detection of atrial fibrillation ( AF ) among cryptogenic stroke ( CS ) patients . We describe a single-center experience for AF detection among CS patients receiving ICMs upon discharge after the index stroke event and attempt to identify predictors for AF detection . METHODS From April 2014 to October 2017 , patients receiving ICMs for CS who underwent > 60 days of monitoring were review ed . Chronic underlying medical illnesses , presence of left atrial enlargement ( LAE ) on echocardiography , and PR interval on admission electrocardiogram were assessed as predictors of AF detection . RESULTS A total of 234 patients ( median age 72 [ 61 , 78 ] years , 45 % women ) met inclusion criteria and were followed for a median of 536 [ 282 , 848 ] days . Among studied patients , 68 patients ( 29 % ) were found to have AF at a median of 94.5 [ 16 , 239 ] days from ICM placement . CS patients with AF were significantly older ( p < 0.001 ) , and there was a significantly higher proportion of women ( p = 0.003 ) when compared to CS patients without AF . Neither presence of LAE nor prolonged PR interval was predictive of AF detection . CONCLUSION Almost one-third of CS patients monitored with an ICM were found to have previously undiagnosed AF . CS patients found to have AF were older and more commonly women . Prospect i ve studies are needed to better identify predictors for early AF among the broader population of all CS patients Recently , the clinical entity embolic stroke of undetermined source ( ESUS ) has been defined for patients with ischemic strokes , where neither a cardioembolic nor a non-cardiac source can be detected . These patients may suffer from asymptomatic atrial fibrillation ( AF ) , terminating spontaneously and thus eluding detection . Implantable loop recorders ( ILR ) with automatic AF detection algorithms can detect short-lasting , sub clinical AF . The aim of this study was to prospect ively assess and predict AF detection in patients with ESUS using ILR with daily remote interrogation . Patients with acute ESUS received an ILR , were seen every 6 months and additionally interrogated their ILR daily using remote monitoring . The incidence of AF detection was assessed and parameters which might predict AF detection ( clinical and from magnetic resonance tomography ) were analysed . ILR implantation was performed in 123 patients on average 20 days after stroke . During a mean follow-up of 12.7±5.5 months , AF was documented and manually confirmed in 29 of 123 patients ( 23.6 % ) . First AF detection occurred on average after 3.6±3.4 months of monitoring . Patients with AF were on average older , had a higher CHA2DS2-VASc score and more often cerebral microangiopathy . In conclusion , AF can be documented in approximately 25 % of patients with the diagnosis of ESUS after careful work-up within a year of monitoring by an ILR and daily remote interrogation . This had important therapeutic consequences ( initiation of anticoagulation for secondary stroke prevention ) in these patients
target: When each device is compared incrementally , BioMonitor 2-AF dominates Reveal LINQ and Confirm RX .
background: BACKGROUND Cryptogenic stroke is a stroke for which no cause is identified after st and ard diagnostic tests .
  Long-term implantable cardiac monitors may be better at diagnosing atrial fibrillation and provide an opportunity to reduce the risk of stroke recurrence with anticoagulants .
  OBJECTIVES The objectives were to assess the diagnostic test accuracy , clinical effectiveness and cost-effectiveness of three implantable monitors [ BioMonitor 2-AF ™ ( Biotronik SE & Co. KG , Berlin , Germany ) , Confirm Rx ™ ( Abbott Laboratories , Lake Bluff , IL , USA ) and Reveal LINQ ™ ( Medtronic plc , Minneapolis , MN , USA ) ] in patients who have had a cryptogenic stroke and for whom no atrial fibrillation is detected after 24 hours of external electrocardiographic monitoring .