Reviews Can We Predict Stroke in Atrial Fibrillation?

Stroke prevention with appropriate thromboprophylaxis still remains central to the management of atrial fibrillation (AF). Nonetheless, stroke risk in AF is not homogeneous, but despite stroke risk in AF being a continuum, prior stroke risk stratification schema have been used to 'artificially' categorise patients into low, moderate and high risk stroke strata, so that the patients at highest risk can be identified for warfarin therapy. Data from recent large cohort studies show that by being more inclusive, rather than exclusive, of common stroke risk factors in the assessment of the risk for stroke and thromboembolism in AF patients, we can be so much better in assessing stroke risk, and in optimising thromboprophylaxis with the resultant reduction in stroke and mortality. Thus, there has been a recent paradigm shift towards getting better at identifying the 'truly low risk' patients with AF who do not even need antithrombotic therapy, whilst those with one or more stroke risk factors can be treated with oral anticoagulation, whether as well-controlled warfarin or one or the new oral anticoagulant drugs. The new European guidelines on AF have evolved to deemphasise the artificial low/moderate/high risk strata (as they were not very predictive of thromboembolism, anyway) and stressed a risk factor based approach (within the CHA 2 DS 2 -VASc score) given that stroke risk is a continuum. Those categorised as 'low risk' using the CHA 2 DS 2 -VASc score are 'truly low risk' for thromboembolism, and the CHA 2 DS 2 -VASc score performs as good as-and possibly better--than the CHADS 2 score in predicting those at 'high risk'. Indeed, those patients with a CHA 2 DS 2 -VASc score = 0 are 'truly low risk' so that no antithrombotic therapy is preferred, whilst in those with a CHA 2 DS 2 -VASc score of 1 or more, oral anticoagulation is recommended or preferred. Given that guidelines should be applicable for >80% of the time, for >80% of the patients, this stroke risk assessment approach covers the majority of the patients we commonly seen in everyday clinical practice, and considers the common stroke risk factors seen in these patients. The European guidelines also do stress that antithrombotic therapy is necessary in all patients with AF unless they are age <65 years and truly low risk. Indeed, some patients with 'female gender' only as a single risk factor (but still CHA 2 DS 2 -VASc score of 1, due to gender) do not need anticoagulation, especially if they fulfil the criterion of ''age <65 and lone AF, and very low risk''. In the European and Canadian guidelines, bleeding risk assessment is also emphasised, and the simple validated HAS-BLED score is recommended. A HAS-BLED score of ≥3 represents a sufficiently high risk such that caution and/or regular review of a patient is needed. It also makes the clinician think of correctable common bleeding risk factors, and the availability of such a score allows an informed assessment of bleeding risk in AF patients, when antithrombotic therapy is being initiated

Rationale and study design of a cross sectional study documenting the prevalence of Heart Failure amongst the minority ethnic communities in the UK: the E-ECHOES Study (Ethnic - Echocardiographic Heart of England Screening Study)

Background: Heart failure is an important cause of cardiovascular morbidity and mortality. Studies to date have not established the prevalence heart failure amongst the minority ethnic community in the UK. The aim of the E-ECHOES (Ethnic - Echocardiographic Heart of England Screening Study) is to establish, for the first time, the community prevalence and severity of left ventricular systolic dysfunction (LVSD) and heart failure amongst the South Asian and Black African-Caribbean ethnic groups in the UK.Methods/Design: This is a community based cross-sectional population survey of a sample of South Asian (i.e. those originating from India, Pakistan, Bangladesh) and Black African-Caribbean male and female subjects aged 45 years and over. Data collection undertaken using a standardised protocol comprising a questionnaire incorporating targeted clinical history taking, physical examination, and investigations with resting electrocardiography and echocardiography; and blood sampling with consent. This is the largest study on heart failure amongst these ethnic groups. Full data collection started in September 2006 and will be completed by August 2009.Discussion: The E-ECHOES study will enable the planning and delivery of clinically and cost-effective treatment of this common and debilitating condition within these communities. In addition it will increase knowledge of the aetiology and management of heart failure within minority ethnic communities

Development and Validation of a Predictive Model for Intracranial Haemorrhage in Patients on Direct Oral Anticoagulants

Background Intracranial haemorrhage (ICH) poses a significant threat to patients on Direct Oral Anticoagulants (DOACs), with existing risk scores inadequately predicting ICH risk in these patients. We aim to develop and validate a predictive model for ICH risk in DOAC-treated patients. Methods 24,794 patients treated with a DOAC were identified in a province-wide electronic medical and health data platform in Tianjin, China. The cohort was randomly split into a 4:1 ratio for model development and validation. We utilized forward stepwise selection, Least Absolute Shrinkage and Selection Operator (LASSO), and eXtreme Gradient Boosting (XGBoost) to select predictors. Model performance was compared using the area under the curve (AUC) and net reclassification index (NRI). The optimal model was stratified and compared with the DOAC model. Results The median age is 68.0 years, and 50.4% of participants are male. The XGBoost model, incorporating six independent factors (history of hemorrhagic stroke, peripheral artery disease, venous thromboembolism, hypertension, age, low-density lipoprotein cholesterol levels), demonstrated superior performance in the development dateset. It showed moderate discrimination (AUC: 0.68, 95% CI: 0.64–0.73), outperforming existing DOAC scores (ΔAUC = 0.063, P  = 0.003; NRI = 0.374, P  < 0.001). Risk categories significantly stratified ICH risk (low risk: 0.26%, moderate risk: 0.74%, high risk: 5.51%). Finally, the model demonstrated consistent predictive performance in the internal validation. Conclusion In a real-world Chinese population using DOAC therapy, this study presents a reliable predictive model for ICH risk. The XGBoost model, integrating six key risk factors, offers a valuable tool for individualized risk assessment in the context of oral anticoagulation therapy

Pulse Pressure and Prognosis in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: A high pulse pressure (PP) is associated with adverse cardiovascular (CV) outcomes; however this relationship may be reversed in patients with heart failure with reduced ejection fraction (HFREF). METHODS: Patients from the WARCEF trial with left ventricular ejection fraction \u3c 35% were included. PP was divided into tertiles:54 mm Hg. Age and ejection fraction adjusted Kaplan Meier curves were generated to evaluate the relationship between PP and outcomes [mortality, CV mortality, stroke and HF hospitalizations (HFH)]. Cox proportional hazards models were created incorporating PP as a continuous variable. The interaction of PP with New York Heart Association (NYHA) functional class was examined. Linear and restricted cubic splines were used to study nonlinear association between PP and outcomes. RESULTS: We included 2,299 patients with a mean(+/- SD) follow-up of 3.5 +/- 1.8 years. The lowest tertile of PP (Hg) was associated with significantly higher CV mortality and HFH. Cox proportional hazards models showed a reduction in CV death and HFH with higher PP, with adjusted hazard ratios (HR) of 0.91 (p=0.02) and 0.93 (p=0.04) per 10 mm Hg increase in PP. This relationship was more pronounced in subjects with NYHA functional class III-IV. Spline analysis showed that the association between PP and CV mortality and HFH was only seen at PP values lower than 40-50 mm Hg. CONCLUSIONS: In patients with advanced HFREF, a low PP (Hg) portends a worse prognosis, whereas a high PP (\u3e50 mm Hg) predicts a relatively favorable prognosis. This article is protected by copyright. All rights reserved

Recurrent Stroke in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial.

BACKGROUND AND PURPOSE: WARCEF 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. METHODS: We 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 (/100PY) were calculated in patient groups with significant risk factors. Missing values were assigned the modal value. RESULTS: Twenty 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 (2.37/100PY) was greater than patients without (0.89/100PY) (rate ratio 2.68, p \u3c 0.001). Fourteen of 219 (6.4%) patients with ejection fraction (EF) CONCLUSIONS: In a WARCEF exploratory analysis, prior stroke and E

Quality of Anticoagulation Control in Preventing Adverse Events in Patients with Heart Failure in Sinus Rhythm: Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction Trial Substudy.

BACKGROUND: The 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 RESULTS: We 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 CONCLUSIONS: In patients with heart failure in sinus rhythm, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938

Aspirin Does Not Increase Heart Failure Events in Heart Failure Patients: From the WARCEF Trial.

OBJECTIVES: The aim of this study was to determine whether aspirin increases heart failure (HF) hospitalization or death in patients with HF with reduced ejection fraction receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). BACKGROUND: Because of its cyclooxygenase inhibiting properties, aspirin has been postulated to increase HF events in patients treated with ACE inhibitors or ARBs. However, no large randomized trial has addressed the clinical relevance of this issue. METHODS: We compared aspirin and warfarin for HF events (hospitalization, death, or both) in the 2,305 patients enrolled in the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial (98.6% on ACE inhibitor or ARB treatment), using conventional Cox models for time to first event (489 events). In addition, to examine multiple HF hospitalizations, we used 2 extended Cox models, a conditional model and a total time marginal model, in time to recurrent event analyses (1,078 events). RESULTS: After adjustment for baseline covariates, aspirin- and warfarin-treated patients did not differ in time to first HF event (adjusted hazard ratio: 0.87; 95% confidence interval: 0.72 to 1.04; p = 0.117) or first hospitalization alone (adjusted hazard ratio: 0.88; 95% confidence interval: 0.73 to 1.06; p = 0.168). The extended Cox models also found no significant differences in all HF events or in HF hospitalizations alone after adjustment for covariates. CONCLUSIONS: Among patients with HF with reduced ejection fraction in the WARCEF trial, there was no significant difference in risk of HF events between the aspirin and warfarin-treated patients. (Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction trial [WARCEF]; NCT00041938)

The First Prognostic Model for Stroke and Death in Patients with Systolic Heart Failure

BACKGROUND: Patients with systolic heart failure (HF) are at increased risk of both ischemic stroke and death. Currently, no risk scores are available to identify HF patients at high risk of stroke or death. The Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial studied 2305 HF patients, in sinus rhythm, followed for up to 6 years (3.5±1.5 years). This trial showed no overall difference in those treated with warfarin vs aspirin with regard to death or stroke. The present study develops the first prognostic model to identify patients at higher risk of stroke or death based on their overall risk profile. METHODS AND RESULTS: A scoring algorithm using 8 readily obtainable clinical characteristics as predictors, age, gender, hemoglobin, blood urea nitrogen, ejection fraction, diastolic blood pressure, diabetes status, and prior stroke or transient ischemic attack (C-index=0.65, 95% CI: 0.613-0.681), was developed. It was validated internally using a bootstrap method. In predicting 1-year survival for death alone, our 8-predictor model had an AUC of 0.63 (95% CI: 0.579-0.678) while the 14-predictor Seattle model had an AUC of 0.72. The Seattle model did not report stroke. CONCLUSIONS: This novel prognostic model predicts the overall risk of ischemic stroke or death for HF patients. This model compares favorably for death with the Seattle model and has the added utility of including stroke as an endpoint. Use of this model will help identify those patients in need of more intensive monitoring and therapy and may help identify appropriate populations for trials of new therapies. CLINICAL TRIAL REGISTRATION: http://www.Clinicatrials.govNCT00041938