Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87–0.94), with an additional relative risk for CVD of 0.92 (0.87–0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75–0.93), 0.76 (0.67–0.85), 0.69 (0.59–0.79), or 0.63 (0.52–0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.

Objective: To develop and validate a simple, integer-based score to predict functional outcome in acute ischemic stroke (AIS) using variables readily available after emergency room admission. Methods: Logistic regression was performed in the derivation cohort of previously independent patients with AIS (Acute Stroke Registry and Analysis of Lausanne [ASTRAL]) to identify predictors of unfavorable outcome (3-month modified Rankin Scale score >2). An integer-based point-scoring system for each covariate of the fitted multivariate model was generated by their β-coefficients; the overall score was calculated as the sum of the weighted scores. The model was validated internally using a 2-fold cross-validation technique and externally in 2 independent cohorts (Athens and Vienna Stroke Registries). Results: Age (A), severity of stroke (S) measured by admission NIH Stroke Scale score, stroke onset to admission time (T), range of visual fields (R), acute glucose (A), and level of consciousness (L) were identified as independent predictors of unfavorable outcome in 1,645 patients in ASTRAL. Their β-coefficients were multiplied by 4 and rounded to the closest integer to generate the score. The area under the receiver operating characteristic curve (AUC) of the score in the ASTRAL cohort was 0.850. The score was well calibrated in the derivation (p = 0.43) and validation cohorts (0.22 [Athens, n = 1,659] and 0.49 [Vienna, n = 653]). AUCs were 0.937 (Athens), 0.771 (Vienna), and 0.902 (when pooled). An ASTRAL score of 31 indicates a 50% likelihood of unfavorable outcome. Conclusions: The ASTRAL score is a simple integer-based score to predict functional outcome using 6 readily available items at hospital admission. It performed well in double external validation and may be a useful tool for clinical practice and stroke research.

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4–18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4–18] versus 6 [IQR, 3–14]), P =0.03; (odds ratio, 1.69 [95% CI, 1.08–2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2–6] versus 2 [IQR, 1–4], P <0.001) and death (odds ratio, 4.3 [95% CI, 2.22–8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.

Background and Purpose—: Evidence from the real-world setting complements evidence coming from randomized controlled trials. We aimed to summarize all available evidence from high-quality real-world observational studies about efficacy and safety of nonvitamin-K oral anticoagulants compared with vitamin-K antagonists in patients with atrial fibrillation. Methods—: We searched PubMed and Web of Science until January 7, 2017 for observational nationwide or health insurance databases reporting matched or adjusted results comparing nonvitamin-K oral anticoagulants versus vitamin-K antagonists in patients with atrial fibrillation. Outcomes assessed included ischemic stroke, ischemic stroke or systemic embolism, any stroke or systemic embolism, myocardial infarction, intracranial hemorrhage, major hemorrhage, gastrointestinal hemorrhage, and death. Results—: In 28 included studies of dabigatran, rivaroxaban, and apixaban compared with vitamin-K antagonists, all 3 nonvitamin-K oral anticoagulants were associated with a large reduction of intracranial hemorrhage (apixaban hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.31–0.63; dabigatran HR, 0.42; 95% CI, 0.37–0.49; rivaroxaban HR, 0.64; 95% CI, 0.47–0.86); similar rates of ischemic stroke and ischemic stroke or systemic embolism (apixaban HR, 1.05; 95% CI, 0.75–1.19 and HR, 1.08; 95% CI, 0.95–1.22 / dabigatran HR, 0.96; 95% CI, 0.80–1.16 and HR, 1.17; 95% CI, 0.92–1.50 / rivaroxaban HR, 0.89; 95% CI, 0.76–1.04 and HR, 0.73; 95% CI, 0.52–1.04, respectively); apixaban and dabigatran with lower mortality (HR, 0.65; 95% CI, 0.56–0.75 and HR, 0.63; 95% CI, 0.53–0.75, respectively); apixaban with fewer gastrointestinal (HR, 0.63; 95% CI, 0.42–0.95) and major hemorrhages (HR, 0.55; 95% CI, 0.48–0.63); dabigatran and rivaroxaban with more gastrointestinal hemorrhages (HR, 1.20; 95% CI, 1.06–1.36 and HR, 1.24; 95% CI, 1.08–1.41, respectively); dabigatran and rivaroxaban with similar rate of myocardial infarction (HR, 0.96; 95% CI, 0.77–1.21 and HR, 1.02; 95% CI, 0.54–1.89, respectively). Conclusions—: This meta-analysis confirms the main findings of the randomized controlled trials of dabigatran, rivaroxaban, and apixaban in the real-world setting and, hence, strengthens their validity.