Quality Indicators and Clinical Outcomes of Acute Stroke: Results from a Prospective Multicenter Registry in Greece (SUN4P).

AIM: The Stroke Units Necessity for Patients (SUN4P) project aims to provide essential data on stroke healthcare in Greece. Herein, we present results on established quality indicators and outcomes after first-ever stroke occurrences. METHODS: This prospective multicenter study included consecutive patients admitted to nine hospitals across Greece in 2019-2021. Descriptive statistics were used to present patients' characteristics, key performance measures and stroke outcomes. RESULTS: Among 892 patients, 755 had ischemic stroke (IS) (mean age 75.6 ± 13.6, 48.7% males) and 137 had hemorrhagic stroke (HS) (mean age 75.8 ± 13.2, 57.7% males). Of those, 15.4% of IS and 8% of HS patients were treated in the acute stroke unit (ASU) and 20.7% and 33.8% were admitted to the intensive care unit (ICU) or high-dependency unit (HDU), respectively. A total of 35 (4.6%) out of 125 eligible patients received intravenous alteplase with a door-to needle time of 60 min (21-90). The time to first scan for IS patients was 60 min (31-105) with 53.2% undergoing a CT scan within 60 min post presentation. Furthermore, 94.4% were discharged on antiplatelets, 69.8% on lipid-lowering therapy and 61.6% on antihypertensives. Oral anticoagulants (OAC) were initiated in 73.2% of the 153 IS patients with atrial fibrillation (AF). Among the 687 IS patients who survived, 85.4% were discharged home, 12% were transferred to rehabilitation centers, 1.2% to nursing homes and 1.3% to another hospital. CONCLUSIONS: The SUN4P Registry is the first study to provide data from a prospectively collected cohort of consecutive patients from nine representative national hospitals. It represents an important step in the evaluation and improvement of the quality of acute stroke care in Greece.

Adherence to an integrated care pathway for stroke is associated with lower risk of major cardiovascular events: A report from the Athens Stroke Registry.

BACKGROUND: A recent European Society of Cardiology (ESC) Council on Stroke position paper proposed a holistic integrated care management approach for stroke patients, to improve cardiovascular outcomes. The impact of implementing the ABCstroke pathway 'concept' on clinical outcomes has never been estimated before. In order to investigate the potential effect of ABCstroke pathway adherence to cardiovascular outcomes post stroke, we performed a post-hoc analysis from the Athens Stroke Registry. METHODS AND RESULTS: This analysis was performed in the Athens Stroke Registry, which includes all consecutive patients with acute first-ever ischemic stroke. The Kaplan-Meier product limit was used to estimate the cumulative hazard of each outcome according to adherence with the ABCstroke pathway. We studied 2513 patients [median (IQR) age 71 (62-78) years; 37.7 % female] with ischemic stroke with median follow-up period of 30 (6-75) months. Full adherence to the ABC pathway was identified in 156 (6.2 %) of the patients, while 192 (7.6 %) did not adhere to any of the therapeutic pillars of ABCstroke. Full adherence to ABC treatment pathway was associated with significant reduction of stroke recurrence, compared to patients with no or partial adherence (aHR: 0.61; 95 %CI: 0.37-0.99), as well as a lower risk of MACE (HR: 0.59; 0.39-0.88) and death (aHR: 0.22; 95 %CI: 0.12-0.41). CONCLUSION: Full adherence to the ABCstroke pathway based on the current guidelines was evident in only 6.2 % of our ischaemic stroke cohort but was independently associated with lower risks of stroke recurrence, major cardiovascular events and mortality. This highlights a potential opportunity to improve clinical outcomes post-stroke with a holistic or integrated care management approach.

The Cost and the Value of Stroke Care in Greece: Results from the SUN4P Study.

The aim of this study was to measure the one-year total cost of strokes and to investigate the value of stroke care, defined as cost per QALY. The study population included 892 patients with first-ever acute strokes, hemorrhagic strokes, and ischemic strokes, (ICD-10 codes: I61, I63, and I64) admitted within 48 h of symptoms onset to nine public hospitals located in six cities. We conducted a bottom-up cost analysis from the societal point of view. All cost components including direct medical costs, productivity losses due to morbidity and mortality, and informal care costs were considered. We used an annual time horizon, including all costs for 2021, irrespective of the time of disease onset. The average cost (direct and indirect) was extrapolated in order to estimate the national annual burden associated with stroke. We estimated the total cost of stroke in Greece at EUR 343.1 mil. a year in 2021, (EUR 10,722/patient or EUR 23,308 per QALY). Out of EUR 343.1 mil., 53.3% (EUR 182.9 mil.) consisted of direct healthcare costs, representing 1.1% of current health expenditure in 2021. Overall, productivity losses were calculated at EUR 160.2 mil. The mean productivity losses were estimated to be 116 work days with 55.1 days lost due to premature retirement and absenteeism from work, 18.5 days lost due to mortality, and 42.4 days lost due to informal caregiving by family members. This study highlights the burden of stroke and underlines the need for stakeholders and policymakers to re-organize stroke care and promote interventions that have been proven cost-effective.

Midday Dipping and Circadian Blood Pressure Patterns in Acute Ischemic Stroke.

The purpose of this study was to investigate the alterations in blood pressure (BP) during midday and the changes in circadian BP patterns in the acute phase of ischemic stroke (AIS) with the severity of stroke and their predictive role outcomes within 3 months. A total of 228 AIS patients (a prospective multicenter follow-up study) underwent 24 h ambulatory blood pressure monitoring (ABPM). Mean BP parameters during the day (7:00-22:59), the midday (13:00-16:59), and the night (23:00-6:59), and midday and nocturnal dipping were calculated. Midday SBP dippers had less severe stroke, lower incidence of hypertension and SBP/DBP on admission, lower levels of serum glucose and WBCs, and delayed initiation of ABPM compared to risers. There was a reverse relation between midday SBP dipping and both nocturnal dipping and stroke severity. The "double dippers" (midday and nocturnal dipping) had the least severe stroke, the lowest SBP/DBP on admission, the lowest heart rate from ABPM, and a lower risk of an unfavorable outcome, while the "double risers" had the opposite results, by an approximately five-fold risk of death/disability at 3 months. These findings indicate different circadian BP patterns during the acute phase of AIS, which could be considered a marker of stroke severity and prognosis.

Stroke Patients' Management During COVID-19 Pandemic: Results from the Sun4Patients Web-Based Registry.

Covid-19 pandemic has influenced stroke care in different ways. Recent reports demonstrated a sharp decline in acute stroke admissions worldwide. Even for patients presented to dedicated healthcare services, management at the acute phase may be sub-optimal. On the other hand, Greece has been praised for the early initiation of restriction measures which were associated with a 'milder' surge of SARS-CoV-2 infection. Methods Data derived from a prospective cohort multicenter registry. The study population consisted of first-ever acute stroke patients, hemorrhagic or ischemic, admitted within 48 hours of symptom onset in seven national healthcare system (NHS) and University hospitals in Greece. Two different time periods have been considered, defined as "before Covid-19" (15/12/2019-15/02/2020) and "during Covid-19" (16/02/2020-15/04-2020) era. Statistical comparisons on acute stroke admission characteristics between the two different time periods have been performed. Results This exploratory analysis of 112 consecutive patients showed a reduction of acute stroke admissions by 40during Covid-19 period. No significant differences were observed regarding stroke severity, risk factor profile and baseline characteristics for patients admitted before and during Covid-19 pandemic period. There is a significant delay between symptom onset to CT scan during Covid-19 era compared to the period before pandemic reached Greece (p=0.03). Conclusions The rate of acute stroke admissions has been reduced by 40% during Covid-19 pandemic. Further research is needed to clarify whether the reduction in stroke volume is actual or not and identifying the reasons underlying the paradox.

Sinus rhythm restoration and improved outcomes in patients with acute ischemic stroke and in-hospital paroxysmal atrial fibrillation.

Aims: It is unclear whether early cardiac rhythm control is beneficial in patients with acute ischemic stroke and paroxysmal atrial fibrillation (PAF). We sought to investigate whether PAF self-termination and in-hospital sinus rhythm (SR) restoration is associated with improved outcome in ischemic stroke patients with PAF, compared to those with sustained atrial fibrillation (AF). Methods: Consecutive patients with first-ever acute stroke and confirmed PAF during hospitalization were followed for up to 10 years after the index stroke or until death. We investigated the association of in-hospital self-terminated PAF and PAF conversion to SR compared to sustained AF with 10-year all-cause mortality, stroke recurrence, and major adverse cardiovascular events (MACE). Cox regression analysis was performed to identify independent predictors of each outcome. Results: Among 297 ischemic stroke patients with in-hospital PAF detection, PAF was self-terminated in 87 (29.3%) patients, while 143 (48.1%) patients received antiarrhythmic medication in order to achieve PAF conversion to SR. During a median (Interquartile range, IQR) period of 28 (4-68) months, among patients with self-terminated PAF there were 13.5 deaths, 3.6 stroke recurrences, and 5.3 MACE per 100 patient-year while in patients who underwent medical PAF conversion there were 11.7 deaths, 4.6 stroke recurrences, and 5.8 MACE per 100 patient-year. Patients with sustained AF experienced 23.8 deaths, 8.7 stroke recurrences, and 13.9 MACE per 100 patient-years. In multivariable analysis, compared to patients with sustained AF, PAF self-termination was associated with significantly lower 10 years-risk of death (adjusted hazards ratio (adjHR): HR: 0.63, 95% Confidence interval: 0.40-0.96), stroke recurrence (adjHR: HR: 0.41, 95% CI: 0.19-0.91), and MACE (adjHR: 0.43, 95% CI: 0.23-0.81), while PAF medical conversion to SR was associated with lower 10 years-risk of death (adjHR: 0.65, 95% CI: 0.44-0.97) and MACE (adjHR: 0.56, 95% CI: 0.33-0.95). Discussion: This study showed that in-hospital PAF self-termination was associated with lower risk of 10-year mortality, stroke recurrence, and MACE, potentially attributed to the lower burden of AF, whereas in-hospital PAF conversion to SR was associated with lower risk of 10-year mortality and MACE. Conclusion: Early restoration of sinus rhythm is associated with improved survival and MACE in patients with acute ischemic stroke and PAF.

Prediction of long-term outcomes by arterial stiffness and pressure wave reflections in patients with acute stroke: the Athens Stroke Registry.

BACKGROUND AND PURPOSE: Stroke patients' management might be improved by addressing the role of aortic stiffness (carotid-femoral pulse wave velocity: cfPWV) and pressure wave reflections (PWRs, augmentation index: AIx) in their pathogenesis and outcome. We tested the hypothesis that cfPWV and AIx, separately and combined, predict long-term outcomes [all-cause mortality, incidence of cardiovascular events, stroke recurrence and disability defined by modified Ranking Scale (mRS) ≥3] in patients with acute stroke, using data from the 'Athens Stroke Registry'. METHODS: Data from 552 patients (70% men, age: 66.1 ±â€Š10.4 years, 13.4% deaths from any cause, 21.2% cardiovascular events, 14.1% stroke recurrences and 20.1% poor mRS, mean follow-up 68.4 ±â€Š41.4 months) were analyzed. RESULTS: The main findings were that: high aortic stiffness (cfPWV > 13 m/s) alone is an independent predictor of all-cause mortality and cardiovascular (CV) events, but not of stroke recurrence and poor functional outcome; evaluated separately from aortic stiffness, neither low nor high PWRs have any prognostic value; even after multiple adjustments, patients with both high aortic stiffness (cfPWV > 13 m/s) and low PWRs (Aix < 22%) have almost two-fold higher hazard ratio, not only for all-cause mortality and CV events but also for stroke recurrence and poor functional outcome. CONCLUSIONS: The present study provides evidence about the role of aortic stiffness, PWRs and their combined incremental value in the long-term survival, morbidity, and functional disability after acute stroke.

Moving from traditional to more advanced treatments in stroke care is cost-effective: A case study from Greece.

OBJECTIVES: Stroke is the most common cause of disability in high-income countries. Several countries offer a limited range of advanced treatments with implications for outcomes, disability and costs. This study estimates the burden of disability that could have been avoided through the transition from traditional (no intravenous thrombolytic therapy (IVT), or endovascular thrombectomy (EVT)) to modern stroke treatments (treatment in stroke units, IVT and EVT). We perform a cost-effectiveness analysis comparing best practice with traditional stroke care, using Greece as a case study. MATERIALS AND METHODS: A Markov model was used to calculate costs and Quality Adjusted Life Years (QALYs) for each treatment strategy, using a lifetime horizon. Data for model inputs were derived from meta-analyses of trials, and national and international cost databases. Sensitivity analyses were also performed to address potential uncertainty and test the robustness of the findings. RESULTS: Incremental effectiveness comprised 0.22 QALYs per patient and year. Best practice was cost-effective for more than 90% of all iterations (ICER for the baseline scenario: €2,109.25/QALY). Sensitivity analysis demonstrated that the findings remain robust. Considering the stroke incidence in Greece, the annual additional cost to implement best practice was calculated to be between 0.07%-0.15% of the total health expenditure. CONCLUSION: Best practice stroke treatment was cost-effective and affordable in a case study based on Greece. The results could be leveraged by including effects of preventive policies and rehabilitation. They also highlight the importance of adopting modern treatment strategies from a cost-effectiveness perspective, apart from the improved clinical outcomes.

Estimation of the economic burden of atrial fibrillation-related stroke in Greece.

BACKGROUND: Stroke is aleading cause of death and disability, with atrial fibrillation (AF) being among key risk factors and AF-related stroke inflicting significant burden on healthcare systems and society. The present study was undertaken for estimating the total annual socioeconomic burden of AF-related stroke in Greece and identifying the key cost contributors. RESEARCH DESIGN AND METHODS: A cost-of-illness model was developed for estimating the total annual economic burden of AF-related stroke in Greece, from asocietal perspective (year 2018). Atargeted literature review and an advisory board consisting of key experts in the management of AF and AF-related stroke were performed for collecting local resource use and epidemiological data. RESULTS: The total annual socioeconomic burden of AF-related stroke was estimated at €175million, in 2018. Direct and indirect costs accounted for 59% and 41%, respectively. Main contributors were informal care (21.1%), patients' productivity losses (19.7%) and hospitalizations (15.0%), accounting for more than half of the total costs of AF-related stroke events.Conclusion: A F-related stroke imposes asignificant socioeconomic burden in Greece. Despite results relying on estimations, it seems that ensuring efficient reallocation of resources in appropriate prevention and early intervention strategies could decrease AF-related stroke's burden but also enhance healthcare systems' efficiency. ABBREVIATIONS: AF=atrial fibrillation.

Temporal trends in stroke incidence and case-fatality rates in Arcadia, Greece: A sequential, prospective, population-based study.

BACKGROUND: Stroke incidence and case-fatality are reported to decline in high-income countries during the last decades. Epidemiological studies are important for health services to organize prevention and treatment strategies. AIMS: The aim of this population-based study was to determine temporal trends of stroke incidence and case-fatality rates of first-ever stroke in Arcadia, a prefecture in southern Greece. METHODS: All first-ever stroke cases in the Arcadia prefecture were ascertained using the same standard criteria and multiple overlapping sources in three study periods: from November 1993 to October 1995; 2004; and 2015-2016. Crude and age-adjusted to European population incidence rates were compared using Poisson regression. Twenty-eight days case fatality rates were estimated and compared using the same method. RESULTS: In total, 1315 patients with first-ever stroke were identified. The age-standardized incidence to the European population was 252 per 100,000 person-years (95% CI 231-239) in 1993/1995, 252 (95% CI 223-286) in 2004, and 211 (192-232) in 2015/2016. The overall age- and sex-adjusted incidence rates fell by 16% (incidence rates ratio 0.84, 95% CI: 0.72-0.97). Similarly, 28-day case-fatality rate decreased by 28% (case fatality rate ratio = 0.72, 95% CI: 0.58-0.90). CONCLUSIONS: This population-based study reports a significant decline in stroke incidence and mortality rates in southern Greece between 1993 and 2016.

Case-Fatality and Functional Outcome after Subarachnoid Hemorrhage (SAH) in INternational STRoke oUtComes sTudy (INSTRUCT).

BACKGROUND: There are few large population-based studies of outcomes after subarachnoid hemorrhage (SAH) than other stroke types. METHODS: We pooled data from 13 population-based stroke incidence studies (10 studies from the INternational STRroke oUtComes sTudy (INSTRUCT) and 3 new studies; N=657). Primary outcomes were case-fatality and functional outcome (modified Rankin scale score 3-5 [poor] vs. 0-2 [good]). Harmonized patient-level factors included age, sex, health behaviours (e.g. current smoking at baseline), comorbidities (e.g.history of hypertension), baseline stroke severity (e.g. NIHSS >7) and year of stroke. We estimated predictors of case-fatality and functional outcome using Poisson regression and generalized estimating equations using log-binomial models respectively at multiple timepoints. RESULTS: Case-fatality rate was 33% at 1 month, 43% at 1 year, and 47% at 5 years. Poor functional outcome was present in 27% of survivors at 1 month and 15% at 1 year. In multivariable analysis, predictors of death at 1-month were age (per decade increase MRR 1.14 [1.07-1.22]) and SAH severity (MRR 1.87 [1.50-2.33]); at 1 year were age (MRR 1.53 [1.34-1.56]), current smoking (MRR 1.82 [1.20-2.72]) and SAH severity (MRR 3.00 [2.06-4.33]) and; at 5 years were age (MRR 1.63 [1.45-1.84]), current smoking (MRR 2.29 [1.54-3.46]) and severity of SAH (MRR 2.10 [1.44-3.05]). Predictors of poor functional outcome at 1 month were age (per decade increase RR 1.32 [1.11-1.56]) and SAH severity (RR 1.85 [1.06-3.23]), and SAH severity (RR 7.09 [3.17-15.85]) at 1 year. CONCLUSION: Although age is a non-modifiable risk factor for poor outcomes after SAH, however, severity of SAH and smoking are potential targets to improve the outcomes.

Machine-Learning-Derived Model for the Stratification of Cardiovascular risk in Patients with Ischemic Stroke.

Background Stratification of cardiovascular risk in patients with ischemic stroke is important as it may inform management strategies. We aimed to develop a machine-learning-derived prognostic model for the prediction of cardiovascular risk in ischemic stroke patients. MATERIALS AND METHODS: Two prospective stroke registries with consecutive acute ischemic stroke patients were used as training/validation and test datasets. The outcome assessed was major adverse cardiovascular event, defined as non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death during 2-year follow-up. The variables selection was performed with the LASSO technique. The algorithms XGBoost (Extreme Gradient Boosting), Random Forest and Support Vector Machines were selected according to their performance. The evaluation of the classifier was performed by bootstrapping the dataset 1000 times and performing cross-validation by splitting in 60% for the training samples and 40% for the validation samples. RESULTS: The model included age, gender, atrial fibrillation, heart failure, peripheral artery disease, arterial hypertension, statin treatment before stroke onset, prior anticoagulant treatment (in case of atrial fibrillation), creatinine, cervical artery stenosis, anticoagulant treatment at discharge (in case of atrial fibrillation), and statin treatment at discharge. The best accuracy was measured by the XGBoost classifier. In the validation dataset, the area under the curve was 0.648 (95%CI:0.619-0.675) and the balanced accuracy was 0.58 ± 0.14. In the test dataset, the corresponding values were 0.59 and 0.576. CONCLUSIONS: We propose an externally validated machine-learning-derived model which includes readily available parameters and can be used for the estimation of cardiovascular risk in ischemic stroke patients.

Statin treatment and outcomes after embolic stroke of undetermined source.

The association of low-density lipoprotein cholesterol lowering with outcomes in embolic stroke of undetermined source (ESUS) patients is unclear. In these patients we aimed to assess the effect of statin on stroke recurrence, major adverse cardiovascular events (MACE) and death rates. Consecutive ESUS patients in the Athens Stroke Registry were prospectively followed-up to 10 years for stroke recurrence, MACE, and death. The Nelson-Aalen estimator was used to estimate the cumulative probability by statin allocation at discharge and cox-regression analyses to investigate whether statin at discharge was a predictor of outcomes. Among 264 ESUS patients who were discharged and followed for 4 years, 89 (33.7%) were treated with statin at discharge. Patients who were discharged on statin had lower rates of stroke recurrence (3.58 vs. 7.23/100 patient-years, HR: 0.48; 95% CI 0.26-0.90), MACE (4.98 vs. 9.89/100 patient-years, HR: 0.49; 95% CI 0.29-0.85), and death (3.93 vs. 8.21/100 patient-years, HR: 0.50; 95% CI: 0.28-0.89). In the multivariate analysis, statin treatment at discharge was an independent predictor of stroke recurrence (adjusted HR: 0.48; 95% CI 0.26-0.91), MACE (adjusted HR: 0.48; 95% CI 0.28-0.82), and death (adjusted HR: 0.50; 95% CI 0.27-0.93). Patients with ESUS discharged on statins have lower rates of stroke recurrence, MACE, and death compared to those not receiving statin therapy.

Atrial Cardiopathy and Likely Pathogenic Patent Foramen Ovale in Embolic Stroke of Undetermined Source.

BACKGROUND: Atrial cardiopathy and likely pathogenic patent foramen ovale (PFO) are two potential embolic sources in patients with embolic stroke of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. METHODS: Atrial cardiopathy was defined as increased left atrial diameter index (> 23 mm/m2) or left atrial volume index (> 34 mL/m2), or PR prolongation (≥ 200 ms), or presence of supraventricular extrasystoles in the electrocardiograms performed during hospitalization for the index stoke. The presence of PFO was assessed by transthoracic echocardiography with microbubble test or by transesophageal echocardiography. The presence of PFO was considered as likely pathogenic if the Risk of Paradoxical Embolism score was 7 to 10. RESULTS: Among 367 ESUS patients with available information about the presence of PFO and the presence of atrial cardiopathy (median age: 61 years, 40.6% women), likely pathogenic PFO was diagnosed in 62 (16.9%) and atrial cardiopathy in 122 (33.2%). Only 4 patients (1.1%) had both likely pathogenic PFO and atrial cardiopathy. The prevalence of atrial cardiopathy was lower in patients with likely pathogenic PFO (6.5%) compared with patients with likely incidental PFO (31.2%) or without PFO (40.6%) (Pearson's chi-square test: 26.08, p < 0.001; adjusted odds ratio [OR]: 0.28, 95% confidence interval [CI]: 0.09-0.86). The prevalence of likely pathogenic PFO was lower in patients with atrial cardiopathy compared with patients without atrial cardiopathy (3.3% vs. 23.7%, respectively [Pearson's chi-square test: 24.13, p < 0.001; adjusted OR: 0.2, 95% CI: 0.02-0.6]). CONCLUSION: The presence of atrial cardiopathy is inversely related to the presence of likely pathogenic PFO in patients with ESUS.

Identification of patients with embolic stroke of undetermined source and low risk of new incident atrial fibrillation: The AF-ESUS score.

BACKGROUND AND AIMS: Only a minority of patients with Embolic Stroke of Undetermined Source (ESUS) receive prolonged cardiac monitoring despite current recommendations. The identification of ESUS patients who have low probability of new diagnosis of atrial fibrillation (AF) could potentially support a strategy of more individualized allocation of available resources and hence, increase their diagnostic yield. We aimed to develop a tool that can identify ESUS patients who have low probability of new incident AF. METHODS: We performed multivariate stepwise regression in a pooled dataset of consecutive ESUS patients from three prospective stroke registries to identify predictors of new incident AF. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integer-based point scoring system. RESULTS: Among 839 patients (43.1% women, median age 67.0 years) followed-up for a median of 24.3 months (2999 patient-years), 125 (14.9%) had new incident AF. The proposed score assigns 3 points for age ≥ 60 years; 2 points for hypertension; -1 point for left ventricular hypertrophy reported at echocardiography; 2 points for left atrial diameter >40 mm; -3 points for left ventricular ejection fraction <35%; 1 point for the presence of any supraventricular extrasystole recorded during all available 12-lead standard electrocardiograms performed during hospitalization for the ESUS; -2 points for subcortical infarct; -3 points for the presence of non-stenotic carotid plaques. The rate of new incident AF during follow-up was 1.97% among the 42.3% of the cohort who had a score of ≤0, compared to 26.9% in patients with > 0 (relative risk: 13.7, 95%CI: 5.9--31.5). The area under the curve of the score was 84.8% (95%CI: 79.9--86.9%). The sensitivity and negative predictive value of a score of ≤0 for new incident AF during follow-up were 94.9% (95%CI: 89.3--98.1%) and 98.0% (95%CI: 95.8--99.3%), respectively. CONCLUSIONS: The proposed AF-ESUS score has high sensitivity and high negative predictive value to identify ESUS patients who have low probability of new incident AF. Patients with a score of 1 or more may be better candidates for prolonged automated cardiac monitoring. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ Unique identifier: NCT02766205.

Carotid Atherosclerosis and Patent Foramen Ovale in Embolic Stroke of Undetermined Source.

BACKGROUND: Carotid atherosclerosis and likely pathogenic patent foramen ovale (PFO) are two potential embolic sources in patients with embolic stroke of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. AIM: To investigate the relation between carotid atherosclerosis and likely pathogenic PFO in patients with ESUS. We hypothesized that ipsilateral carotid atherosclerotic plaques are less prevalent in ESUS with likely pathogenic PFO compared to patients with likely incidental PFO or without PFO. METHODS: The presence of PFO was assessed with transthoracic echocardiography with microbubble test and, when deemed necessary, through trans-oesophageal echocardiography. The presence of PFO was considered as likely incidental if the RoPE (Risk of Paradoxical Embolism) score was 0-6 and likely pathogenic if 7-10. RESULTS: Among 374 ESUS patients (median age: 61years, 40.4% women), there were 63 (49.6%) with likely incidental PFO, 64 (50.4%) with likely pathogenic PFO and 165 (44.1%) with ipsilateral carotid atherosclerosis. The prevalence of ipsilateral carotid atherosclerosis was lower in patients with likely pathogenic PFO (7.8%) compared to patients with likely incidental PFO (46.0%) or patients without PFO (53.0%) (p<0.001). After adjustment for multiple confounders, the prevalence of ipsilateral carotid atherosclerosis remained lower in patients with likely pathogenic PFO compared to patients with likely incidental PFO or without PFO (adjusted OR=0.32, 95%CI:0.104-0.994, p=0.049). CONCLUSIONS: The presence of carotid atherosclerosis is inversely related to the presence of likely pathogenic PFO in patients with ESUS.

Recommendations for lipid modification in patients with ischemic stroke or transient ischemic attack: A clinical guide by the Hellenic Stroke Organization and the Hellenic Atherosclerosis Society.

This document presents the consensus recommendations of the Hellenic Stroke Organization and the Hellenic Atherosclerosis Society for lipid modification in patients with ischemic stroke or transient ischemic attack. This clinical guide summarizes the current literature on lipid management and can be of assistance to the physicians treating stroke patients in clinical practice.

Antithrombotic treatment in patients with stroke and supracardiac atherosclerosis.

OBJECTIVE: To compare the efficacy and safety of oral anticoagulants vs antiplatelets in patients with stroke and atherosclerotic plaques in the aortic arch or cervical or intracranial arteries, collectively described as supracardiac atherosclerosis. METHODS: We searched PubMed and Scopus until August 28, 2019, for randomized trials comparing oral anticoagulants vs antiplatelets in patients with stroke and supracardiac atherosclerosis using the terms "anticoagulant or anticoagulation" and "antiplatelet or aspirin" and "randomized controlled trial or RCT" and "stroke or cerebral ischemia" and "aortic or carotid or vertebrobasilar or intracranial or atherosclerosis or stenosis or arterial." Four outcomes were assessed: recurrent ischemic stroke, major ischemic event or death, major bleeding, and intracranial bleeding. Treatment effects (relative risk [RR] and 95% confidence interval [CI]) were estimated by meta-analysis using random-effects models. RESULTS: Among 1,117 articles identified in the literature search, results from 10 randomized controlled trials involving 6,068 patients with stroke/TIA with supracardiac atherosclerosis were included in the meta-analysis. Recurrent ischemic stroke rates were 2.94 per 100 patient-years in the anticoagulant-assigned patients vs 3.30 per 100 patient-years in the antiplatelet-assigned patients (RR, 0.91; 95% CI, 0.70-1.18 for the SJ estimator, I2 = 26%). Major ischemic event or death rates were 4.39 per 100 patient-years in anticoagulant-assigned patients vs 4.32 in antiplatelet-assigned patients (RR, 1.03; 95% CI, 0.79-1.35; I2 = 54.5%). Major bleeding rates were 2.88 per 100 patient-years in anticoagulant-assigned patients vs 0.82 in antiplatelet-assigned patients (RR, 3.21; 95% CI, 1.96-5.24; I2 = 46%). CONCLUSION: This systematic review and meta-analysis showed that anticoagulant-assigned patients with stroke and supracardiac atherosclerosis were not at different risk of ischemic stroke recurrence and increased risk of major bleeding compared to antiplatelet-assigned patients.

Bleeding risk comparison between direct oral anticoagulants at doses approved for atrial fibrillation and aspirin: systematic review, meta-analysis and meta-regression.

BACKGROUND: A considerable proportion of patients with atrial fibrillation (AF) are still treated with aspirin despite current guidelines due to presumed favorable safety. AIM: We performed a systematic review and meta-analysis of bleeding outcomes in randomized controlled trials (RCTs) comparing direct oral anticoagulants (DOACs) at doses approved for AF vs. aspirin. METHODS: We searched PubMed and Scopus for phase-III RCTs of DOACs at AF-approved doses vs. aspirin. Outcomes assessed were major-, intracranial-, gastrointestinal-, clinically-relevant-non-major- and fatal bleeding. We performed two subgroup analyses: one per patient population i.e. those at high risk of arterial or venous thromboembolism, and one per DOAC. We also performed a meta-regression to assess the association with patient age. RESULTS: In 4 eligible trials (20,440 patients) comparing DOACs vs. aspirin, the ORs were: 1.52 (95%CI: 0.91-2.53) for major bleeding in patients at high risk of arterial thromboembolism and 1.55 (95%CI:0.99-2.45, relative-risk-increase:55%, absolute-risk-increase:0.6%, number-needed-to-harm:170) in the overall analysis; 1.39 (95%CI:0.62-3.14) for intracranial bleeding in patients at high risk of arterial thromboembolism which was similar for the overall analysis; 1.27 (95%CI: 0.84-1.92) for gastrointestinal bleeding in patients at high risk of arterial thromboembolism and 1.26 (95%CI:0.86-1.85) in the overall analysis. Patient age was not a predictor of the magnitude of ORs for all bleeding outcomes. CONCLUSION: The present meta-analysis does not support the use of aspirin over DOACs in AF. Accordingly, the level of evidence of the related recommendations should be upgraded, which in turn may reduce further the proportion of AF patients treated with antiplatelets.