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Background: Phenotypic classification is a method of grouping patients with similar phenotypes., Aim: We aimed to use phenotype classification based on a clustering process for risk stratification of patients with non-valvular atrial fibrillation (AF) and second, to assess the benefit of the Atrial Fibrillation Better Care (ABC) pathway., Methods: Patients with AF were prospectively enrolled from 27 hospitals in Thailand from 2014 to 2017, and followed up every 6 months for 3 years. Cluster analysis was performed from 46 variables using the hierarchical clustering using the Ward minimum variance method. Outcomes were a composite of all-cause death, ischemic stroke/systemic embolism, acute myocardial infarction and heart failure., Results: A total of 3405 patients were enrolled (mean age 67.8 ± 11.3 years, 58.2% male). During the mean follow-up of 31.8 ± 8.7 months. Three clusters were identified: Cluster 1 had the highest risk followed by Cluster 3 and Cluster 2 with a hazard ratio (HR) and 95% confidence interval (CI) of composite outcomes of 2.78 (2.25, 3.43), P < 0.001 for Cluster 1 and 1.99 (1.63, 2.42), P < 0.001 for Cluster 3 compared with Cluster 2. Management according to the ABC pathway was associated with reductions in adverse clinical outcomes especially those who belonged to Clusters 1 and 3 with HR and 95%CI of the composite outcome of 0.54 (0.40, 073), P < 0.001 for Cluster 1 and 0.49 (0.38, 0.63), P < 0.001 for Cluster 3., Conclusion: Phenotypic classification helps in risk stratification and prognostication. Compliance with the ABC pathway was associated with improved clinical outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: We evaluated the impact of early rhythm control (ERC) on diabetes-related complications and mortality in subjects with type 2 diabetes mellitus (T2DM) and atrial fibrillation (AF)., Methods: This observational cohort study based on the Korean National Health Insurance Service claims database from 2009 to 2016, divided newly diagnosed AF patients with T2DM into ERC or usual care groups based on receiving rhythm control treatment within 1 year of AF diagnosis. The primary outcome was ischemic stroke, and the secondary outcomes were macro/microvascular complications, and all-cause death., Results: Among 47,509 subjects (mean age 66.7 ± 10.5 years; 61.8 % men; mean CHA 2 DS 2 -VASc score 4.6 ± 1.8; mean follow-up 4.3 ± 2.3 years; mean DM duration 5.6 ± 4.7 years), 23.1 % received ERC, and 76.9 % did not (usual care group). ERC was associated with lower risks of ischemic stroke, macrovascular and microvascular complications, and all-cause death compared to usual care (adjusted hazard ratios [95 % confidence interval]: 0.77 [0.70-0.85], 0.79 [0.73-0.86], 0.86 [0.82-0.90], and 0.92 [0.87-0.98], p < 0.001, <0.001, <0.001, and 0.012, respectively)., Conclusions: Early rhythm control was associated with reduced risks of diabetes-related complications and mortality in subjects with T2DM and AF. Rhythm control within 1 year of AF diagnosis with proper anticoagulation should be considered to prevent adverse outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

To investigate the time-dependent effects of traditional risk factors on functional disability in all-cause mortality post-stroke, we evaluated data from a long-term stroke cohort. Baseline cerebrovascular risk factors (CVRF) and functionality at 1 and 6 months were evaluated in survivors from a prospective stroke cohort using the modified Rankin scale (m-RS), which classifies participants as improvement of disability, unchanged disability (at least moderate), and worsening disability. Cox regression models considering baseline risk factors, medication use, and functionality 6 months after stroke were fitted to identify their time-dependent effects up to 12 years of follow-up. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) are presented. Among 632 survivors (median age 68, 54% male, 71% first-ever episode), age and functional disability (unchanged and worsening) 6 months after ischemic stroke had time-dependent effects on all-cause mortality risk up to 12 years of follow-up. The most impacting risk factors were unchanged (at least moderate) (HR, 2.99; 95%CI: 1.98-4.52) and worsening disability (HR, 2.85; 95%CI: 1.26-6.44), particularly in the first two years after a stroke event (Time 1: ≥6 mo to <2.5 y). Worsening disability also impacted mortality in the period from ≥2.5 to <7.5 years (Time 2) of follow-up (HR, 2.43 (95%CI: 1.03-5.73). Other baseline factors had a fixed high-risk effect on mortality during follow-up. Post-stroke and continuous medication use had a fixed protective effect on mortality. Functional disability was the main contributor with differential risks of mortality up to 12 years of follow-up.

Background: Patients with atrial fibrillation are characterized by great clinical heterogeneity and complexity. The usual classifications may not adequately characterize this population. Data-driven cluster analysis reveals different possible patient classifications., Aims: To identify different clusters of patients with atrial fibrillation who share similar clinical phenotypes, and to evaluate the association between identified clusters and clinical outcomes, using cluster analysis., Methods: An agglomerative hierarchical cluster analysis was performed in non-anticoagulated patients from the Loire Valley Atrial Fibrillation cohort. Associations between clusters and a composite outcome comprising stroke/systemic embolism/death and all-cause death, stroke and major bleeding were evaluated using Cox regression analyses., Results: The study included 3434 non-anticoagulated patients with atrial fibrillation (mean age 70.3±17 years; 42.8% female). Three clusters were identified: cluster 1 was composed of younger patients, with a low prevalence of co-morbidities; cluster 2 included old patients with permanent atrial fibrillation, cardiac pathologies and a high burden of cardiovascular co-morbidities; cluster 3 identified old female patients with a high burden of cardiovascular co-morbidities. Compared with cluster 1, clusters 2 and 3 were independently associated with an increased risk of the composite outcome (hazard ratio 2.85, 95% confidence interval 1.32-6.16 and hazard ratio 1.52, 95% confidence interval 1.09-2.11, respectively) and all-cause death (hazard ratio 3.54, 95% confidence interval 1.49-8.43 and hazard ratio 1.88, 95% confidence interval 1.26-2.79, respectively). Cluster 3 was independently associated with an increased risk of major bleeding (hazard ratio 1.72, 95% confidence interval 1.06-2.78)., Conclusion: Cluster analysis identified three statistically driven groups of patients with atrial fibrillation, with distinct phenotype characteristics and associated with different risks for major clinical adverse events., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction: Atrial fibrillation (AF) is a common arrhythmia associated with 30% of strokes, as well as other cardiovascular disease, dementia and death. AF meets many criteria for screening, but there is limited evidence that AF screening reduces stroke. Consequently, no countries recommend national screening programmes for AF. The Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) trial aims to determine whether screening for AF is effective at reducing risk of stroke. The aim of the pilot study is to assess feasibility of the main trial and inform implementation of screening and trial procedures., Methods and Analysis: SAFER is planned to be a pragmatic randomised controlled trial (RCT) of over 100 000 participants aged 70 years and over, not on long-term anticoagulation therapy at baseline, with an average follow-up of 5 years. Participants are asked to record four traces every day for 3 weeks on a hand-held single-lead ECG device. Cardiologists remotely confirm episodes of AF identified by the device algorithm, and general practitioners follow-up with anticoagulation as appropriate. The pilot study is a cluster RCT in 36 UK general practices, randomised 2:1 control to intervention, recruiting approximately 12 600 participants. Pilot study outcomes include AF detection rate, anticoagulation uptake and other parameters to incorporate into sample size calculations for the main trial. Questionnaires sent to a sample of participants will assess impact of screening on psychological health. Process evaluation and qualitative studies will underpin implementation of screening during the main trial. An economic evaluation using the pilot data will confirm whether it is plausible that screening might be cost-effective., Ethics and Dissemination: The London-Central Research Ethics Committee (19/LO/1597) and Confidentiality Advisory Group (19/CAG/0226) provided ethical approval. Dissemination will be via publications, patient-friendly summaries, reports and engagement with the UK National Screening Committee., Trial Registration Number: ISRCTN72104369., Competing Interests: Competing interests: JM has performed consultancy work for BMS/Pfizer and Omron. FDRH reports occasional consultancy for BMS/Pfizer, Bayer and BI over the past 5 years. NA is a member of the UK National Screening Committee’s Adult Reference Group. MS is a full-time employee of AstraZeneca. MRC reports consultancy for AstraZeneca, Abbott, Medtronic, Bayer, Novartis, Boehringer-Ingelheim-Lilly Alliance, Servier & Pfizer over the past 5 years. RMc’s employer the University of Oxford receives consultancy and licencing payments from Omron and Sensyne for BP telemonitoring interventions. GYHL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. No fees are received personally. SJG has received honoraria from Astra Zeneca for lectures at postgraduate educational meetings for primary care teams about type 2 diabetes. BF has received speaker fees, honoraria, and non-financial support from the BMS and Pfizer Alliance; grants to the Institution for investigator-initiated studies from the BMS and Pfizer Alliance; and loan devices for investigatorinitiated studies from Alivecor: all were unrelated to the present study but related to screening for AF., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Patient frailty amongst patients with nonvalvular atrial fibrillation (NVAF) is associated with adverse health outcomes and increased risk of mortality. Additional evidence is needed to evaluate effective and safe NVAF treatment in this patient population., Objectives: This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) amongst frail NVAF patients prescribed nonvitamin K antagonist oral anticoagulants (NOACs) or warfarin., Methods: This comparative retrospective observational study of frail, older NVAF patients who initiated apixaban, dabigatran, rivaroxaban or warfarin from 01JAN2013-30SEP2015 was conducted using Medicare and 3 US commercial claims databases. To compare each drug, 6 propensity score-matched (PSM) cohorts were created. Patient cohorts were pooled from 4 databases after PSM. Cox models were used to estimate hazard ratios (HR) of S/SE and MB., Results: Amongst NVAF patients, 34% (N = 150 487) met frailty criteria. Apixaban and rivaroxaban were associated with a lower risk of S/SE vs warfarin (apixaban: HR: 0.61, 95% CI: 0.55-0.69; rivaroxaban: HR: 0.79, 95% CI: 0.72-0.87). For MB, apixaban (HR: 0.62, 95% CI: 0.57-0.66) and dabigatran (HR: 0.79, 95% CI: 0.70-0.89) were associated with a lower risk and rivaroxaban (HR: 1.14, 95% CI: 1.08-1.21) was associated with a higher risk vs warfarin., Conclusion: Amongst this cohort of frail NVAF patients, NOACs were associated with varying rates of stroke/SE and MB compared with warfarin. Due to the lack of real-world data regarding OAC treatment in frail patients, these results may inform clinical practice in the treatment of this patient population., (© 2020 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Comparative data of non-vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF)., Objective: We compared effectiveness and safety of standard and reduced dose NOAC in AF patients., Methods: Using Danish nationwide registries, we included all oral anticoagulant-naïve AF patients who initiated NOAC treatment (2012-2016). Outcome-specific and mortality-specific multiple Cox regressions were combined to compute average treatment effects as 1-year standardized differences in stroke and bleeding risks (g-formula)., Results: Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran-reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% and 2.51-2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1-year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42-3.17%); corresponding absolute risk differences (95% CI) were for dabigatran -0.93% (-1.45% to -0.38%) and apixaban, -0.54% (-0.99% to -0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1-year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22-0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06-0.41%) and apixaban, 0.18% (0.01-0.34%)., Conclusions: Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban., (© 2017 The Association for the Publication of the Journal of Internal Medicine.)

Concepts and our approaches to stroke prevention in atrial fibrillation (AF) have changed markedly over the last decade. There has been an evolution over the approach to stroke and bleeding risk assessment, as well as new treatment options. An increasing awareness of AF has led to calls to improve the detection of and population screening for AF. Stroke and bleeding risk assessment continues to evolve, and the ongoing debate on balance between simplicity and practicality, against precision medicine will continue. In this review article, we provide an overview of past, present and the (likely) future concepts and approaches to stroke prevention in AF. We propose three simple steps (the Birmingham '3-step') that offers a practical management pathway to help streamline and simplify decision-making for stroke prevention in patients with AF.

Oral anticoagulation therapy has reduced the risk of ischaemic stroke and improved the outcomes for patients with atrial fibrillation considerably. The emergence of the non-vitamin K oral anticoagulants as alternatives to vitamin K antagonists has significantly changed the practice of stroke prevention in atrial fibrillation. As the main complication with antithrombotic therapy is bleeding, physicians should always balance the risk of ischaemic stroke against intracranial haemorrhage and intervene where appropriate to reduce both risks. Individual approach is often mandatory due to heterogeneity of the risks and patient preferences. The purpose of this review is to summarise the current knowledge of the oral anticoagulation therapy in atrial fibrillation patients and guide physicians with the management of anticoagulants based on data from clinical trials and systematic reviews.

Retinal vascular events are perceived to be related to various cardiovascular complications. We conducted a systematic review to assess the relationship between retinal artery/vein occlusions (RAO/RVO) and the incidence of mortality, stroke, and myocardial infarction (MI). A comprehensive electronic literature search selected 93 relevant studies between 1992-2015: 16 articles qualified for inclusion (7 for mortality rate and MI, 11 for stroke). No published articles examined associations of RAO to mortality or MI, but only to stroke. Because of the heterogeneity of studies, no meta-analysis was performed. The association with mortality risk was highest at ~34.7% in RVO subgroup; whereas for MI, the risk was comparatively lower at 3.9-5.7% for RVO. There was no significant difference in stroke rate when comparing central and branch RVO subgroups (6.5%), but was significantly higher at 19.6-25% in RAO. There is a positive association of retinal vascular events to mortality, stroke, and MI. RAO is associated with a higher risk of stroke. Given that RAO and RVO patients would generally present to ophthalmologists, their high cardiovascular risk should include a referral for cardiovascular assessment as part of their management protocol.

A recording of = 30 seconds is required to diagnose paroxysmal atrial fibrillation when using ambulatory ECG monitoring. It is unclear if shorter runs are relevant with regards to stroke risk. Methods An online survey of cardiologists and stroke physicians was carried out to assess current management of patients with short runs of atrial arrhythmia within Europe. Results Respondents included 311 clinicians from 32 countries. To diagnose atrial fibrillation, 80% accepted a single 12-lead ECG and 36% accepted a single run of > 30 seconds on ambulatory monitoring. Stroke physicians were twice as likely to accept < 30 seconds of arrhythmia as being diagnostic of atrial fibrillation (OR 2.43, 95% CI 1.19-4.98). They were also more likely to advocate anticoagulation for hypothetical patients with lower risk; OR 1.9 (95% CI 1.0-3.5) for a patient with CHA2DS2-VASc = 2. Conclusion Short runs of atrial fibrillation create a dilemma for physicians across Europe. Stroke physicians and cardiologists differ in their diagnosis and management of these patients.

The main priority in atrial fibrillation (AF) management is stroke prevention, following which decisions about rate or rhythm control are focused on the patient, being primarily for management of symptoms. Given that AF is commonly associated with various comorbidities, risk factors such as hypertension, heart failure, diabetes mellitus and sleep apnoea should be actively looked for and managed in a holistic approach to AF management. The objective of this review is to provide an overview of modern AF stroke prevention with a focus on tailored treatment strategies. Biomarkers and genetic factors have been proposed to help identify 'high-risk' patients to be targeted for oral anticoagulation, but ultimately their use must be balanced against that of more simple and practical considerations for everyday use. Current guidelines have directed focus on initial identification of 'truly low-risk' patients with AF, that is those patients with a CHA2 DS2 -VASc [congestive heart failure, hypertension, age ≥75 years (two points), diabetes mellitus, stroke (two points), vascular disease, age 65-74 years, sex category] score of 0 (male) or 1 (female), who do not need any antithrombotic therapy. Subsequently, patients with ≥1 stroke risk factors can be offered effective stroke prevention, that is oral anticoagulation. The SAMe-TT2 R2 [sex female, age <60 years, medical history (>2 comorbidities), treatment (interacting drugs), tobacco use (two points), race non-Caucasian (two points)] score can help physicians make informed decisions on those patients likely to do well on warfarin (SAMe-TT2 R2 score 0-2) or those who are likely to have a poor time in therapeutic range (SAMe-TT2 R2 score >2). A clinically focused tailored approach to assessment and stroke prevention in AF with the use of the CHA2 DS2 VASc, HAS-BLED [hypertension, abnormal renal/liver function (one or two points), stroke, bleeding history or predisposition, labile international normalized ratio, elderly (>65 years) drugs/alcohol concomitantly (one or two points)] and SAMeTT2 R2 scores to evaluate stroke risk, bleeding risk and likelihood of successful warfarin therapy, respectively, is discussed., (© 2016 The Association for the Publication of the Journal of Internal Medicine.)

Background and Rationale: The increasing use of oral anticoagulants, mostly to prevent ischemic stroke due to atrial fibrillation in an ageing population, has been associated with a fivefold increased incidence of oral anticoagulant-associated intracerebral hemorrhage: a rare, serious, and unpredictable complication. We hypothesize that cerebral microbleeds and other markers of cerebral small vessel disease on magnetic resonance imaging, and genetic polymorphisms (e.g. influencing cerebral small vessel integrity or anticoagulation stability), are associated with an increased risk of oral anticoagulant-associated intracerebral hemorrhage, with potential to improve risk prediction., Aims: (1) To determine the incidence, clinical, radiological, and genetic associations of oral anticoagulant-associated intracerebral hemorrhage in a prospective, multicentre cohort study of patients with atrial fibrillation-related ischemic stroke or transient ischemic attack started on oral anticoagulants; (2) To investigate characteristics of oral anticoagulant-associated intracerebral hemorrhage compared with non-oral anticoagulants related intracerebral hemorrhage in a prospective study., Design and Methods: Study 1: Prospective, multicentre, inception cohort study of 1425 adults started on oral anticoagulants (including vitamin K antagonists and the nonvitamin K oral anticoagulants) after recent ischemic stroke and concurrent atrial fibrillation. Participants will have standardized brain magnetic resonance imaging (including a T2*-weighted gradient-recalled echo sequence) and DNA sample collection at baseline, with two-year follow-up by postal questionnaire and medical records surveillance for symptomatic intracranial hemorrhage, other serious vascular events, and death. We will compare the rates of symptomatic intracranial hemorrhage (primary outcome; subclassified as intracerebral, subdural, extradural, intraventricular), other vascular events, and death (secondary outcomes) in participants with one or more cerebral microbleeds to the rates in those without cerebral microbleeds., Study: Prospective case-control study of oral anticoagulant-associated intracerebral hemorrhage compared with non-oral anticoagulant-associated intracerebral hemorrhage to investigate genetic, clinical, and radiological associations with oral anticoagulant-associated intracerebral hemorrhage. In participants with intracerebral hemorrhage (including at least 300 with oral anticoagulant-associated intracerebral hemorrhage), we will collect a DNA sample, standardized clinical data and routine brain imaging (magnetic resonance imaging or computed tomography), and information on functional outcome., Expected Outcomes: We will identify the factors associated with increased intracranial hemorrhage risk after oral anticoagulants for secondary prevention after ischemic stroke due to atrial fibrillation. We will determine clinical, radiological and genetic factors, and clinical outcomes associated with oral anticoagulant-associated intracerebral hemorrhage., (© 2015 World Stroke Organization.)

Background: Women represent a large proportion of patients with atrial fibrillation (AF) and tend to have higher risk of stroke., Aims: This study examines gender differences in the utilisation of oral anticoagulation (OAC) and prognosis (i.e. stroke and death) in AF patients in UK general practice., Design: Retrospective observational study., Methods: The Guidance on Risk Assessment and Stroke Prevention in Atrial Fibrillation (GRASP-AF) tool was employed to identify AF patients from 11 general practices in Darlington, England., Results: Two thousand two hundred and fifty-nine AF patients (mean±SD age 76 ± 12 years; 46% female) were identified. Based on CHA2 DS2 -VASc score 95% of women and 90% of men were at moderate-high risk of stroke. Women with moderate-high risk of stroke were treated with OAC less frequently than men (47% vs. 52%, p = 0.006). Overall rates of stroke and all-cause mortality were higher among women than men (p = 0.02 and p < 0.001). However, there was no significant gender difference in these outcomes in patients receiving OAC (p = 0.52 for stroke, p = 0.18 for death). Among people not receiving OAC where indicated, female gender was associated with an increased risk of stroke before (p = 0.01), and after (p = 0.04), adjustment for stroke risk factors. Women not receiving OAC had a higher risk of death on univariate regression analysis (p = 0.002), but not after adjustment for stroke risk factors (p = 0.53)., Conclusion: Women with AF are at higher risk of stroke than men without OAC. The gender-related differences in risk of stroke disappear if OAC is used. Despite this, women are more likely not to receive OAC., (© 2015 John Wiley & Sons Ltd.)

Background: Darexaban (YM150) is a novel oral anticoagulant that directly inhibits factor Xa., Objectives: To investigate the optimal daily dose regimen of YM150 in subjects with non-valvular atrial fibrillation (NVAF)., Methods: In this multicenter, double-blind, double-dummy, randomized, parallel-group, dose-confirmation study (NCT00938730), patients with NVAF were randomized to darexaban 15 mg bid, 30 mg qd, 30 mg bid, 60 mg qd, 60 mg bid or 120 mg qd, or warfarin qd. The primary endpoint was the incidence of adjudicated major and/or clinically relevant non-major bleeding events. Secondary endpoints included efficacy, pharmacodynamics, safety and tolerability., Results: A total of 1297 patients were randomized and finally included in the trial (median age, 66 [range 30-89] years; 68.8% male): 981 completed treatment for a median of 28 weeks (interquartile range, 24-36). At daily doses of 30-60 mg, darexaban bid resulted in fewer bleeding events than darexaban qd. For darexaban 120 mg, the bid regimen produced more bleeding events than the qd regimen. Although few efficacy endpoints occurred, these decreased with increasing daily darexaban dose. Darexaban decreased plasma D-dimer levels (index of thrombogenesis) after 4 weeks of treatment by 21.5-33.8% compared with baseline, which was comparable with warfarin at the higher darexaban doses. Darexaban was well tolerated with no liver toxicity., Conclusions: In this Phase II study in patients with NVAF, a lower bleeding rate was observed in the 120 mg daily darexaban group compared with warfarin with a reduction in plasma D-dimer as marker for hemostasis. Further investigation of the optimal dose of darexaban for the prevention of stroke in patients with NVAF would need to be considered., (© 2015 International Society on Thrombosis and Haemostasis.)

As non-valvular atrial fibrillation (AF) brings a risk of stroke, oral anticoagulants (OAC) are recommended. In 'real world' clinical practice, many patients (who may be, or perceived to be, intolerant of OACs) are either untreated or are treated with anti-platelet agents. We hypothesised that edoxaban has a better net clinical benefit (NCB, balancing the reduction in stroke risk vs increased risk of haemorrhage) than no treatment or anti-platelet agents. We performed a network meta-analysis of published data from 24 studies of 203,394 AF patients to indirectly compare edoxaban with aspirin alone, aspirin plus clopidogrel, and placebo. Edoxaban 30 mg once daily significantly reduced the risk of all stroke, ischaemic stroke and mortality compared to placebo and aspirin. Compared to aspirin plus clopidogrel, there was a lower risk of intra-cranial haemorrhage (ICH). Edoxaban 60 mg once-daily had a reduced risk of any stroke and systemic embolism compared to placebo, aspirin, and aspirin plus clopidogrel. Mortality rates for both edoxaban doses were estimated to be lower compared to any anti-platelet, and significantly lower compared to placebo. With overall reduced risk of ischemic stroke and ICH, both edoxaban doses bring a NCB of mean (SD) 1.68 (0.15) saved events per 100 patients per year compared to anti-platelet drugs in a clinical trial population. The NCB was demonstrated to be lower, at 0.77 (0.12) events saved (p< 0.01) when modeled to data from a 'real world' cohort of AF patients. In conclusion, edoxaban is likely to provide even better protection from stroke and ICH than placebo, aspirin alone, or aspirin plus clopidogrel in both clinical trial populations and unselected community populations. Both edoxaban doses would also bring a positive NCB compared to anti-platelet drugs or placebo/non-treatment based on 'real world' data.

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and is a growing health problem that is associated with a significantly increased risk of stroke and thromboembolism. Oral anticoagulant (OAC) therapy reduces the risk of stroke and all-cause mortality in patients with AF. OAC therapy is commonly given as a well-controlled vitamin K antagonist (VKA; e.g. warfarin) and can reduce the risk of stroke in AF patients by almost two-thirds. However, the widespread use of VKAs has been hampered by the unpredictable pharmacokinetic and pharmacodynamic properties of the drugs and justifiable concerns about the consequent risk of haemorrhage. The non-VKA OACs (NOACs) have revolutionized thromboprophylaxis in AF by providing therapeutic options with predictable pharmacodynamic and pharmacokinetic properties that are as efficacious as warfarin in the prevention of stroke and thromboembolism but are more convenient to use. In this review, we provide a patient-centred framework to assist clinicians in recommending the right OAC therapy to fit the individual patient with AF, including methods for stratifying the risk of stroke and haemorrhage and the chances of achieving tight control of VKA anticoagulation, and we discuss the properties of the NOACs that favour their use in particular patient cohorts., (© 2015 The Association for the Publication of the Journal of Internal Medicine.)

Background: There is a perception among physicians that lack of routine monitoring with non-vitamin K antagonist oral anticoagulants (NOACs) may lead to poor adherence to medication. We studied adherence during the first year of usage in a cohort of patients with newly diagnosed non-valvular atrial fibrillation (AF) started on the NOAC, dabigatran etexilate., Methods and Results: Nationwide Danish patient and prescription purchase registries were used to identify newly diagnosed AF patients taking dabigatran, comorbidities, and refill patterns under a twice-daily, one pill regimen. Adherence was characterized among remaining users (N = 2960) after 1 year using the proportion of days covered (PDC), gap rates and restart rates. The overall 1-year PDC was 83.9%, with 76.8% of patients having a 1-year PDC in excess of 80%. Patients with a CHA2 DS2 -VASc score ≥ 2 were more adherent to medication regimes than patients with a CHA2 DS2 -VASc score of 1 (PDC ratio, 1.12; 95% confidence interval [CI], 1.08-1.17) and generally patients with higher morbidity showed more adherence. Patients with prior bleeding were not less adherent to medication regimes than patients with no prior bleeding (PDC ratio, 1.02; 95% CI, 0.98-1.06). The overall gap rate was 1.4 gaps per year. There were no clear tendencies in gap rates among subgroups, although patients with higher morbidity tended to have slightly more, but shorter, gap periods., Conclusions: More than 75% of patients were showed > 80% adherence to medication regimes during the first year. Patients with higher morbidity, including patients with a higher risk of stroke or bleeding, exhibited better adherence. This improvement may be attributable to more regular contact with the healthcare system., (© 2015 International Society on Thrombosis and Haemostasis.)

Background: The prognostic significance of age and continuous positive airway pressure (CPAP) therapy on cardiovascular disease in patients with sleep apnoea has not been assessed previously., Methods: Using nationwide databases, the entire Danish population was followed from 2000 until 2011. First-time sleep apnoea diagnoses and use of CPAP therapy were determined. Incidence rate ratios (IRRs) of ischaemic stroke and myocardial infarction (MI) were analysed using Poisson regression models., Results: Amongst 4.5 million individuals included in the study, 33 274 developed sleep apnoea (mean age 53, 79% men) of whom 44% received persistent CPAP therapy. Median time to initiation of CPAP therapy was 88 days (interquartile range 34-346). Patients with sleep apnoea had more comorbidities compared to the general population. Crude rates of MI and ischaemic stroke were increased for sleep apnoea patients (5.4 and 3.6 events per 1000 person-years compared to 4.0 and 3.0 in the general population, respectively). Relative to the general population, risk of MI [IRR 1.71, 95% confidence interval (CI) 1.57-1.86] and ischaemic stroke (IRR 1.50, 95% CI 1.35-1.66) was significantly increased in patients with sleep apnoea, in particular in patients younger than 50 years (IRR 2.12, 95% CI 1.64-2.74 and IRR 2.34, 95% CI 1.77-3.10, respectively). Subsequent CPAP therapy was not associated with altered prognosis., Conclusions: Sleep apnoea is associated with increased risk of ischaemic stroke and MI, particularly in patients younger than 50 years of age. CPAP therapy was not associated with a reduced rate of stroke or MI., (© 2014 The Association for the Publication of the Journal of Internal Medicine.)

Background: Atrial fibrillation (AF) increases the risk of stroke, but this risk is not homogenous. Many risk factors contribute to stroke risk however, the evidence for female sex as a risk factor is less well-established., Aim: To perform a systematic review and meta-analysis of the available evidence to establish if female sex is a risk factor for stroke/thromboembolism among patients with AF., Methods: A systematic literature search was conducted using Medline. The search term 'atrial fibrillation' was used in combination with 'stroke risk', 'thromboembolism', 'female' and 'gender differences' and returned 735 articles, of which 17 were appraised and included. Females with AF were compared with males with AF for the outcome of stroke/thromboembolism., Results: Seventeen studies, 5 randomized-controlled trials and 12 prospective observational studies were included; 10 demonstrated an increased risk of stroke in women. Meta-analysis of the 17 studies revealed a 1.31-fold (95% confidence intervals (CIs) 1.18-1.46) elevated risk of stroke in women with AF; the risk appearing greatest for women aged ≥75 years. Only three studies compared entirely anticoagulated populations; stroke rates among these patients varied from 1.2-1.44% per-patient year for men and 2.08-2.43% per-patient year for women. Risk of stroke in women appeared similar regardless of oral anticoagulation therapy [risk ratio (95% CI 1.29 (1.09-1.52) and 1.49 (1.17-1.90) in non-anticogulated vs. anticoagulated/mixed cohorts, respectively)., Conclusions: Women with AF are at increased risk of stroke, particularly elderly women. Comprehensive stroke risk assessment, including sex as a risk factor, should be undertaken in all AF patients., (© The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Several validated risk stratification schemes for prediction of ischaemic stroke (IS)/thromboembolism (TE) and major bleeding are available for patients with non-valvular atrial fibrillation (NVAF). On the basis for multiple common risk factors for IS/TE and bleeding, it has been suggested that composite risk prediction scores may be more practical and user-friendly than separate scores for bleeding and IS/TE. In a long-term prospective hospital registry of anticoagulated patients with newly diagnosed AF, we compared the predictive value of existing risk prediction scores as well as composite risk scores, and also compared these risk scoring systems using composite endpoints. Endpoint 1 was the simple composite of IS and major bleeds. Endpoint 2 was based on a composite of IS plus intracerebral haemorrhage (ICH). Endpoint 3 was based on weighted coefficients for IS/TE and ICH. Endpoint 4 was a composite of stroke, cardiovascular death, TE and major bleeding. The incremental predictive value of these scores over CHADS2 (as reference) for composite endpoints was assessed using c-statistic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Of 8,962 eligible individuals, 3,607 (40.2%) had NVAF and were on OAC at baseline. There were no statistically significant differences between the c-statistics of the various risk scores, compared with the CHADS2 score, regardless of the endpoint. For the various risk scores and various endpoints, NRI and IDI did not show significant improvement (≥1%), compared with the CHADS2 score. In conclusion, composite risk scores did not significantly improve risk prediction of endpoints in patients with NVAF, regardless of how endpoints were defined. This would support individualised prediction of IS/TE and bleeding separately using different separate risk prediction tools, and not the use of composite scores or endpoints for everyday 'real world' clinical practice, to guide decisions on thromboprophylaxis.

Background: Retinal vascular occlusions may constitute an independent risk factor for stroke in patients with atrial fibrillation., Methods: We performed a retrospective study on a nationwide cohort with atrial fibrillation from 1997 to 2008. The rate of stroke/systemic thromboembolism (TE)/transitory ischemic attack (TIA) was determined for atrial fibrillation patients with and without a history of retinal vascular occlusion. A Cox regression analysis, adjusted for risk factors and medications, was performed to determine the independent predictive value of retinal arterial or venous occlusion for the risk of ischemic stroke, TE or TIA in atrial fibrillation patients., Results: We included 87 202 patients with non-valvular atrial fibrillation. At baseline, a history of retinal arterial occlusion was diagnosed in 224 patients (0.26%) and a history of retinal venous occlusion in 361 (0.41%). Patients without retinal occlusion had a rate of stroke/TE/TIA of 4.52 (95% confidence interval [CI] 4.44-4.60). For patients with retinal arterial occlusion, the rate of stroke/TE/TIA was 8.16 (95% CI 6.35-10.49) per 100 person-years, and for patients with retinal venous occlusion it was 7.28 (95% CI 5.93-8.94) per 100 person-years. In multivariate analysis, both retinal arterial occlusions (hazard ratio [HR] 1.39, 95% CI 1.08-1.79) and retinal venous occlusions (HR 1.26, 95% CI 1.02-1.54) were associated with an increased risk of future stroke/TE/TIA., Conclusions: A history of retinal arterial or retinal venous occlusion is associated with an increased risk of stroke/TE/TIA in patients with atrial fibrillation. Thus, prior retinal vascular occlusion may be considered as a previous thromboembolic event when evaluating stroke risk in patients with atrial fibrillation., (© 2013 International Society on Thrombosis and Haemostasis.)

Chronic Kidney Disease (CKD) constitutes an adverse risk factor in chronic anticoagulated atrial fibrillation (AF) patients, being related to adverse cardiovascular events, mortality and major bleeds. It is unclear if CKD adds independent prognostic information to stroke risk stratification schemes, as the risk factor components of the CHADS2 and CHA2DS2-VASc scores are themselves related to renal dysfunction. The aim of our study was to determine if CKD independently improves the predictive value of the CHADS2 and CHA2DS2-VASc stroke stratification scores in AF. We recruited consecutive patients (n=978) patients (49% male; median age 76) with permanent or paroxysmal AF on oral anticoagulants with acenocoumarol, from our out-patient anticoagulation clinic. After a median follow-up of 875 (IQR 706-1059) days, we recorded stroke/transient ischaemic attack (TIA), peripheral embolism, vascular events (acute coronary syndrome, acute heart failure and cardiac death) and all-cause mortality. During follow-up, 113 patients (4.82%/year) experienced an adverse cardiovascular event, of which 39 (1.66%/year) were strokes, 43 (1.83%/year) had an acute coronary syndrome and 32 (1.37%/year) had acute heart failure. Also, 102 patients (4.35%/year) died during the following up, 31 of them (1.32%/year) as a result of a thrombotic event. Based on c-statistics and the integrated discrimination improvement (IDI), CKD did not improve the prediction for stroke/systemic embolism, thrombotic events and all-cause mortality using the CHADS2 and CHA2DS2-VASc scores. In conclusion, evaluating renal function in AF patients is important as CKD would confer a poor overall prognosis in terms of thromboembolic events and all-cause mortality. Adding CKD to the CHADS2 and CHA2DS2-VASc stroke risk scores did not independently add predictive information.

Background: Atrial fibrillation (AF) is commonly associated with vascular disease. Although atherosclerotic vascular disease (for example, defined as a myocardial infarction (MI), complex aortic plaque and peripheral arterial disease) has been proposed as a risk factor for a stroke, the co-existence of the two diseases increases the risk of future cardiovascular events. The objective of this study was to conduct a systematic review to assess the impact of atherosclerotic vascular disease on the primary end-point of a stroke, thromboembolism or mortality, in patients with AF., Methods: Literature searches were performed electronically, to identify studies published between January 1990and July 2012 examining stroke and thromboembolism in relation to AF and atherosclerotic vascular disease. Nineteen articles satisfied the pre-inclusion criteria. The bibliographies were subsequently screened to retrieve further relevant studies for this review., Results: Peripheral arterial disease significantly increased the stroke risk in all 10 observational studies, within a reported risk range of 1.3- to 2.5-fold. Complex aortic plaque on the descending aorta, as identified by trans-oesophageal echocardiography, was also a significant risk factor. Although a prior myocardial infarction (MI) was validated as a significant predictor of the primary end-point amongst five of the six studies, there was a degree of heterogeneity, owing to the marked difference in population sizes and the use of antithrombotic regimens between studies., Conclusion: Atherosclerotic vascular disease (e.g. peripheral arterial disease, complex aortic plaque and prior MI) are significant predictors of a stroke, thromboembolism and mortality in subjects with AF., (© 2013 International Society on Thrombosis and Haemostasis.)

Background: Female sex has been suggested as a risk factor for stroke/thromboembolism in patients with non-valvular atrial fibrillation (AF) and has therefore been included within risk scores, e.g., the CHA2 DS2 -VASc score, and guidelines., Objectives: To investigate the risk of stroke/thromboembolism associated with female sex in non-valvular AF patients., Patients/methods: Using the national Danish registers, we identified non-anticoagulated patients discharged with non-valvular AF (1997-2008), and subdivided the population into three age intervals: < 65, 65-74 and ≥ 75 years. We calculated stroke rates according to sex, and assessed the stroke risk associated with female sex by using Cox regression analysis., Results: We included 87,202 AF patients, and 44,744 (51.3%) were female. The rate of stroke/thromboembolism for females aged < 65 and 65-74 years was not increased as compared with men, whereas the rate for females aged ≥ 75 years was increased. At both 1-year and 12-year follow-up, female sex did not increase the risk of stroke for patients aged < 75 years. At 1-year follow-up, the hazard ratios associated with female sex were 0.89 (95% confidence interval [CI] 0.70-1.13) and 0.91 (95 CI 0.79-1.05) for patients aged < 65 and 65-74 years, respectively, and being female and aged ≥ 75 years was associated with an increased risk of stroke of 1.20 (95 CI 1.12-1.28)., Conclusion: Female sex was only associated with an increased risk of stroke for AF patients aged ≥ 75 years. Our study suggests that female sex should not be automatically included as an independent stroke/thromboembolic risk factor in guidelines or in the CHA2 DS2 -VASc score, without careful prior consideration of the 'age < 65 and lone AF' criterion., (© 2012 International Society on Thrombosis and Haemostasis.)

Unlabelled: There are limited data on the prognostic role of biomarkers in anticoagulated patients with atrial fibrillation (AF). We evaluated the prognostic value of high sensitivity TnT (hsTnT) and high-sensitivity interleukin-6 (hsIL6) in a large cohort of AF patients taking oral anticoagulant therapy (OAC) as both biomarkers have been associated with adverse cardiovascular events., Methods: We studied 930 patients (51% male; median age 76) with permanent/ paroxysmal AF who were stabilized (for at least 6 months) on OAC (INRs 2.0-3.0). Plasma hsTnT and hsIL6 levels were quantified by electrochemiluminescense immunoassay at baseline. Patients were followed-up for up to 2 years, and adverse events (thrombotic and vascular events, mortality and major bleeding) were recorded., Results: At follow-up, 96 patients (3.97%/year) died whilst 107 had an adverse cardiovascular event (3.14%/year). On multivariate analysis, high hsTnT and high hsIL6 remained significantly associated with prognosis even after adjusting for CHADS2 score: HR 2.21 (1.46-3.35, P<0.001) for high hsTnT and 1.97 (1.29-3.02, P=0.002) for high hsIL6, for adverse cardiovascular events. For all-cause mortality, the HRs were 1.79 (1.13-2.83, P=0.013) and 2.48 (1.60-3.85, P<0.001), respectively. The integrated discrimination index (IDI) values of clinical scores (CHADS2 and CHA2 DS2-VASc) were improved by the addition of hsTnT and/or hsIL6 (all P<0.05)., Conclusion: In a large 'real world' cohort of anticoagulated AF patients, both hsTnT and hsIL6 levels provided prognostic information that was complementary to clinical risk scores for prediction of long-term cardiovascular events and death, suggesting that these biomarkers may potentially be used to refine clinical risk stratification in AF., (© 2012 International Society on Thrombosis and Haemostasis.)

Aim: A network meta-analysis of the three new oral anticoagulants was performed from the three trials comparing dabigatran, rivaroxaban and apixaban with warfarin in patients with atrial fibrillation., Methods: Data were extracted of the RE-LY study of dabigatran 110 mg bid and dabigatran 150 mg bid, the ROCKET AF trial of rivaroxaban and the ARISTOTLE trial of apixaban for the composite outcome of ischemic stroke and systemic embolism, for major bleeding, intracerebral bleeding, mortality and myocardial infarction., Results: Dabigatran (150 mg bid) showed superior efficacy in preventing ischemic stroke plus systemic embolism to dabigatran (110 mg bid, P=0.0364) and rivaroxaban (P=0.0388). Apixaban had equivalent efficacy with rivaroxaban and dabigatran (either dose). Apixaban was safer (less major bleeding) than dabigatran (150 mg bid, P=0.036) or rivaroxaban (P=0.0002). Intracerebral hemorrhage occurred with equal frequency for all agents except for rivaroxaban (higher risk than dabigatran 110 mg bid, P=0.0070). Myocardial infarction occurred less frequently with rivaroxaban and apixaban compared to either dose of dabigatran (all P<0.05)., Conclusion: All-cause mortality was not different for any agent or regimen. In the absence of head-to-head comparisons, this network meta-analysis suggests that apixaban and dabigatran 110 mg bid may offer the best benefit-risk balance for stroke prevention in non-valvular atrial fibrillation. Dabigatran 150 mg bid may be preferred for patients with a high risk for embolism.

The presence of atrial fibrillation (AF) increases the risk of stroke fivefold, but the risk is dependent upon the presence of stroke risk factors. The challenge is defining patients who would best benefit from thromboprophylaxis, and how to deliver it in the most effective and safe way. The objective of this brief overview is to address this question. Previously, attention has been directed towards identifying high-risk patients who could be subjected to an inconvenient (and potentially dangerous) drug, warfarin. Aspirin has been increasingly recognised as an inferior choice for stroke prevention, and may not be any safer than warfarin in terms of major bleeding, especially in the elderly. Thus, the focus more recently has been directed towards identifying truly low-risk patients who do not need any antithrombotic therapy, and all others with ≥ 1 stroke risk factors should be considered for oral anticoagulation therapy (whether as well-controlled warfarin or one of the new oral anticoagulant drugs), as the most effective means of reducing the risk of stroke and thromboembolism in AF.

Background: Oral anticoagulation (OAC) in patients with atrial fibrillation (AF) is a double-edged sword, because it decreases the risk of stroke at the cost of an increased risk of bleeding. We compared the performance of a new bleeding prediction scheme, HAS-BLED, with an older bleeding prediction scheme, HEMORR(2)HAGES, in a cohort of 'real-world' AF patients., Methods: By individual-level-linkage of nationwide registers, we identified all patients (n = 118,584) discharged with non-valvular AF in Denmark during the period 1997-2006, with and without OAC. Major bleeding rates during 1 year of follow-up were determined, and the predictive capabilities of the two schemes were compared by c-statistics. The risk of bleeding associated with individual risk factors composing HAS-BLED was estimated using Cox proportional-hazard analyses., Results: Of AF patients receiving OAC (n = 44,771), 34.8% and 47.3% were categorized as 'low bleeding risk' by HAS-BLED and HEMORR(2)HAGES, respectively, and the bleeding rates per 100 person-years were 2.66 (95% confidence interval [CI], 2.40-2.94) and 3.06 (2.83-3.32), respectively. C-statistics for the two schemes were 0.795 (0.759-0.829) and 0.771 (0.733-0.806), respectively. The risk factors composing HAS-BLED were associated with varying risks, with a history of bleeding (hazard ratio [HR] 2.98; 95% CI 2.68-3.31) and being elderly (HR 1.93; 95% CI 1.71-2.18) being associated with the highest risks. Comparable results were found in AF patients not receiving OAC (n = 77,813)., Conclusions: In an unselected nationwide cohort of hospitalized patients with atrial fibrillation, the HAS-BLED score performs similarly to HEMORR(2)HAGES in predicting bleeding risk but HAS-BLED is much simpler and easier to use in everyday clinical practise., (© 2011 International Society on Thrombosis and Haemostasis.)

Atrial fibrillation (AF) is the commonest sustained cardiac rhythm disorder, which is associated with a substantial risk of mortality and morbidity arising from stroke and thromboembolism. Extensive epidemiological evidence and robust data from clinical trials have shown that stroke and thromboembolism in AF can be prevented by oral anticoagulation (OAC). Despite this evidence and guidelines, appropriate thromboprophylaxis is still suboptimal, and this is partly due to the only OAC agent being available is the vitamin K antagonist class of drugs (e.g. warfarin) that has many limitations and disadvantages. With the availability of new OAC agents that avoid the disutility of the vitamin K antagonists, it is hoped that greater use of OAC would allow more effective thromboprophylaxis and have a great impact on preventing strokes related to AF. Additionally, stroke risk assessments need to evolve such that they are better at identifying the 'truly low risk' subjects who do not need antithrombotic therapy, whilst all other patients with ≥ 1 stroke risk factors can be considered for OAC. The availability of comprehensive stroke and bleeding risk assessments would enable us to make informed decisions in everyday clinical practice. The aim of the review article is to provide a state-of-the-art overview of the clinical epidemiology of stroke in AF, stroke (and bleeding) risk assessments and the current provision of thromboprophylaxis for patients with AF., (© 2011 International Society on Thrombosis and Haemostasis.)

Background: The presence of vascular disease (peripheral artery disease [PAD] and/or myocardial infarction [MI]) may impact on the risk of stroke and death among patients with incident atrial fibrillation (AF). To test this hypothesis, we analyzed data from a large Danish prospective cohort, the Danish Diet, Cancer and Health (DCH) study, to assess the risk of stroke or death among those who developed AF according to concomitant presence of vascular disease., Methods: A prospective cohort study of 57, 053 persons (27, 178 men and 29, 876 women, respectively), aged between 50 and 64 years. The risk of stroke or death for patients with vascular disease was assessed amongst 3315 patients with incident AF (mean age, 67.1years; 2130 men, 1185 women) using Cox proportional hazard models, after a median follow-up of 4.8 years., Results:  Of the subjects with AF, 417 (12.6%) had 'vascular disease' (PAD and/or prior MI). The risk of the primary endpoint (stroke or death) was significantly higher in patients with vascular disease at 1-year follow-up (crude hazard ratio [HR] 2.51 [1.91-3.29]), with corresponding crude HRs for PAD and MI being 3.51 (2.40-5.13), and 1.99 (1.46-2.72), respectively. For the secondary endpoints of death or stroke individually, these risk estimates were similar (crude HR 2.48 [1.89-3.26] and 1.77 [1.18-2.66], respectively). After adjustment for risk factors within the CHADS(2) score, the adjusted HR for the primary endpoint (stroke or death) in patients with vascular disease was 1.91 (1.44-2.54), which was also significant for death (1.97 [1.48-2.62])., Conclusion: Vascular disease (prior MI and PAD) is an independent risk factor for the primary endpoint of 'stroke or death' in patients with AF, even after adjustment for the CHADS(2) risk score, although this is driven by the impact on mortality. This reaffirms that patients with vascular disease represent a 'high-risk' population, which necessitates proactive management of all cardiovascular risk factors and effective thromboprophylaxis (i.e. oral anticoagulation), which has been shown to significantly reduce the risk of stroke and death in AF., (© 2011 International Society on Thrombosis and Haemostasis.)

Objective: To compare the predictive power of the main existing and recently proposed schemes for stratification of risk of stroke in older patients with atrial fibrillation., Design: Comparative cohort study of eight risk stratification scores., Setting: Trial of thromboprophylaxis in stroke, the Birmingham Atrial Fibrillation in the Aged (BAFTA) trial., Participants: 665 patients aged 75 or over with atrial fibrillation based in the community who were randomised to the BAFTA trial and were not taking warfarin throughout or for part of the study period., Main Outcome Measures: Events rates of stroke and thromboembolism., Results: 54 (8%) patients had an ischaemic stroke, four (0.6%) had a systemic embolism, and 13 (2%) had a transient ischaemic attack. The distribution of patients classified into the three risk categories (low, moderate, high) was similar across three of the risk stratification scores (revised CHADS(2), NICE, ACC/AHA/ESC), with most patients categorised as high risk (65-69%, n = 460-457) and the remaining classified as moderate risk. The original CHADS(2) (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke) score identified the lowest number as high risk (27%, n = 180). The incremental risk scores of CHADS(2), Rietbrock modified CHADS(2), and CHA(2)DS(2)-VASc (CHA(2)DS(2)-Vascular disease, Age 65-74 years, Sex) failed to show an increase in risk at the upper range of scores. The predictive accuracy was similar across the tested schemes with C statistic ranging from 0.55 (original CHADS(2)) to 0.62 (Rietbrock modified CHADS(2)), with all except the original CHADS(2) predicting better than chance. Bootstrapped paired comparisons provided no evidence of significant differences between the discriminatory ability of the schemes., Conclusions: Based on this single trial population, current risk stratification schemes in older people with atrial fibrillation have only limited ability to predict the risk of stroke. Given the systematic undertreatment of older people with anticoagulation, and the relative safety of warfarin versus aspirin in those aged over 70, there could be a pragmatic rationale for classifying all patients over 75 as "high risk" until better tools are available.

Cardioembolism accounts for approximately 20% of ischaemic strokes, and is associated with high mortality and propensity to recurrences. Approximately, 30% of ischaemic strokes remain cryptogenic despite improved imaging modalities and technological improvements to identify their cause. Of the long list of various cardiac conditions associated with an increased risk of cardioembolic strokes, non-valvular atrial fibrillation is the most common cause. Unsurprisingly, the stroke risk associated with these conditions is highly variable and non-homogenous, with many risk factors additive to the overall risk profile. Treatment with vitamin K-antagonists substantially reduces the long-term complications associated with cardioembolism in some high-risk patients, for example, in atrial fibrillation. Careful selection of antithrombotic drug regime needs to be carried out in patients individually to minimise the risk of bleeding encountered with such therapy. Apart from atrial fibrillation, there is relatively limited evidence for the role of antithrombotic therapy for other cardiac conditions associated with cardioembolism and how long one should treat.

Aims: To test the hypothesis that stroke and systemic embolic events (SEE) in the stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) III and V trials are different between paroxysmal and persistent atrial fibrillation (AF)., Methods: Data analysis from two cohorts of patients enrolled in the prospective SPORTIF III and V clinical trials (n = 7329); 836 subjects (11.4%) with paroxysmal AF [mean age 70.1 years (SD = 9.5)] were compared with 6493 subjects with persistent AF for this ancillary study., Results: The annual event rates for stroke/SEE are 1.73% for persistent AF and 0.93% for paroxysmal AF. In a multivariate analysis, after adjusting for stroke risk factors, gender and aspirin usage, the differences remained statistically significant with a higher hazard ratio (HR) for stroke/SEE in persistent AF [vs. paroxysmal AF, HR 1.87, 95% confidence interval (CI) 1.04-3.36; P = 0.037]. In 'high risk' patients (with >or=2 stroke risk factors) annual event rates for stroke/SEE were 2.08% for persistent AF and 1.27% for paroxysmal AF (adjusted HR = 1.68, 95% CI 0.91-3.1, P = 0.098). Elderly patients had annual event rates for stroke/SEE of 2.38% for persistent AF and 1.13% for paroxysmal AF (adjusted HR = 2.27, 95% CI 0.92-5.59, P = 0.075). Vitamin K antagonist (VKA)-naive paroxysmal AF patients had a 1.89%/year stroke/SEE rate, compared with 0.61% for previous VKA takers (HR = 0.33, 95% CI 0.11-1.01, P = 0.052)., Conclusion: In this large clinical trial cohort of anticoagulated AF patients, those with paroxysmal AF had stroke rates which were lower than for patients with persistent AF, although both groups had broadly similar stroke risk factors. Subjects with paroxysmal AF at 'high risk' had stroke/SEE rates that were not significantly different to persistent AF subjects.

Background: Stroke is a major cause of premature mortality in Britain, but its burden is markedly greater amongst South Asians. Because of the paucity of data in this area, we investigated the magnitude and impact of risk from cardiovascular comorbidities on survival amongst South Asian stroke patients., Methods: We reviewed hospital case records of consecutive first in life time ischaemic stroke patients [self reported ethnicity and International Classification of Disease (ICD) 10th revision, codes 430-438] admitted to an inner city hospital in the UK between 1997 and 2001. In-hospital mortality data and CVD risk factors were analysed. Five-year mortality data was obtained from the National Health Tracing Services., Results: Of 1474 ischaemic stroke patients, 242 (16%) were South Asian of whom, 143 (59.1%) were male. The prevalence of hypertension was 70.2%, followed by diabetes 56.2%, hyperlipidaemia 7% and myocardial infarction 10.3%. At 5 years follow-up, 40.5% had died. Cumulative event-free survival at 5 years was significantly poorer in patients with diabetes (log-rank test, p=0.009). On Cox regression analysis, incorporating age, gender and other CVD risk factors, diabetes mellitus was an independent predictor of mortality odds ratio=1.65 (1.02-2.6, p=0.039). Hypertension and dyslipidaemia did not discriminate survival amongst South Asian patients., Conclusion: Stroke mortality in South Asians is associated with presence of diabetes mellitus. This highlights the significance of early and intensive CVD risk modification strategies in ethnic minorities particularly in patients with diabetes. Further research is warranted in South Asians to examine the underlying basis and related pathophysiological abnormalities.

Our objective was to study ethnic differences in the cardiovascular risk profile and mortality of stroke admissions to an inner city teaching hospital serving a multiethnic population in Birmingham, UK, over a 9-year period (1997-2005). Hospital case notes and registry data of 3083 patients admitted with a first onset stroke were reviewed. Secular trends in the prevalence of risk factors (hypertension, diabetes, hyperlipidaemia, atrial fibrillation and myocardial infarction), hospital admission rates and 30-day mortality among Afro-Caribbean, European Caucasian and South Asian ethnic groups were analysed. Between 1997 and 2005, there were 3083 first onset strokes, of whom 47.6% (1595) were men, 9.3% Afro-Caribbean, 57.8% European Caucasian and 15.1% South Asian. There was a significant trend towards a reduction in non-haemorrhagic stroke admissions over the study period (P<0.001), with no ethnic variation (P=0.07). Increases in hypertension and hyperlipidaemia were observed (P<0.001), whereas myocardial infarction showed a decline (P<0.001). Compared to other ethnic groups, South Asian patients were younger on admission (P<0.001), had more hyperlipidaemia (P<0.05) and poorer survival at 30 days (P=002). We conclude that cardiovascular risk profiles among patients admitted with non-haemorrhagic stroke have changed over the last decade. In particular, hyperlipidaemia has increased, especially among South Asians. The reduced decline in stroke admissions and 30-day survival of stroke in South Asians in recent years warrants further investigation and highlights the importance of a targeted health-care approach in the migrant ethnic minorities.

Abnormalities of haemorheology (plasma viscosity, fibrinogen), endothelial function [von Willebrand factor (vWf)], platelet activation (soluble P-selectin) and thrombogenesis [plasminogen activator inhibitor (PAI), and fibrin D-dimer] are common in cardiovascular disease. We investigated changes in these markers in 86 patients (58 males) presenting with acute stroke (all age < 75 years, with ictus < 12 h), and sequential changes at six time points (baseline on admission, 48 h, 1 week, 2 weeks, 3 months and 6 months following the onset of stroke). Baseline plasma viscosity, haematocrit, fibrinogen, vWf, PAI, soluble P-selectin and fibrin D-dimer levels were increased in the acute stroke patients compared with 35 age-matched and sex-matched controls. Following admission, there were significant increases in haematocrit at 2 weeks, vWf at 48 h and 1 week, fibrinogen at 1 week, PAI at 48 h and 1 and 2 weeks, soluble P-selectin at 48 h, and fibrin D-dimer at 48 h and 1 week following admission. Using univariate 'time to event' analysis, high (> median) mean age (log-rank test, P = 0.0262), diastolic blood pressure (P = 0.01), haematocrit (P = 0.0234), PAI-1 (P = 0.0066) and fibrin D-dimer levels (P = 0.0356) were associated with a shortened event-free survival. Using a multivariate Cox survival analysis, only PAI-1 levels remained an independent predictor of survival (P = 0.0349). We conclude that acute stroke patients have marked baseline abnormalities of haemorheology, endothelial disturbance, thrombogenesis, platelet activation and abnormal fibrinolysis, with further changes over the subsequent follow-up period. Abnormal thrombogenesis and fibrinolysis may significantly influence survival in patients with acute stroke. These changes may have potential implications for the pathogenesis of stroke and its complications, although the possibility remains that we are documenting an acute phase response that previous studies, which included stroke patients with a wide time range since ictus onset, have neglected to consider.