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Background: Transient ischemic attack (TIA) is a strong signal prompting the incidence of future cardiovascular and non-cardiovascular complications, in light of recent debate on the so-called "stroke-heart syndrome." We aimed to investigate the relation of TIAs to incident clinical events., Methods: Patients were drawn from three health plans with a wide spectrum of age groups and a wide mix of socio-economic/disability status. Two TIA cohorts in a retrospective design were used to achieve the study specific aims: (i) to investigate the incidence of TIA and associated cardiovascular and non-cardiovascular complications within 30 and 90 days from the onset of incident TIA events; and (ii) to examine the potential risk factors for developing incident TIA events in the general population with/without a history of prior stroke., Results: The incident TIA cohort consisted of 53,716 patients with an average age of 64.2 years (SD 15.2) and 46.1% male. Following TIA, the incidence proportions of ischemic stroke within 30 and 90 days were 2.7% and 3.8%, respectively, and for incident acute coronary syndrome being 0.94 and 1.84, respectively. Ventricular arrhythmia had proportions of 1.2 and 2.14, respectively within 30 and 90 days, with acute heart failure having values of 0.49 and 0.923. About 45% or more of the cardiovascular and non-cardiovascular complications occurred in the first 30 days following the incident TIA cases. About one-third of the recurrent TIA cases followed the incident TIA cases within a span of 30 days. Amongst comorbidities with stroke in the comorbid history, prior stroke provided the strongest risk factor in terms of odds ratio (OR = 8.34, 95% CI 7.21-9.66) for incident TIA events. Age was strongly associated with incident TIA events. Without a prior history of stroke (ischemic stroke/transient ischemic attack/thrombo-embolic events), valvular disease was the strongest risk factor from among the comorbidities (OR-1.87, 95% CI 1.51-2.32). Age also provided strong associations with incident TIA events., Conclusions: Following a TIA, there was a high risk of stroke, acute coronary syndrome, ventricular arrhythmia, acute heart failure, and non-cardiovascular complications., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: the authors report no conflicts of interest in relation to this work. GYHL has been a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthem. No fees are received personally. GYHL is co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 899871., (© European Stroke Organisation 2022.)

Background: Several molecular biomarkers are available that predict newly detected atrial fibrillation (NDAF). We aimed to identify such biomarkers that predict NDAF after an Ischaemic stroke (IS)/Transient Ischaemic Attack (TIA) and evaluate their performance., Methods: A systematic review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies of patients with IS, TIA, or both, who underwent ECG monitoring for ⩾24 h, which reported molecular biomarkers and frequency of NDAF after electronic searches of multiple databases were included., Results: Twenty-one studies (76% IS, 24% IS and TIA) involving 4640 patients were included. Twelve biomarkers were identified, with cardiac biomarkers evaluated in the majority (75%) of patients. Performance measures were inconsistently reported. Among cohorts selecting high-risk individuals (12 studies), the most studied biomarkers were N-Terminal-Pro Brain Natriuretic Peptide (NT-ProBNP, five studies; C-statistics reported by three studies, 0.69-0.88) and Brain Natriuretic Peptide (BNP, two studies; C-statistics reported in two studies, 0.68-0.77). Among unselected cohorts (nine studies), the most studied biomarker was BNP (six studies; C-statistics reported in five studies, 0.75-0.88). Only BNP was externally validated (two studies) but using different thresholds to categorise risk of NDAF., Conclusion: Cardiac biomarkers appear to have modest to good discrimination for predicting NDAF, although most analyses were limited by small, heterogeneous study populations. Their clinical utility should be explored further, and this review supports the need to assess the role of molecular biomarkers in large prospective studies with standardised selection criteria, definition of clinically significant NDAF and laboratory assays., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JD has obtained honoraria from Medtronic, BI, BMS, Diaicchi Sankyo, Bayer, Pfizer. In addition, research support was also obtained from Pfizer and BMS. AK has obtained honoraria from Medtronic, Bayer and Abbott Inc. AC has received honoraria from BMS, Pfizer, AstraZeneca and Boeringher Ingelheim and research grants from Pfizer., (© European Stroke Organisation 2022.)

Background: Treatment decisions about oral anticoagulants (OACs) for atrial fibrillation (AF) are complex in older care home residents., Aim: To explore factors associated with OAC prescription., Design and Setting: Retrospective cohort study set in care homes in Wales, UK, listed in the Care Inspectorate Wales Registry 2017/18., Method: Analysis of anonymised individual-level electronic health and administrative data was carried out on people aged ≥65 years entering a care home between 1 January 2003 and 31 December 2018, provisioned from the Secure Anonymised Information Linkage Databank., Results: Between 2003 and 2018, 14 493 people with AF aged ≥65 years became new residents in care homes in Wales and 7057 (48.7%) were prescribed OACs (32.7% in 2003 compared with 72.7% in 2018) within 6 months before care home entry. Increasing age and prescription of antiplatelet therapy were associated with lower odds of OAC prescription (adjusted odds ratio [aOR] 0.96 per 1-year age increase, 95% confidence interval [CI] = 0.95 to 0.96 and aOR 0.91, 95% CI = 0.84 to 0.98, respectively). Conversely, prior venous thromboembolism (aOR 4.06, 95% CI = 3.17 to 5.20), advancing frailty (mild: aOR 4.61, 95% CI = 3.95 to 5.38; moderate: aOR 6.69, 95% CI = 5.74 to 7.80; and severe: aOR 8.42, 95% CI = 7.16 to 9.90), and year of care home entry from 2011 onwards (aOR 1.91, 95% CI = 1.76 to 2.06) were associated with higher odds of an OAC prescription., Conclusion: There has been an increase in OAC prescribing in older people newly admitted to care homes with AF. This study provides an insight into the factors influencing OAC prescribing in this population., (© The Authors.)

Background: Balancing the risk of thromboembolism and bleeding in patients with liver disease and atrial fibrillation/flutter is particularly challenging., Purpose: To examine the risks of thromboembolism and bleeding with use/non-use of oral anticoagulation (including vitamin K-antagonists and direct oral anticoagulants) in patients with liver disease and AF., Methods: Danish nationwide register-based cohort study of anticoagulant naive individuals with liver disease, incident atrial fibrillation/flutter, and a CHA 2 DS 2 -VASc-score≥1 (men) or ≥2 (women), alive 30 days after atrial fibrillation/flutter diagnosis. Thromboembolism was a composite of ischaemic stroke, transient ischaemic attack, or venous thromboembolism. Bleeding was a composite of gastrointestinal, intracerebral, or urogenital bleeding requiring hospitalisation, or epistaxis requiring emergency department visit or hospital admission. Cause-specific Cox-regression was used to estimate absolute risks and average risk ratios standardised to covariate distributions. Because of significant interactions with anticoagulants, results for thromboembolism were stratified for CHA2DS2-VASc-score, and results for bleeding were stratified for cirrhotic/non-cirrhotic liver disease., Results: Four hundred and nine of 1,238 patients with liver disease and new atrial fibrillation/flutter initiated anticoagulants. Amongst patients with a CHA2DS2-VASc-score of 1-2 (2-3 for women), five-year thromboembolism incidence rates were low and similar in the anticoagulant (6.5%) versus no anticoagulant (5.5%) groups (average risk ratio 1.19 [95%CI, 0.22-2.16]). In patients with a CHA2DS2-VASc-score>2 (>3 for women), incidence rates were 16% versus 24% (average risk ratio 0.66 [95%CI, 0.45-0.87]). Bleeding risks appeared higher amongst patients with cirrhotic versus non-cirrhotic disease but were not significantly affected by anticoagulant status., Conclusion: Oral anticoagulant initiation in patients with liver disease, incident new atrial fibrillation/flutter, and a high CHA2DS2-VASc-score was associated with a reduced thromboembolism risk. Bleeding risk was not increased with anticoagulation, irrespective of the type of liver disease., 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 © 2022 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Aim: To investigate the association between medication use and long-term all-cause mortality in a Brazilian stroke cohort., Methods: Both ischemic and hemorrhagic stroke were evaluated. Medication use was assessed as: never, only pre-stroke, only post-stroke, and continuous use. We evaluated anti-hypertensives, anti-diabetics, lipid-lowering drugs, anti-platelets, and anti-coagulants. Cox regression models were adjusted for sociodemographic and cardiovascular risk factors., Results: Among 1173 incident stroke cases (median age: 68; 86.8% were ischemic, 70% first-ever stroke), medication use was low (overall: 17.5% pre-stroke, 26.4% post-stroke, and 40% were under continuous use). Anti-hypertensives and anti-platelets (aspirin) were the continuous cardiovascular medications used most often, at 83.5% and 72%, respectively, while statins (39.7%) and anti-diabetics (31.3%) were the least used. Medication use (pre-stroke, post-stroke and continuous use) was associated with a reduction in all-cause mortality risk, particularly among those under continuous use (multivariable hazard ratio, 0.52; 95% confidence interval (CI), 0.46-0.66) compared with never-users. Among ischemic stroke patients, this effect was similar (multivariable hazard ratio, 0.52; 95% CI, 0.40-0.68). No significant associations were evident among hemorrhagic stroke patients., Conclusions: The risk of all-cause mortality was reduced by 48% among those with ischemic stroke under continuous use of medications. Secondary prevention should be emphasized more strongly in clinical practice. Geriatr Gerontol Int 2022; 22: 715-722., (© 2022 Japan Geriatrics Society.)

Frailty is a clinical syndrome characterized by a reduced physiologic reserve, increased vulnerability to stressors and an increased risk of adverse outcomes. People with atrial fibrillation (AF) are often burdened by frailty due to biological, clinical, and social factors. The prevalence of frailty, its management and association with major outcomes in AF patients are still not well quantified. We systematically searched PubMed and EMBASE, from inception to September 13th, 2021, for studies reporting the prevalence of frailty in AF patients. The study was registered in PROSPERO (CRD42021235854). 33 studies were included in the systematic review (n = 1,187,651 patients). The frailty pooled prevalence was 39.7 % (95 %CI=29.9 %-50.5 %, I 2 =100 %), while meta-regression analyses showed it is influenced by age, history of stroke, and geographical location. Meta-regression analyses showed that OAC prescription was influenced by study-level mean age, baseline thromboembolic risk, and study setting. Frail AF patients were associated with a higher risk of all-cause death (OR=5.56, 95 %CI=3.46-8.94), ischemic stroke (OR=1.59, 95 %CI=1.00-2.52), and bleeding (OR=1.64, 95 %CI=1.11-2.41), when compared to robust individuals. In this systematic review and meta-analysis, the prevalence of frailty was high in patients with AF. Frailty may influence the prognosis and management of AF patients, thus requiring person-tailored interventions in a holistic or integrated approach to AF care., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Advancing age is a major risk factor for ischemic stroke in atrial fibrillation. We aimed to evaluate the predictors of all-cause death/any thromboembolism and the impact of oral anticoagulant on clinical outcomes in very elderly (≥85 years) Chinese atrial fibrillation patients., Methods: The ChiOTEAF is a prospective registry proceeded in 44 sites from 20 provinces in China between October 2014 and December 2018. Outcomes of interest were all-cause mortality, any thromboembolism, major bleeding, and new onset/worsening heart failure., Results: The eligible cohort for this analysis included 6416 patients and 1215 (18.9%) patients were aged ≥85 years. Only 320 (26.4%) very elderly patients were treated with oral anticoagulant, of whom 205 (64.1%) received non-vitamin K antagonist oral anticoagulants, while antiplatelet therapy was used among 642 (53.1%) very elderly patients. On multivariate analysis, the use of oral anticoagulant was an independent predictor of a lower risk of the composite outcome (OR: 0.46; 95% CI: 0.32-0.66) and all-cause death (OR: 0.47; 95% CI: 0.32-0.69) among these very elderly atrial fibrillation patients., Conclusions: Advanced age should not be a reason to withhold oral anticoagulant, since the use of oral anticoagulants is safe and improves survival.

Background and Purpose: The effectiveness and safety of edoxaban 60 mg and 30 mg for stroke prevention compared with warfarin in patients with atrial fibrillation have not been well-described in a nationwide cohort of Caucasian patients treated in standard clinical practice., Methods: We used Danish nationwide registries to identify patients with atrial fibrillation during June 2016 and November 2018 who were treated with edoxaban or warfarin and computed rates per 100 person-years of thromboembolic, all-cause mortality, and bleeding events using an inverse probability of treatment weighting approach to account for baseline confounding. We used weighted pooled logistic regression to compute hazard ratios with 95% confidence intervals comparing events between edoxaban 60 mg and warfarin users; edoxaban 30 mg was not included in formal comparisons., Results: We identified 6451 atrial fibrillation patients, mean age was 72 years and 40% were females. A total of 1772 patients were treated with edoxaban 60 mg, 537 with edoxaban 30 mg, and 4142 with warfarin. The median CHA 2 DS 2 -VASc score was similar between warfarin and edoxaban 60 mg with a score of 3 (interquartile range (IQR) 2-4). In the inverse probability of treatment-weighted pseudo-population, the thromboembolic event rate for edoxaban 60 mg was 0.95 and 1.0 for warfarin, corresponding weighted hazard ratio of 1.00 (95% confidence intervals (CI) 0.59, 1.71). Edoxaban 60 mg users were associated with lower rates of all-cause mortality (3.93) compared to warfarin (6.04), with a hazard ratio of 0.64 (95% CI 0.47 to 0.88). The event rates for bleeding were 3.36 and 3.14, respectively; hazard ratio 1.09 (95% CI 0.77, 1.57)., Conclusion: Edoxaban 60 mg is a safe and effective treatment compared with warfarin for stroke prevention in routine clinical care for Danish (mainly Caucasian) patients with AF, with non-significantly different risks for stroke and clinically relevant bleeding, but lower all-cause mortality.

Rationale: Atrial fibrillation causes one-fifth of ischemic strokes, with a high risk of early recurrence. Although long-term anticoagulation is highly effective for stroke prevention in atrial fibrillation, initiation after stroke is usually delayed by concerns over intracranial hemorrhage risk. Direct oral anticoagulants offer a significantly lower risk of intracranial hemorrhage than other anticoagulants, potentially allowing earlier anticoagulation and prevention of recurrence, but the safety and efficacy of this approach has not been established., Aim: Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) will investigate whether early treatment with a direct oral anticoagulant, within four days of stroke onset, is as effective or better than delayed initiation, 7 to 14 days from onset, in atrial fibrillation patients with acute ischemic stroke., Methods and Design: OPTIMAS is a multicenter randomized controlled trial with blinded outcome adjudication. Participants with acute ischemic stroke and atrial fibrillation eligible for anticoagulation with a direct oral anticoagulant are randomized 1:1 to early or delayed initiation. As of December 2021, 88 centers in the United Kingdom have opened., Study Outcomes: The primary outcome is a composite of recurrent stroke (ischemic stroke or symptomatic intracranial hemorrhage) and systemic arterial embolism within 90 days. Secondary outcomes include major bleeding, functional status, anticoagulant adherence, quality of life, health and social care resource use, and length of hospital stay., Sample Size Target: A total of 3478 participants assuming event rates of 11.5% in the control arm and 8% in the intervention arm, 90% power and 5% alpha. We will follow a non-inferiority gatekeeper analysis approach with a non-inferiority margin of 2 percentage points., Discussion: OPTIMAS aims to provide high-quality evidence on the safety and efficacy of early direct oral anticoagulant initiation after atrial fibrillation-associated ischemic stroke. Trial registrations: ISRCTN: 17896007; ClinicalTrials.gov: NCT03759938.

Background: Atrial fibrillation is a predictor of poor prognosis after stroke., Aims: To evaluate atrial fibrillation and all-cause and cardiovascular mortality in a stroke cohort with low socioeconomic status, taking into consideration oral anticoagulant use during 12-year follow-up., Methods: All-cause mortality was analyzed by Kaplan-Meier survival curve and Cox regression models to estimate hazard ratios and 95% confidence intervals (95% CI). For specific mortality causes, cumulative incidence functions were computed. A logit link function was used to calculate odds ratios (OR) with 95% CIs. Full models were adjusted by age, sex, oral anticoagulant use (as a time-dependent variable) and cardiovascular risk factors., Results: Of 1121 ischemic stroke participants, 17.8% had atrial fibrillation. Overall, 654 deaths (58.3%) were observed. Survival rate was lower (median days, interquartile range-IQR) among those with atrial fibrillation (531, IQR: 46-2039) vs . non-atrial fibrillation (1808, IQR: 334-3301), p -log rank < 0.0001). Over 12-year follow-up, previous atrial fibrillation was associated with increased mortality: all-cause (multivariable hazard ratios, 1.82; 95% CI: 1.43-2.31) and cardiovascular mortality (multivariable OR, 2.07; 95% CI: 1.36-3.14), but not stroke mortality. In the same multivariable models, oral anticoagulant use was inversely associated with all-cause mortality (oral anticoagulant time-dependent effect: multivariable hazard ratios, 0.47; 95% CI: 0.30-0.50, p  = 0.002) and stroke mortality (oral anticoagulant time-dependent effect ≥ 6 months: multivariable OR, 0.09; 95% CI: 0.01-0.65, p -value = 0.02), but not cardiovascular mortality., Conclusions: Among individuals with low socioeconomic status, atrial fibrillation was an independent predictor of poor survival, increasing all-cause and cardiovascular mortality risk. Long-term oral anticoagulant use was associated with a markedly reduced risk of all-cause and stroke mortality.

Background: Left atrial thrombus (LAT) often complicates with atrial fibrillation (AF). The evidence whether fibrin D-dimer levels could be used as a predictive biomarker for LAT is contradictory. This study firstly investigated the relationship between 'normal range' D-dimer and prevalent LAT. Second, we explored factors contributing to normal D-dimer levels in the presence of LAT., Methods: We studied 244 AF patients with LAT (mean age: 59.9 years, SD:11.7; 53.3% female): of these, 103 (42.2%) had normal D-dimer, 25 (10.2%) had atrial thrombus exclusion score (ATE score) of 0 19 (16.7%) males had CHA 2 DS 2 -VASc score of 0, 21(16.2%) females had CHA 2 DS 2 -VASc score of 1 and 16 had overlapped ATE score of 0 and CHA 2 DS 2 -VASc score of 0 (N = 8 if male) or CHA 2 DS 2 -VASc score of 1(N = 8 if female). Using multivariate binary analysis, larger left atrial diameter (LAD; adjusted OR: 1.06, 1.03-1.10, p = 0.001) were associated with increased D-dimer. Patients with high body mass index (BMI), hypertension history and previous anticoagulation were more likely to show normal range D-dimer levels in the presence of LAT., Conclusions: A high prevalence (42.2%) of 'normal range' D-dimer levels was found in AF patients with LAT, especially in those with hypertension, high BMI and prior anticoagulation. D-dimer levels of those patients with larger LAD were more likely to be increased.

Background: The 4S-AF scheme includes stroke risk, symptoms, severity of burden, and substrate severity domain., Aim: We aimed to assess the adherence to the 4S-AF scheme in patients classified according to stroke risk in post hoc analysis of the BALKAN-AF dataset., Methods: A 14-week prospective enrolment of consecutive patients with electrocardiographically documented atrial fibrillation (AF) was performed in seven Balkan countries from 2014 to 2015., Results: Low stroke risk (CHA2DS2-VASc score, 0 in males or 1 in females) was present in 162 (6.0%) patients. 2 099 (77.4%) patients had CHA2DS2-VASc score ≥3 in females or ≥2 in males (high stroke risk), and 613 (22.6%) had CHA2DS2-VASc score <3 in females or <2 in males. Seventy-five (46.3%) patients with low stroke risk and 1555 (74.1%) patients with high stroke risk were prescribed oral anticoagulants (OAC). Two thousand six hundred and seventy-seven (98.6%) had data on European Heart Rhythm Association (EHRA) class. Among 2099 patients with high stroke risk, 703 (33.4%) had EHRA class ≥3. Two hundred and seven (29.4%) patients with EHRA class ≥3 and high stroke risk were offered rhythm control; 620 (55.2%) of individuals with first-diagnosed or paroxysmal AF with high stroke risk were offered rhythm control. Two or more comorbidities occurred in 1927 (91.8%) patients with high stroke risk., Conclusions: OAC overuse was observed in patients with low stroke risk, whilst OAC underuse was evident in those with high risk of stroke. The percentage of highly symptomatic patients with high risk of stroke who were offered a rhythm control strategy was low.

Background: Atrial High Rate Episodes (AHRE) are asymptomatic atrial tachy-arrhythmias detected through continuous monitoring with a cardiac implantable electronic device. The risks of stroke/Thromboembolic (TE) events and incident clinical Atrial Fibrillation (AF) associated with AHRE varies markedly., Objectives: To assess the relationship between AHRE and TE events, and between AHRE and incident clinical AF., Methods: This systematic review and meta-analysis was conducted following the PRISMA recommendations. PubMed, Scopus, and Google Scholar were searched from inception to 18/02/2021 for studies reporting TE events and incident clinical AF in patients with AHRE, as compared with patients without., Results: Ten out of 8081 records fulfilled the inclusion criteria, for a total of 37 266 patients. Seven out of ten studies excluded patients with prior history of clinical AF (4961 patients), embracing the most recent definition of AHRE. The risk ratio (RR) for TE events in AHRE patients was 2.13 (95% CI: 1.53-2.95, I 2 : 0%). The incidence of clinical AF was reported in four studies excluding patients with a history of clinical AF (3574 patients). The RR for incident clinical AF was 3.34 (95%CI: 1.89-5.90, I 2 : 73%)., Conclusions: AHRE are significantly associated with systemic thromboembolism and incident clinical AF. Further studies are needed to improve patients' risk stratification and management., (Copyright © 2021. Published by Elsevier B.V.)

The most recent atrial fibrillation (AF) guidelines delivered by European Society of Cardiology (ESC) offer an updated approach to AF management, with the perspective of improved characterization of the arrhythmia, the cardiac substrate and the patients profile in terms of associated risk factors and comorbidities. Recommendations were based on careful scrutiny and assessment of all available evidence with the final aim to offer to practitioners a lower level of uncertainty in the complex process of decision making for patients with AF. The 2020 ESC guidelines on AF propose a paradigm shift in the clinical approach to AF patients, moving from a single-domain AF classification to comprehensive characterization of AF patients. Given the complex nature of AF, an integrated holistic management of AF patients is suggested by the guidelines for improving patients outcomes through the formal introduction of the CC (Confirm AF and Characterize AF) to ABC (Atrial fibrillation Better Care) pathway. In line with this concept, these new guidelines underline the importance of a more comprehensive management of AF patients which should not be limited to simply prescribe oral anticoagulation or decide between a rhythm or rate control strategy. Indeed, each step of the ABC pathway represents one of the pivotal pillars in the management of AF and only a holistic approach has the potential to improve patients' outcomes. In this review we will discuss the background that supports some of the new recommendations of 2020 ESC guidelines, with important implications for daily management of AF patients., (Copyright © 2021. Published by Elsevier B.V.)

Background: Albuminuria level is associated with cardiovascular events and mortality in patients with diabetes. However, little is known about the association between albuminuria level in diabetes patients without overt cardiovascular disease. We aimed to examine the association between albuminuria level and the risk of ischemic stroke, myocardial infarction, and all-cause mortality in patients with type 2 diabetes without overt cardiovascular disease., Methods: We linked Danish nationwide registries to identify patients with type 2 diabetes without cardiovascular disease from May 2005 through June 2015. Patients were followed for the outcomes ischemic stroke, myocardial infarction, and all-cause mortality until December 31, 2015. Albuminuria level was based on 2 consecutive measurements of the urinary albumin excretion rate or albumin-to-creatinine ratio. Associations between albuminuria level and incidence of cardiovascular disease and mortality were evaluated with Cox proportional hazard regression., Results: The study population consisted of 69,532 patients with type 2 diabetes without cardiovascular disease. When comparing patients with microalbuminuria to patients with normoalbuminuria, in an analysis adjusted for cardiovascular risk factors, we found hazard ratios of 1.28 (95% confidence interval [CI], 1.07-1.52), 1.34 (95% CI, 1.10-1.62), and 1.48 (95% CI, 1.36-1.61) for ischemic stroke, myocardial infarction, and all-cause mortality, respectively. For macroalbuminuria, the hazard ratios were 1.81 (95% CI, 1.46-2.23), 1.99 (95% CI, 1.59-2.48), and 1.83 (95% CI, 1.64-2.04). Similar results were found after adjusting for concomitant medication., Conclusions: This study showed that albuminuria level is associated with higher risk of incident ischemic stroke, myocardial infarction, and all-cause mortality in Type 2 diabetes patients without overt cardiovascular disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose of Review: Excessive supraventricular ectopic activity (ESVEA), in the form of frequent premature atrial contractions (PACs) and runs of PACs, is commonly observed in clinical practice and is frequently considered to be benign. Yet, recent studies have demonstrated a link between ESVEA and adverse cardiovascular outcomes. The aim of this meta-analysis was to examine the association between ESVEA and the risk of atrial fibrillation (AF), stroke, and mortality., Recent Findings: A systematic search was performed in PubMed, EMBASE, and the Cochrane Library up to December 2017 to identify studies assessing adverse cardiovascular outcomes in patients with ESVEA, recorded on ambulatory electrocardiography. ESVEA was defined as a burden of PACs > 30 PACs/h or any runs of ≥20 PACs. The risk estimates for EVSEA and each clinical endpoint were pooled and analyzed separately., Results: Five studies comprising 7545 participants were included in this meta-analysis. The pooled analysis showed that ESVEA doubled the risk of AF (HR 2.19, 95% CI 1.70-2.82). ESVEA was also associated with a higher incidence of stroke (HR 2.23, 95% CI 1.24-4.02). Finally, ESVEA was associated with higher all-cause mortality (HR 1.61, 95% CI 1.25-2.07). Our meta-analysis found that ESVEA is closely associated with AF, stroke, and all-cause mortality. Further studies are required to examine the implication of therapeutic strategies in patients with ESVEA, in order to prevent potential subsequent adverse cardiovascular outcomes.

Background: Previous meta-analyses of randomized controlled trials of oral anticoagulation in patients with heart failure and sinus rhythm reported reduced stroke risk and increased bleeding risk compared to antiplatelets or placebo. However, the effect estimates may be subject to imprecision, as all included trials were prematurely terminated; stroke was not the primary outcome and overall results were primarily driven by a single trial. Recently, new trial data became available., Aim: To provide more accurate estimates of the effect of oral anticoagulation on stroke risk in heart failure patients with sinus rhythm by systematic review and meta-analysis of available randomized controlled trials including recently published evidence., Methods: We searched PubMed and Scopus for full-text articles of randomized controlled trials of oral anticoagulation versus antiplatelet or placebo in heart failure patients with sinus rhythm published between inception and 28 August 2018. The outcomes assessed were any stroke, major bleeding, and death., Results: In five trials (9490 patients; 21,067 patient-years), oral anticoagulation-treated patients had lower stroke risk (odds ratio (OR) 0.60, 95%CI: 0.46-0.78, absolute-risk-reduction: 1.3%, number-needed-to-treat: 77), higher major bleeding risk (OR: 1.92, 95%CI: 1.51-2.45, absolute-risk-increase: 2.0%, number-needed-to-harm: 50), and no significant difference in death rates (OR: 0.90, 95%CI: 0.73-1.11) compared to antiplatelets or placebo., Conclusions: In the largest meta-analysis to date, oral anticoagulation is associated with a considerable reduction of stroke risk, which is offset by a significant increase in major bleeding risk. For every 1000 patients treated with oral anticoagulation rather than antiplatelet or no antithrombotic treatment for 2.21 years, 13 strokes are prevented but 20 additional major hemorrhages occur, without significant difference in death rates.

Background: Atrial fibrillation (AF) is associated with an increased risk of stroke, and the use of oral anticoagulation reduces stroke and all-cause mortality. Geographical differences may exist in AF risk factors, risk stratification and treatment strategies., Methods: A post-hoc subgroup analysis derived from randomized controlled trials, the SPORTIF III and V trials, studying differences between European and North American warfarin-assigned non-valvular AF patients., Results: Of 3359 patients 41.6% (n=1397) were enrolled in Europe and 1962 (58.4%) from North America. CHA 2 DS 2 -VASc (p=0.002) and HAS-BLED (p<0.001) scores were higher in North Americans. Good anticoagulation control was more common in North American patients than Europeans. 1-Kaplan-Meier estimate curves show that North Americans had a lower risk of stroke/systemic embolic event (SEE) (p=0.012), but higher risk of myocardial infarction(MI) (p=0.007) and major bleeding (p<0.001), compared to Europeans. Cox multivariate analysis confirmed a lower stroke/SEE risk (p=0.008) and higher MI (p=0.014) and major bleeding risks (p<0.001) in North Americans., Conclusions: Compared to European AF patients, North Americans had better anticoagulation control and higher thromboembolic and bleeding risk profiles. At follow-up, North American patients had lower stroke/SEE risk but higher MI and major bleeding risks compared to Europeans. Further studies are needed to understand these differences and the discordance between risk profile and lower stroke/SEE rates in North American compared to European patients., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Atrial fibrillation affects 33.5 million people worldwide and its prevalence is expected to double by 2050 because of the aging population. Atrial fibrillation confers a 5-fold higher risk of ischemic stroke compared to sinus rhythm. We present our view of the role of shared medical decision-making to combat global underutilization of oral anticoagulation for stroke prevention in atrial fibrillation patients. Oral anticoagulation underuse is widespread as it is present within atrial fibrillation patients of all risk strata and in countries across all income levels. Reasons for oral anticoagulation underuse include but are probably not limited to poor risk stratification, over-interpretation of contraindications, and discordance between physician prescription preferences and actual administration. By comparing a catastrophic event to the consequences of atrial fibrillation related strokes, it may help physicians and patients understand the negative outcomes associated with oral anticoagulation under-utilization and the magnitude to which oral anticoagulations neutralize atrial fibrillation burden.

Background: Few existing stroke registries allow for evaluation of stroke severity, stroke subtype and antithrombotic usage prior to stroke onset over a given time period. The present study aimed to elucidate temporal trends in initial presenting stroke severity, stroke subtype and prior antithrombotic use over a 12-year period in a Japanese multicenter stroke registry., Methods and results: We included 71,017 acute ischemic stroke patients (72±12 years old; 27,445 women) from the Japan Standard Stroke Registry Study (JSSRS) who were admitted to 94 hospitals between 2001 and 2012. The mean age of stroke onset increased gradually over time (P<0.001). Cardioembolic stroke patients (n=19,247) exhibited more severe NIHSS scores when compared with those with non-cardioembolic stroke (n=50,427). The proportion of cardioembolic stroke patients tended to increase over time, rising from 25.9% in 2001-2002 to 30.2% in 2011-2012 (P<0.001). Among the cardioembolic stroke patients, the frequency of prior anticoagulant use significantly increased from 15.6% in 2001-2002 to 24.8% in 2011-2012 (P<0.001). The frequency of prior antiplatelet use increased from 2001-2002 to 2007-2008 but decreased after 2007-2008. Among both cardioembolic and non-cardioembolic stroke patients, initial stroke severity at admission decreased over time, particularly after 2008., Conclusions: In this Japanese study, the mean age of ischemic stroke onset increased, while the initial neurological severity at presentation decreased, over a 12-year period. (Circ J 2016; 80: 2033-2036).

Introduction: Strategies to prevent stroke recurrences and stroke-related morbidity and mortality are a major concern for healthcare systems worldwide. Antithrombotic therapy is the cornerstone for the secondary prevention of ischemic stroke., Areas Covered: This article is an overview of currently used antithrombotic therapies in the management of ischaemic stroke with special focus on their pharmacokinetic properties and how these properties may influence their clinical utility. This review covers both antiplatelet drugs and antitcoagulants used in the primary and secondary prevention of ischaemic stroke., Expert Opinion: The role of aspirin in the early management of stroke is well established. Furthermore, antiplatelet drugs (aspirin, aspirin/dypiridamol and clopidogrel) are the cornerstone of secondary prevention of ischaemic stroke, while their role in the primary prevention is less well established. There are limited data on the use of novel antiplatelet agents for the management of stroke patients. Anticoagulation has not been associated with clinical benefits when used early in the management of acute ischaemic stroke. Long-term therapy with vitamin K antagonists provides prognostic benefit in patients with atrial fibrillation and additional stroke risk factors. New oral anticoagulants have demonstrated at least similar efficacy with vitamin K anatagonists in preventing stroke in patients with atrial fibrillation.

Current European atrial fibrillation (AF) guidelines have assigned a strong recommendation for the initiation of antithrombotic therapy to prevent thromboembolism in all but those AF patients at low risk (or with contraindications). Furthermore, the selection of antithrombotic therapy is based on the absolute risks of thromboembolism and bleeding, and the relative risk and benefit for a given patient. By their very mechanism of action, antithrombotic agents used for stroke prevention in AF will potentially increase the risk of bleeding events. Moreover, the introduction of novel oral anticoagulation agents have introduced new, hitherto ill-defined, deficiencies in the authors' knowledge with respect to anticoagulation monitoring, availability of direct antidotes, drug-drug interactions and the ability to appropriately control and reverse their actions if bleeding events occur. The authors present a comprehensive review on all aspects of bleeding related to currently licensed antithrombotic agents used for stroke prevention in patients with AF.

Unlabelled: Stroke Risk Stratification. , Introduction: Appropriate stroke risk stratification is essential to ensure suitable tailoring of antithrombotic therapy. The objective of this study was to assess the predictive value of stroke risk classification schemes and to identify patients with atrial fibrillation (AF) who are at substantial risk of stroke despite optimal anticoagulant therapy, in a "real world" consecutive elderly AF cohort., Methods: Six hundred and sixty-two consecutive AF patients (mean [SD] age 74 [7.7] years; 36.1% female) referred to the Anticoagulation Clinic of the Azienda Ospedaliera Careggi of Florence, Italy, were included and followed-up for a mean 3.6 ± 2.7 years for the incidence of thromboembolic (TE) events. The ability of the new CHA(2) DS(2) -VASc schema to predict TE was compared with other contemporary stroke risk schema (including CHADS(2) , NICE 2006, ACC/AHA/ESC 2006, and ACCP 2008), by determining the c-statistic., Results: Univariate predictors of TE events were female gender (odds ratio 1.9; 95%CI [confidence intervals] 1.01-3.70) and previous stroke/transient ischemic attack (TIA)/TE (OR 5.6; 95%CI 2.70-11.45), although after adjustment only previous stroke/TIA/TE was an independent predictor of TE (OR 5.5; 95%CI 2.68-11.31; P = 0.0001). All stroke risk schema had modest discriminating ability, with c-statistics ranging from 0.54 (atrial fibrillation investigators [AFI]) to 0.72 (CHA(2) DS(2) -VASc). The CHADS(2) and CHA(2) DS(2) -VASc schemes having the best c-statistics (0.717 and 0.724, respectively) with significant discriminating value between risk strata (both P < 0.001). The proportion of patients assigned to individual risk categories varied widely across the schema, with those categorized as "moderate-risk" ranging from 5.3% (CHA(2) DS(2) -VASc) to 49.2% (CHADS(2) -classical)., Conclusion: In this "real world" cohort, current published risk schemas have modest predictive ability, with the CHADS(2) and CHA(2) DS(2) -VASc schemes having the best predictive value for thromboembolism. Future trials could assess the value of alternative strategies for thromboprophylaxis in high-risk anticoagulated patients identified by these schemes., (© 2010 Wiley Periodicals, Inc.)

The aims of this article are to review the evidence regarding the use of non-vitamin K oral anticoagulants (NOACs) for secondary stroke prevention as compared to vitamin K antagonists in patients with atrial fibrillation (AF) and in patients with embolic strokes of uncertain source (ESUS), and when to initiate or resume anticoagulation after an ischaemic stroke or intracranial haemorrhage. Four large trials compared NOACs with warfarin in patients with AF. In our meta-analyses, the rate of all stroke or systemic embolism (SE) was 4.94% with NOACs vs. 5.73% with warfarin. Among the patients with AF and previous transient ischaemic attack or ischaemic stroke, the rate of haemorrhagic stroke was halved with a NOAC vs. warfarin, and the rate of major bleeding was 5.7% with a NOAC vs. 6.4% with warfarin. There was no significant difference in mortality. In a trial comparing apixaban with aspirin in patients with AF, the rate of stroke or SE was 2.4% at 1 year with apixaban vs. 9.2% at 1 year with aspirin and the rates of major bleeding were 4.1% with apixaban vs. 2.9% with aspirin. Data from registries confirmed the results from the randomized trials. Initiation or resumption of anticoagulation after ischaemic stroke or cerebral haemorrhage depends on the size and severity of stroke and the risk of recurrent bleeding. Two large trials tested the hypothesis that NOACs are more effective than 100 mg aspirin in patients with ESUS. Neither trial showed a significant benefit of the NOAC over aspirin. In the meta-analysis, the rate all stroke or SE was 4.94% with NOACs vs. 5.73% with warfarin and the rate of haemorrhagic stroke was halved with a NOAC. The four NOACs had broadly similar efficacy for the major outcomes in secondary stroke prevention.

AimsLeft atrium (LA) dilation is associated with adverse cardiovascular (CV) outcomes. Blood stasis, thrombus formation and atrial fibrillation may occur, especially in heart failure (HF) patients. It is not known whether preventive antithrombotic treatment may decrease the incidence of CV events in HF patients with LA enlargement. We investigated the relationship between LA enlargement and CV outcomes in HF patients and the effect of different antithrombotic treatments.Methods and resultsTwo-dimensional echocardiography with LA volume index (LAVi) measurement was performed in 1148 patients with systolic HF from the Warfarin versus Aspirin in Reduced Ejection Fraction (WARCEF) trial. Patients were randomized to warfarin or aspirin and followed for 3.4 ± 1.7 years. While the primary aim of the trial was a composite of ischaemic stroke, death, and intracerebral haemorrhage, the present report focuses on the individual CV events, whose incidence was compared across different LAVi and treatment subgroups. After adjustment for demographics and clinical covariates, moderate or severe LA enlargement was significantly associated with total death (hazard ratio 1.6 and 2.7, respectively), CV death (HR 1.7 and 3.3), and HF hospitalization (HR 2.3 and 2.6) but not myocardial infarction (HR 1.0 and 1.4) or ischaemic stroke (1.1 and 1.5). The increased risk was observed in both patients treated with warfarin or aspirin. In warfarin-treated patients, a time in therapeutic range >60% was associated with lower event rates, and an interaction between LAVi and time in therapeutic range was observed for death (P = 0.034).ConclusionsIn patients with systolic HF, moderate or severe LA enlargement is associated with death and HF hospitalization despite treatment with antithrombotic medications. The possibility that achieving a more consistent therapeutic level of anticoagulation may decrease the risk of death requires further investigation.

BackgroundAlthough high resting heart rate (RHR) is known to be associated with an increased risk of mortality and hospital admission in patients with heart failure, the relationship between RHR and ischemic stroke remains unclear. This study is aimed at investigating the relationship between RHR and ischemic stroke in patients with heart failure in sinus rhythm.MethodsWe examined 2,060 patients with systolic heart failure in sinus rhythm from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. RHR was determined from baseline electrocardiogram, and was examined as both a continuous variable and a categorical variable using quartiles. Ischemic strokes were identified during follow-up and adjudicated by physician review.ResultsDuring 3.5 ± 1.8 years of follow-up, 77 patients (5.3% from Kaplan-Meier [KM] curve) experienced an ischemic stroke. The highest incidence of ischemic stroke (21/503 [KM 6.9%]) was observed in the lowest RHR quartile (RHR 79 beats/min (p = 0.693). Multivariable Cox proportional hazards analysis revealed that RHR was significantly associated with ischemic stroke (hazard ratio per unit decrease: 1.07, 95% CI 1.02-1.13, when RHR

AimsThe aim of this study was to determine whether the CHA2 DS2 -VASc score can predict adverse outcomes such as death, ischaemic stroke, and major haemorrhage, in patients with systolic heart failure in sinus rhythm.Methods and resultsCHA2 DS2 -VASc scores were calculated for 1101 patients randomized to warfarin and 1123 patients randomized to aspirin. Adverse outcomes were defined as death or ischaemic stroke, death alone, ischaemic stroke alone, and major haemorrhage. Using proportional hazards models, we found that each 1-point increase in the CHA2 DS2 -VASc score was associated with increased hazard of death or ischaemic stroke events [hazard ratio (HR) for the warfarin arm = 1.21, 95% confidence interval (CI) 1.13-1.30, P < 0.001; for aspirin, HR = 1.20, 95% CI 1.11-1.29, P < 0.001]. Similar increased hazards for higher CHA2 DS2 -VASc scores were observed for death alone, ischaemic stroke alone, and major haemorrhage. Overall performance of the CHA2 DS2 -VASc score was assessed using c-statistics for full models containing the risk score, treatment assignment, and score-treatment interaction, with the c-statistics for the full models ranging from 0.57 for death to 0.68 for major haemorrhage.ConclusionsThe CHA2 DS2 -VASc score predicted adverse outcomes in patients with systolic heart failure in sinus rhythm, with modest prediction accuracy.

EDOSURE is a trial program of the direct oral anticoagulant drug edoxaban, comprising ten randomized clinical trials of which eight are currently published. They evaluate the use of edoxaban in the treatment of nonvalvular atrial fibrillation and acute venous thromboembolism, including in special circumstances such as patients undergoing cardiac procedures, cancer-associated venous thromboembolism, and elderly patients whose bleeding risk precludes conventional anticoagulation strategies. As a result of the collective evidence generated by EDOSURE, edoxaban is now recommended as a treatment option by numerous international guidelines. This review summarizes the context, rationale, and key findings of the studies. EDOSURE is a collection of clinical trials of the medication edoxaban – a blood thinner used to treat or prevent clotting. It encompasses ten trials, eight of which are complete and two are ongoing. Edoxaban's main uses are in patients with atrial fibrillation, or venous clots (e.g., deep vein thrombosis). Trials of blood thinners need to assess the balance of effectiveness (how well the drug treats or prevents clotting) against risk (causing bleeding). These trials collectively demonstrate first that edoxaban is an effective treatment in these conditions and is at least as safe as traditional options like warfarin. Second, in patients with atrial fibrillation who are undergoing procedures like cardiac stenting or ablations, edoxaban is as effective as the previous standard treatments. Finally, in higher-risk populations, such as frail and/or elderly patients, edoxaban can represent a relatively safe option at lower doses. This article is a review of the individual trials, their important findings, and potential limiting factors. Article highlights EDOSURE is an ongoing clinical trial program of edoxaban – a direct oral anticoagulant. In its entirety, it provides an evidence base for edoxaban use in a variety of clinical scenarios, both for nonvalvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). Engage-TIMI-48 (2013) found edoxaban (at two different doses – 30 and 60 mg OD) noninferior to warfarin for the prevention of stroke in patients with NVAF. Edoxaban was safer with regard to bleeding events. Hokusai-VTE (2013) assessed edoxaban use in acute VTE. Edoxaban was again noninferior for efficacy (prevention of recurrent VTE), and superior in terms of safety (major or clinically relevant nonmajor bleeding). Ensure AF (2016) found that for NVAF patients undergoing direct current cardioversion, both edoxaban and warfarin represent safe anticoagulant strategies, with very low rates of iatrogenic stroke. However, the study was underpowered for the demonstration of noninferiority. ELIMINATE-AF (2019) assessed NVAF patients undergoing catheter ablation, with the primary efficacy outcome Similarly to Ensure-AF, rates of stroke and bleeding were very low in both warfarin and vitamin K antagonist arms, precluding noninferiority calculations. The authors concluded, however, both are viable options in this patient group. ENTRUST-AF-PCI (2019) examined NVAF patients undergoing percutaneous coronary intervention (PCI), comparing dual therapy with edoxaban + P2Y12 inhibitor, versus triple therapy with warfarin + P2Y12 inhibitor + aspirin. The edoxaban regime was noninferior for efficacy (a composite outcome including stent thrombosis alongside major adverse cardiovascular events), and trended toward superiority for safety (major bleeding). ENVISAGE-TAVI AF (2021) investigated edoxaban use after successful transcatheter aortic valve implantation (TAVI) in patients with concomitant AF. The comparator was a vitamin K antagonist (predominantly warfarin). While noninferiority was reached for efficacy, the main finding from this study was a 40% higher risk of bleeding in the edoxaban arm, a potentially surprising contrast to the other trials discussed in this review. One possible explanation for this difference is the older, frailer population undergoing TAVI compared with the other study cohorts. Hokusai VTE-Cancer (2017) challenged the idea that heparin-derived anticoagulants were the gold standard in cancer-associated VTE. In this study, edoxaban, met noninferiority thresholds for efficacy and safety compared with dalteparin and trended toward a lower rate of recurrent VTE. There was, however, a signal for increased gastrointestinal bleeding in patients with gastrointestinal malignancies. ELDERCARE-AF (2020) was an innovative trial of low-dose edoxaban (15 mg OD) in frail elderly patients who were considered too high risk for traditional anticoagulant medications. Compared with placebo, edoxaban was associated with a 66% reduction in stroke or systemic embolism, at the cost of an increased rate of bleeding, though the latter did not reach statistical significance. STABLED and ENRICH-AF are ongoing trials. STABLED is assessing the effect of catheter ablation on stroke risk, in AF patients who are taking edoxaban. ENRICH-AF is investigating edoxaban versus aspirin use in AF patients with recent intracranial hemorrhage and high predicted stroke risk. Together – these trials support the use of edoxaban for NVAF and VTE across a broad range of specific clinical scenarios. Its bleeding risk profile is generally favorable compared with warfarin, except possibly in older frailer patients. [ABSTRACT FROM AUTHOR]

Background and purposeIn heart failure (HF), left ventricular ejection fraction (LVEF) is inversely associated with mortality and cardiovascular outcomes. Its relationship with stroke is controversial, as is the effect of antithrombotic treatment. We studied the relationship of LVEF with stroke and cardiovascular events in patients with HF and the effect of different antithrombotic treatments.MethodsIn the Warfarin Versus Aspirin in Reduced Ejection Fraction (WARCEF) trial, 2305 patients with systolic HF (LVEF≤35%) and sinus rhythm were randomized to warfarin or aspirin and followed for 3.5±1.8 years. Although no differences between treatments were observed on primary outcome (death, stroke, or intracerebral hemorrhage), warfarin decreased the stroke risk. The present report compares the incidence of stroke and cardiovascular events across different LVEF and treatment subgroups.ResultsBaseline LVEF was inversely and linearly associated with primary outcome, mortality and its components (sudden and cardiovascular death), and HF hospitalization, but not myocardial infarction. A relationship with stroke was only observed for LVEF of

We sought to assess the performance of existing bleeding risk scores, such as the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score or the Outpatient Bleeding Risk Index (OBRI), in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell C-statistic and net reclassification improvement index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly greater C-statistic (0.72 vs 0.61; p = 0.03) compared to HAS-BLED, although the net reclassification improvement for comparing OBRI to HAS-BLED was not significant (0.32, 95% confidence interval [CI] -0.18 to 0.37). Performance of the OBRI and HAS-BLED risk scores was similar for the aspirin arm. For participants with OBRI scores of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (hazard ratio [HR] 0.51, 95% CI 0.26 to 0.98, p = 0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66 to 2.30, p = 0.51). For those with OBRI score of ≥2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27 to 1.15, p = 0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99 to 8.22, p

BackgroundThe aim of this study is to examine the relationship between time in the therapeutic range (TTR) and clinical outcomes in heart failure patients in sinus rhythm treated with warfarin.Methods and resultsWe used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death), with death alone, ischemic stroke alone, major hemorrhage alone, and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated patients, with TTR being treated as a time-dependent covariate. A total of 2217 patients were included in the analyses; among whom 1067 were randomized to warfarin and 1150 were randomized to aspirin. The median (interquartile range) follow-up duration was 3.6 (2.0-5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted P

Background and purposeWARCEF randomized 2,305 patients in sinus rhythm with ejection fraction (EF) ≤ 35% to warfarin (INR 2.0-3.5) or aspirin 325 mg. Warfarin reduced the incident ischemic stroke (IIS) hazard rate by 48% over aspirin in a secondary analysis. The IIS rate in heart failure (HF) is too low to warrant routine anticoagulation but epidemiologic studies show that prior stroke increases the stroke risk in HF. In this study, we explore IIS rates in WARCEF patients with and without baseline stroke to look for risk factors for IIS and determine if a subgroup with an IIS rate high enough to give a clinically relevant stroke risk reduction can be identified.MethodsWe compared potential stroke risk factors between patients with baseline stroke and those without using the exact conditional score test for Poisson variables. We looked for risk factors for IIS, by comparing IIS rates between different risk factors. For EF we tried cut-off points of 10, 15 and 20%. The cut-off point 15% was used as it was the highest EF that was associated with a significant increase in IIS rate. IIS and EF strata were balanced as to warfarin/aspirin assignment by the stratified randomized design. A multiple Poisson regression examined the simultaneous effects of all risk factors on IIS rate. IIS rates per hundred patient years (/100 PY) were calculated in patient groups with significant risk factors. Missing values were assigned the modal value.ResultsTwenty of 248 (8.1%) patients with baseline stroke and 64 of 2,048 (3.1%) without had IIS. IIS rate in patients with baseline stroke (2.37/100 PY) was greater than patients without (0.89/100 PY) (rate ratio 2.68, p < 0.001). Fourteen of 219 (6.4%) patients with ejection fraction (EF)

BackgroundThe Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial found no difference in the primary outcome between warfarin and aspirin in 2305 patients with reduced left ventricular ejection fraction in sinus rhythm. However, it is unknown whether any subgroups benefit from warfarin or aspirin.Methods and resultsWe used a Cox model stepwise selection procedure to identify subgroups that may benefit from warfarin or aspirin on the WARCEF primary outcome. A secondary analysis added major hemorrhage to the outcome. The primary efficacy outcome was time to the first to occur of ischemic stroke, intracerebral hemorrhage, or death. Only age group was a significant treatment effect modifier (P for interaction, 0.003). Younger patients benefited from warfarin over aspirin on the primary outcome (4.81 versus 6.76 events per 100 patient-years: hazard ratio, 0.63; 95% confidence interval, 0.48-0.84; P=0.001). In older patients, therapies did not differ (9.91 versus 9.01 events per 100 patient-years: hazard ratio, 1.09; 95% confidence interval, 0.88-1.35; P=0.44). With major hemorrhage added, in younger patients the event rate remained lower for warfarin than aspirin (5.41 versus 7.25 per 100 patient-years: hazard ratio, 0.68; 95% confidence interval, 0.52-0.89; P=0.005), but in older patients it became significantly higher for warfarin (11.80 versus 9.35 per 100 patient-years: hazard ratio, 1.25; 95% confidence interval, 1.02-1.53; P=0.03).ConclusionsIn patients

Background: Suboptimal low dosages of non-vitamin K antagonist oral anticoagulants (NOACs) are often inappropriately used due to a fear of bleeding, particularly among elderly patients. Such practice is common in Asia, and we aimed to evaluate the use of low-dose NOACs and their impact on clinical outcomes among Chinese patients with atrial fibrillation. Methods: The Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry was a prospective, multicenter study conducted in China from October 2014 to December 2018. For this report, we included NOAC-treated patients with available data on NOAC dosage and one-year follow-up. Logistic regression analysis assessed the association (adjusted for age, sex, prior ischemic stroke, prior major bleeding, heart failure, coronary artery disease, hypertension, diabetes mellitus, chronic kidney disease, liver disease, current anemia) between the low doses and study outcomes among NOAC-treated patients, as well as comparisons with non-anticoagulated patients. Results: The eligible cohort included 1310 NOAC-treated patients (mean age of 72.1 ± 10.9; 38.9% female), of whom 341 (26.0%) received a low "off-label" dose. The use of low-dose NOACs was independently associated with higher odds of the composite outcome (OR: 2.51; 95% CI: 1.11–5.71) and thromboembolism (OR: 4.73; 95% CI: 1.11–20.01). Compared with non-anticoagulated patients, lower rates of the composite outcome (7.3% vs. 11.3%; p = 0.025) and all-cause death (5.3% vs. 9.7%; p = 0.007) were seen in the low-dose group (ORs 0.50; 95% CI: 0.32–0.78, and 0.42; 95% CI: 0.26–0.70, respectively). Conclusions: Low doses of NOACs should not be recommended as a part of standard therapy among Chinese patients with atrial fibrillation as their use was associated with a higher odds ratio of the composite outcome and thromboembolic events compared with standard dose NOAC regimens. Compared to non-treatment, the use of low-dose NOAC may result in a survival benefit (but not thromboembolic reduction) among high-risk patients. [ABSTRACT FROM AUTHOR]

Further research is needed to refine risk prediction models for adverse cardiovascular outcomes following stroke in contemporary clinical practice, such as incident atrial fibrillation (AF), recurrent stroke, and cognitive impairment and dementia. The aims of this study are to prospectively investigate cardiovascular outcomes and risk factors for incident cardiovascular disease in a post-stroke cohort, and to externally validate, refine and expand current risk prediction models for cardiovascular and cardiovascular-related outcomes. The study sample size was based on the development of post-stroke risk prediction models for AF and was calculated as 1222 participants. The study design is a multicentre, prospective, observational cohort study. Participants will be adult patients admitted for ischaemic stroke confirmed by stroke physician or transient ischaemic attack (TIA) confirmed by MRI. Routinely collected data will be used in addition to the completion of simple validated questionnaires by the participants. Follow-up will be undertaken 12-months from the date of admission to hospital, in addition to linkage to routinely collected follow-up hospitalisation and mortality data. The primary outcomes are cardiovascular outcomes (including incident AF, stroke, TIA and myocardial infarction) at 12-month follow-up, all-cause mortality and mortality from cardiovascular causes, and incident cognitive impairment and dementia. Secondary outcomes include changes in function, depression, anxiety, fatigue and quality of life. The study has received approval from the Health Research Authority Research Ethics Committee (21/WA/0209), and is registered on https://www.clinicaltrials.gov/ (Identifier NCT05132465). Recruitment for the study began in October 2021 with completion of recruitment at all participating centres anticipated by October 2022. [ABSTRACT FROM AUTHOR]

Abstract Background Atrial fibrillation is a serious public health problem posing a considerable burden to not only patients, but the healthcare environment due to high rates of morbidity, mortality, and medical resource utilization. There are limited data on the variation in treatment practice patterns across different countries, healthcare settings and the associated health outcomes. Methods/design RHYTHM-AF was a prospective observational multinational study of management of recent onset atrial fibrillation patients considered for cardioversion designed to collect data on international treatment patterns and short term outcomes related to cardioversion. We present data collected in 10 countries between May 2010 and June 2011. Enrollment was ongoing in Italy and Brazil at the time of data analysis. Data were collected at the time of atrial fibrillation episode in all countries (Australia, Brazil, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom), and cumulative follow-up data were collected at day 60 (±10) in all but Spain. Information on center characteristics, enrollment data, patient demographics, detail of atrial fibrillation episode, medical history, diagnostic procedures, acute treatment of atrial fibrillation, discharge information and the follow-up data on major events and rehospitalizations up to day 60 were collected. Discussion A total of 3940 patients were enrolled from 175 acute care centers. 70.5% of the centers were either academic (44%) or teaching (26%) hospitals with an overall median capacity of 510 beds. The sites were mostly specialized with anticoagulation clinics (65.9%), heart failure (75.1%) and hypertension clinics (60.1%) available. The RHYTHM-AF registry will provide insight into regional variability of antiarrhythmic and antithrombotic treatment of atrial fibrillation, the appropriateness of such treatments with respect to outcomes, and their cost-efficacy. Observations will help inform strategies to improve cardiovascular outcomes in patients with atrial fibrillation. Trial registration Clinical trials NCT01119716