Cerebral venous sinus thrombosis associated with cancer: analysis of the ACTION-CVT study.

Nearly one fifth of patients with venous thromboembolism (VTE) have cancer. When both of these conditions occur, especially in cases of cerebral vein thrombosis (CVT), patient management is often challenging. The aim of this study was to compare the characteristics and event courses in patients affected by CVT with and without cancer. Consecutive patients with CVT from the ACTION-CVT cohort study were included if cancer status was reported. Risk factors as well as the clinical and radiological characteristics of patients were compared. Univariable and multivariable analyses were performed to assess variables associated with cancer. Kaplan-Meier method and log-rank test, logistic regression analysis, and propensity score matching were used to investigate any association between cancer-related CVT and study outcomes (primary outcome at 3-months: recurrent VTE or major hemorrhage; recurrent VTE; major hemorrhage; recanalization status; all-cause-death). Overall, 1,023 patients with CVT were included, of which 6.5% had cancer. Older age (adjusted odds ratio [aOR] 1.28 per decade increase; 95% confidence interval [CI] 1.08-1.52) and absence of headache (aOR 0.47; 95% CI 0.27-0.84) were independently associated with cancer. Patients with cancer had a higher risk of recurrent VTE or major hemorrhage (aOR 3.87; 95% CI 2.09-7.16), all-cause-death (aOR 7.56 95% CI 3.24-17.64), and major hemorrhage (aOR 3.70 95% CI 1.76-7.80). Recanalization rates, partial or complete, was not significantly different. CVT patients with cancer were more likely to be older, have no referred headache, and have worse outcomes compared to CVT patients without cancer.

Early Versus Late Initiation of Direct Oral Anticoagulants After Ischemic Stroke in People With Atrial Fibrillation and Hemorrhagic Transformation: Prespecified Subanalysis of the Randomized-controlled ELAN Trial.

BACKGROUND: Whether hemorrhagic transformation (HT) modifies the treatment effect of early versus late initiation of direct oral anticoagulation (DOAC) in people with ischemic stroke and atrial fibrillation is unknown. METHODS: This is a post-hoc analysis of the ELAN trial. The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage (sICH), major extracranial bleeding, systemic embolism, or vascular death within 30 days. Secondary outcomes were the individual components, 30- and 90-day functional outcome. We estimated outcomes based on HT, subclassified as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) on pre-randomization imaging (core-lab rating) using adjusted risk differences (aRD) between treatment arms. RESULTS: Overall, 247/1970 (12.5%) participants had HT (114 HI 1, 77 HI 2, 34 PH 1, 22 PH 2). For the primary outcome, the estimated aRD (early versus late) was -2.2% (-7.8 to 3.5%) in people with HT (HI: -4.7%, -10.8 to 1.4%; PH: 6.1%, -8.4 to 20.7%), and -0.9% (-2.6 to 0.8%) in people without. Numbers of sICH were identical in people with and without HT. With early treatment, the estimated aRD for poor 90-day functional outcome (mRS 3-6) was 11.4% (-0.9 to 23.7%) in participants with HT (HI: 7.2%, -6.6 to 21.0%; PH: 25.1%, 0.2 to 50.0%), and -2.6% (-7.1 to 1.8%) in people without HT. CONCLUSIONS: We found no evidence of major treatment effect heterogeneity or safety concerns with early versus late DOAC initiation in people with and without HT. However, early DOAC initiation may worsen functional outcomes in people with PH.

Early vs Late Anticoagulation in Minor, Moderate, and Major Ischemic Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial.

Importance: Whether infarct size modifies the treatment effect of early vs late direct oral anticoagulant (DOAC) initiation in people with ischemic stroke and atrial fibrillation is unknown. Objective: To assess whether infarct size modifies the safety and efficacy of early vs late DOAC initiation. Design, Setting, and Participants: Post hoc analysis of participants from the multinational (>100 sites in 15 countries) randomized clinical Early Versus Later Anticoagulation for Stroke With Atrial Fibrillation (ELAN) trial who had (1) acute ischemic stroke, (2) atrial fibrillation, and (3) brain imaging available before randomization. The ELAN trial was conducted between October 2017 and December 2022. Data were analyzed from October to December 2023 for this post hoc analysis. Intervention: Early vs late DOAC initiation after ischemic stroke. Early DOAC initiation was within 48 hours for minor or moderate stroke or on days 6 to 7 for major stroke; late DOAC initiation was on days 3 to 4 for minor stroke, days 6 to 7 for moderate stroke, and days 12 to 14 for major stroke. Main Outcomes and Measures: The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, extracranial bleeding, systemic embolism, or vascular death within 30 days. The outcome was assessed according to infarct size (minor, moderate, or major) using odds ratios and risk differences between treatment arms. Interrater reliability for infarct size between the core laboratory and local raters was assessed, and whether this modified the estimated treatment effects was also examined. Results: A total of 1962 of the original 2013 participants (909 [46.3%] female; median [IQR] age, 77 [70-84] years) were included. The primary outcome occurred in 10 of 371 participants (2.7%) with early DOAC initiation vs 11 of 364 (3.0%) with late DOAC initiation among those with minor stroke (odds ratio [OR], 0.89; 95% CI, 0.38-2.10); in 11 of 388 (2.8%) with early DOAC initiation vs 14 of 392 (3.6%) with late DOAC initiation among those with moderate stroke (OR, 0.80; 95% CI, 0.35-1.74); and in 8 of 219 (3.7%) with early DOAC initiation vs 16 of 228 (7.0%) with late DOAC initiation among those with major stroke (OR, 0.52; 95% CI, 0.21-1.18). The 95% CI for the estimated risk difference of the primary outcome in early anticoagulation was -2.78% to 2.12% for minor stroke, -3.23% to 1.76% for moderate stroke, and -7.49% to 0.81% for major stroke. There was no significant treatment interaction for the primary outcome. For infarct size, interrater reliability was moderate (κ = 0.675; 95% CI, 0.647-0.702) for local vs core laboratory raters and strong (κ = 0.875; 95% CI, 0.855-0.894) between core laboratory raters. Conclusions and Relevance: The treatment effect of early DOAC initiation did not differ in people with minor, moderate, or major stroke assessed by brain imaging. Early treatment was not associated with a higher rate of adverse events, especially symptomatic intracranial hemorrhage, for any infarct size, including major stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03148457.

Timing of oral anticoagulants initiation for atrial fibrillation after acute ischemic stroke: A systematic review and meta-analysis.

INTRODUCTION: There is a longstanding clinical uncertainty regarding the optimal timing of initiating oral anticoagulants (OAC) for non-valvular atrial fibrillation following acute ischemic stroke. Current international recommendations are based on expert opinions, while significant diversity among clinicians is noted in everyday practice. METHODS: We conducted an updated systematic review and meta-analysis including all available randomized-controlled clinical trials (RCTs) and observational cohort studies that investigated early versus later OAC-initiation for atrial fibrillation after acute ischemic stroke. The primary outcome was defined as the composite of ischemic and hemorrhagic events and mortality at follow-up. Secondary outcomes included the components of the composite outcome (ischemic stroke recurrence, intracranial hemorrhage, major bleeding, and all-cause mortality). Pooled estimates were calculated with random-effects model. RESULTS: Nine studies (two RCTs and seven observational) were included comprising a total of 4946 patients with early OAC-initiation versus 4573 patients with later OAC-initiation following acute ischemic stroke. Early OAC-initiation was associated with reduced risk of the composite outcome (RR = 0.74; 95% CI:0.56-0.98; I2 = 46%) and ischemic stroke recurrence (RR = 0.64; 95% CI:0.43-0.95; I2 = 60%) compared to late OAC-initiation. Regarding safety outcomes, similar rates of intracranial hemorrhage (RR = 0.98; 95% CI:0.57-1.69; I2 = 21%), major bleeding (RR = 0.78; 95% CI:0.40-1.51; I2 = 0%), and mortality (RR = 0.94; 95% CI:0.61-1.45; I2 = 0%) were observed. There were no subgroup differences, when RCTs and observational studies were separately evaluated. CONCLUSIONS: Early OAC-initiation in acute ischemic stroke patients with non-valvular atrial fibrillation appears to have better efficacy and a similar safety profile compared to later OAC-initiation.

Comparative study of venous thromboembolic prophylaxis strategies in hemorrhagic stroke: A systematic review and network meta-analysis.

BACKGROUND: Venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), are frequent complications in patients with intracerebral hemorrhage (ICH). Various prophylactic strategies have been employed to mitigate this risk, such as heparin, intermittent pneumatic compression (IPC), and graduated compression stockings (GCS). The optimal thromboembolic prophylaxis approach remains uncertain due to the lack of randomized controlled trials (RCTs) comparing all interventions. AIMS: We conducted a network meta-analysis and meta-analysis to systematically review and synthesize evidence from RCTs and non-randomized studies on the efficacy and safety of thromboembolic prophylaxis strategies in hospitalized ICH patients. SUMMARY OF FINDINGS: Our study followed a registered protocol (PROSPERO CRD42023489217) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines incorporating the extension for network meta-analyses. Search for eligible studies was performed up to December 2023. We considered the occurrence of DVT, PE, hematoma expansion (HE), and all-cause mortality as outcome measures. A total of 16 studies, including 7 RCTs and 9 non-randomized studies, were included in the analysis. Network meta-analysis revealed that IPC demonstrated the highest efficacy in reducing DVT incidence (odds ratios (OR) 0.30, 95% confidence interval (CI) 0.08-1.16), particularly considering only RCTs (OR 0.33, 95% CI 0.16-0.67). GCS showed the highest safety profile for HE (OR 0.67, 95% CI 0.14-3.13), but without efficacy. Chemoprophylaxis did not reduce the risk of PE events (OR 1.10, 95% CI 0.17-7.19) with a higher occurrence of HE (OR 1.33, 95% CI 0.60-2.96), but the differences were not significant. CONCLUSION: Our study supports the use of IPC as the primary thromboembolic prophylaxis measure in ICH patients. Further research, including head-to-head RCTs, is needed to strengthen the evidence base and optimize clinical decision-making for thromboembolic prophylaxis in this vulnerable patient population.

Early seizures and risk of epilepsy and death after intracerebral haemorrhage: The MUCH Italy.

INTRODUCTION: It is unclear which patients with non-traumatic (spontaneous) intracerebral haemorrhage (ICH) are at risk of developing acute symptomatic seizures (provoked seizures occurring within the first week after stroke onset; early seizures, ES) and whether ES predispose to the occurrence of remote symptomatic seizures (unprovoked seizures occurring more than 1 week after stroke; post-stroke epilepsy, PSE) and long-term mortality. PATIENTS AND METHODS: In the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) we examined the risk of ES and whether they predict the occurrence of PSE and all-cause mortality in a cohort of patients with first-ever spontaneous ICH and no previous history of epilepsy, consecutively hospitalized in 12 Italian neurological centers from 2002 to 2014. RESULTS: Among 2570 patients (mean age, 73.4 ± 12.5 years; males, 55.4%) 228 (8.9%) had acute ES (183 (7.1%) short seizures and 45 (1.8%) status epilepticus (SE)). Lobar location of the hematoma (OR, 1.49; 95% CI, 1.06-2.08) was independently associated with the occurrence of ES. Of the 2,037 patients who were followed-up (median follow-up time, 68.0 months (25th-75th percentile, 77.0)), 155 (7.6%) developed PSE. ES (aHR, 2.34; 95% CI, 1.42-3.85), especially when presenting as short seizures (aHR, 2.35; 95% CI, 1.38-4.00) were associated to PSE occurrence. Unlike short seizures, SE was an independent predictor of all-cause mortality (aHR, 1.50; 95% CI, 1.005-2.26). DISCUSSION AND CONCLUSION: The long-term risk of PSE and death after an ICH vary according to ES subtype. This might have implications for the design of future clinical trials targeting post-ICH epileptic seizures.

Predictors of severe intracerebral hemorrhage expansion.

BACKGROUND: Severe hematoma expansion (sHE) has the strongest impact on intracerebral hemorrhage (ICH) outcome. We investigated the predictors of sHE. METHODS: Retrospective analysis of ICH patients admitted at nine sites in Italy, Germany, China, and Canada. The following imaging features were analyzed: non-contrast CT (NCCT) hypodensities, heterogeneous density, blend sign, irregular shape, and CT angiography (CTA) spot sign. The outcome of interest was sHE, defined as volume increase >66% and/or >12.5 from baseline to follow-up NCCT. Predictors of sHE were explored with logistic regression. RESULTS: A total of 1472 patients were included (median age 73, 56.6% males) of whom 223 (15.2%) had sHE. Age (odds ratio (OR) per year, 95% confidence interval (CI), 1.02 (1.01-1.04)), Anticoagulant treatment (OR 3.00, 95% CI 2.09-4.31), Glasgow Coma Scale (OR 0.93, 95% CI 0.89-0.98), time from onset/last known well to imaging, (OR per h 0.96, 95% CI 0.93-0.99), and baseline ICH volume, (OR per mL 1.02, 95% CI 1.02-1.03) were independently associated with sHE. Ultra-early hematoma growth (baseline volume/baseline imaging time) was also a predictor of sHE (OR per mL/h 1.01, 95% CI 1.00-1.02). All NCCT and CTA imaging markers were also predictors of sHE. Amongst imaging features NCCT hypodensities had the highest sensitivity (0.79) whereas the CTA spot sign had the highest positive predictive value (0.51). CONCLUSIONS: sHE is common in the natural history of ICH and can be predicted with few clinical and imaging variables. These findings might inform clinical practice and future trials targeting active bleeding in ICH.

Secondary stroke prevention in people with atrial fibrillation: treatments and trials.

Atrial fibrillation is one of the most common cardiac arrhythmias and is a major cause of ischaemic stroke. Recent findings indicate the importance of atrial fibrillation burden (device-detected, subclinical, or paroxysmal and persistent or permanent) and whether atrial fibrillation was known before stroke onset or diagnosed after stroke for the risk of recurrence. Secondary prevention in patients with atrial fibrillation and stroke aims to reduce the risk of recurrent ischaemic stroke. Findings from randomised controlled trials assessing the optimal timing to introduce direct oral anticoagulant therapy after a stroke show that early start (ie, within 48 h for minor to moderate strokes and within 4-5 days for large strokes) seems safe and could reduce the risk of early recurrence. Other promising developments regarding early rhythm control, left atrial appendage occlusion, and novel factor XI inhibitor oral anticoagulants suggest that these therapies have the potential to further reduce the risk of stroke. Secondary prevention strategies in patients with atrial fibrillation who have a stroke despite oral anticoagulation therapy is an unmet medical need. Research advances suggest a heterogeneous spectrum of causes, and ongoing trials are investigating new approaches for secondary prevention in this vulnerable patient group. In patients with atrial fibrillation and a history of intracerebral haemorrhage, the latest data from randomised controlled trials on stroke prevention shows that oral anticoagulation reduces the risk of ischaemic stroke but more data are needed to define the safety profile.

Long-Term Risk of Arterial Thrombosis After Intracerebral Hemorrhage: MUCH-Italy.

BACKGROUND: The identification of patients surviving an acute intracerebral hemorrhage who are at a long-term risk of arterial thrombosis is a poorly defined, crucial issue for clinicians. METHODS: In the setting of the MUCH-Italy (Multicenter Study on Cerebral Haemorrhage in Italy) prospective observational cohort, we enrolled and followed up consecutive 30-day intracerebral hemorrhage survivors to assess the long-term incidence of arterial thrombotic events, to assess the impact of clinical and radiological variables on the risk of these events, and to develop a tool for estimating such a risk at the individual level. Primary end point was a composite of ischemic stroke, myocardial infarction, or other arterial thrombotic events. A point-scoring system was generated by the ß-coefficients of the variables independently associated with the long-term risk of arterial thrombosis, and the predictive MUCH score was calculated as the sum of the weighted scores. RESULTS: Overall, 1729 patients (median follow-up time, 43 months [25th to 75th percentile, 69.0]) qualified for inclusion. Arterial thrombotic events occurred in 169 (9.7%) patients. Male sex, diabetes, hypercholesterolemia, atrial fibrillation, and personal history of coronary artery disease were associated with increased long-term risk of arterial thrombosis, whereas the use of statins and antithrombotic medications after the acute intracerebral hemorrhage was associated with a reduced risk. The area under the receiver operating characteristic curve of the MUCH score predictive validity was 0.716 (95% CI, 0.56-0.81) for the 0- to 1-year score, 0.672 (95% CI, 0.58-0.73) for the 0- to 5-year score, and 0.744 (95% CI, 0.65-0.81) for the 0- to 10-year score. C statistic for the prediction of events that occur from 0 to 10 years was 0.69 (95% CI, 0.64-0.74). CONCLUSIONS: Intracerebral hemorrhage survivors are at high long-term risk of arterial thrombosis. The MUCH score may serve as a simple tool for risk estimation.

Functional outcome improvement from 3 to 12 months after intracerebral hemorrhage.

INTRODUCTION: Most intracerebral hemorrhage (ICH) trials assessed outcome at 3 months but the recovery trajectory of ICH survivors may continue up to 1 year after the index event. We aimed to describe the predictors of functional outcome improvement from 3 to 12 months after ICH. MATERIALS AND METHODS: Retrospective analysis of patients admitted to six European Stroke Centers for supratentorial ICH. Functional outcome was measured with the modified Rankin Scale (mRS) at 3 and 12 months. Predictors of functional outcome improvement were explored with binary logistic regression. RESULTS: We included 703 patients, of whom 245 (34.9%) died within 3 months. Among survivors, 131 (28.6%) had an mRS improvement, 78 (17.0%) had a worse mRS and 249 (54.4%) had a stable functional status at 12 months. Older age and the presence of baseline disability (defined as pre-stroke mRS > 1), were associated with lower odds of functional outcome improvement (Odds Ratio (OR) 0.98 per year increase, 95% Confidence Interval (CI) 0.96-1.00, p = 0.017 and OR 0.45, 95% CI 0.25-0.81, p = 0.008 respectively). Conversely, deep ICH location increased the probability of long term mRS improvement (OR 1.67, 95% CI, 1.07-2.61, p = 0.023). Patients with mild-moderate disability at 3 months (mRS 2-3) had the highest odds of improvement at 12 months (OR 8.76, 95% CI 3.68-20.86, p < 0.001). DISCUSSION AND CONCLUSION: Long term recovery is common after ICH and associated with age, baseline functional status, mRS at 3 months and hematoma location. Our findings might inform future trials and improve long-term prognostication in clinical practice.

Anticoagulation in acute ischemic stroke patients with mechanical heart valves: To bridge or not with heparin. The ESTREM study.

INTRODUCTION: The best therapeutic strategy for patients with mechanical heart valves (MHVs) having acute ischemic stroke during treatment with vitamin K antagonists (VKAs) remain unclear. Being so, we compared the outcomes for: (i) full dose heparin along with VKA (bridging therapy group) and (ii) restarting VKA without heparin (nonbridging group). PATIENTS AND METHODS: For this multicenter observational cohort study, data on consecutive acute ischemic stroke patients with MHV was retrospectively collected from prospective registries. Propensity score matching (PSM) was adopted to adjust for any treatment allocation confounders. The primary outcome was the composite of stroke, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding at 90 days. RESULTS: Overall, 255 out of 603 patients (41.3%) received bridging therapy: 36 (14.1%) had combined outcome, compared with 28 (8.0%) in the nonbridging group (adjusted OR 1.83; 95% CI 1.05-3.18; p = 0.03). Within the bridging group, 13 patients (5.1%) compared to 12 (3.4%) in the nonbridging group had an ischemic outcome (adjusted OR 1.71; 95% CI 0.84-3.47; p = 0.2); major bleedings were recorded in 23 (9.0%) in the bridging group and 16 (4.6%) in the nonbridging group (adjusted OR 1.88; 95% CI 0.95-3.73; p = 0.07). After PSM, 36 (14.2%) of the 254 bridging patients had combined outcome, compared with 23 (9.1%) of 254 patients in the nonbridging group (OR 1.66; 95% CI 0.95-2.85; p = 0.07). CONCLUSION: Acute ischemic stroke patients with MHV undergoing bridging therapy had a marginally higher risk of ischemic or hemorrhagic events, compared to nonbridging patients.

Systemic thrombolysis in patients with acute stroke and active cancer: a systematic review and meta-analysis.

Cancer patients frequently have concomitant cerebrovascular diseases, which significantly worsen their prognosis. Prospective studies validating intravenous thrombolysis (IVT) safety profile in patients with acute ischemic stroke and active cancer are still lacking. Therefore, we aimed to evaluate IVT's efficacy and safety profile in acute ischemic stroke patients with comorbid active cancer. We included in a meta-analysis all relevant published studies, including patients with acute ischemic stroke with or without active cancer and receiving IVT, according to recommendations for IVT treatment for acute ischemic stroke. The primary outcomes were: any intracerebral hemorrhage, all-cause mortality, and good functional outcome reported as modified Rankin Scale (mRS) ≤ 2 at the end of the scheduled follow-up period. We included 11 studies in the meta-analysis. IVT was not associated with a significant increase in the incidence of intracerebral hemorrhage (OR 1.35; 95% CI 0.85-2.14; I2 76%), nor with a significant increase in death for any cause (OR 1.26; 95% CI 0.91-1.75; I2 71%); furthermore, IVT did not influence mRS between cancer and non-active cancer stroke patients (OR 0.72; 95% CI 0.35-1.49; I2 59%). IVT seems safe and effective in patients with ischemic stroke and concomitant cancer. Due to the low overall quality of the evidence, high-quality randomized controlled trials with adequate sample sizes are needed.

Risk Profile of Patients with Spontaneous Cervical Artery Dissection.

OBJECTIVE: Epidemiological data to characterize the individual risk profile of patients with spontaneous cervical artery dissection (sCeAD) are rather inconsistent. METHODS AND RESULTS: In the setting of the Italian Project on Stroke in Young Adults Cervical Artery Dissection (IPSYS CeAD), we compared the characteristics of 1,468 patients with sCeAD (mean age = 47.3 ± 11.3 years, men = 56.7%) prospectively recruited at 39 Italian centers with those of 2 control groups, composed of (1) patients whose ischemic stroke was caused by mechanisms other than dissection (non-CeAD IS) selected from the prospective IPSYS registry and Brescia Stroke Registry and (2) stroke-free individuals selected from the staff members of participating hospitals, matched 1:1:1 by sex, age, and race. Compared to stroke-free subjects, patients with sCeAD were more likely to be hypertensive (odds ratio [OR] = 1.65, 95% confidence interval [CI] = 1.37-1.98), to have personal history of migraine with aura (OR = 2.45, 95% CI = 1.74-3.34), without aura (OR = 2.67, 95% CI = 2.15-3.32), and family history of vascular disease in first-degree relatives (OR = 1.69, 95% CI = 1.39-2.05), and less likely to be diabetic (OR = 0.65, 95% CI = 0.47-0.91), hypercholesterolemic (OR = 0.75, 95% CI = 0.62-0.91), and obese (OR = 0.41, 95% CI = 0.31-0.54). Migraine without aura was also associated with sCeAD (OR = 1.81, 95% CI = 1.47-2.22) in comparison with patients with non-CeAD IS. In the subgroup of patients with migraine, patients with sCeAD had higher frequency of migraine attacks and were less likely to take anti-migraine preventive medications, especially beta-blockers, compared with the other groups. INTERPRETATION: The risk of sCeAD is influenced by migraine, especially migraine without aura, more than by other factors, increases with increasing frequency of attacks, and seems to be reduced by migraine preventive medications, namely beta-blockers. ANN NEUROL 2023;94:585-595.

Timing and Predictors of Recanalization After Anticoagulation in Cerebral Venous Thrombosis.

BACKGROUND AND PURPOSE: Vessel recanalization after cerebral venous thrombosis (CVT) is associated with favorable outcomes and lower mortality. Several studies examined the timing and predictors of recanalization after CVT with mixed results. We aimed to investigate predictors and timing of recanalization after CVT. METHODS: We used data from the multicenter, international AntiCoagulaTION in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT) study of consecutive patients with CVT from January 2015 to December 2020. Our analysis included patients that had undergone repeat venous neuroimaging more than 30 days after initiation of anticoagulation treatment. Prespecified variables were included in univariate and multivariable analyses to identify independent predictors of failure to recanalize. RESULTS: Among the 551 patients (mean age, 44.4±16.2 years, 66.2% women) that met inclusion criteria, 486 (88.2%) had complete or partial, and 65 (11.8%) had no recanalization. The median time to first follow-up imaging study was 110 days (interquartile range, 60-187). In multivariable analysis, older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03-1.07), male sex (OR, 0.44; 95% CI, 0.24-0.80), and lack of parenchymal changes on baseline imaging (OR, 0.53; 95% CI, 0.29-0.96) were associated with no recanalization. The majority of improvement in recanalization (71.1%) occurred before 3 months from initial diagnosis. A high percentage of complete recanalization (59.0%) took place within the first 3 months after CVT diagnosis. CONCLUSION: Older age, male sex, and lack of parenchymal changes were associated with no recanalization after CVT. The majority recanalization occurred early in the disease course suggesting limited further recanalization with anticoagulation beyond 3 months. Large prospective studies are needed to confirm our findings.

Early versus Later Anticoagulation for Stroke with Atrial Fibrillation.

BACKGROUND: The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear. METHODS: We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days. RESULTS: Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days. CONCLUSIONS: In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).

Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis.

Introduction: Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke. Patients and methods: We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group). We compared groups for symptomatic intracranial hemorrhage (sICH, main outcome), any brain hemorrhage, good functional outcome (mRS 0-2 at 3 months), and death. The systematic review followed a predefined protocol (CRD42017060274), and odds ratio (OR) meta-analysis was implemented to compare groups. Results: Thirty-nine patients in dabigatran-reversal group and 300 matched controls were included. Reversal was associated with a non-significant increase in sICH (10.3% vs 6%, aOR = 1.32, 95% CI = 0.39-4.52), death (17.9% vs 10%, aOR = 0.77, 95% CI = 0.12-4.93) and good functional outcome (64.1% vs 52.8%, aOR = 1.41, 95% CI = 0.63-3.19). No hemorrhagic events or deaths were registered in no-reversal group (n = 12). Pooling data from 3 studies after systematic review (n = 1879), reversal carried a non-significant trend for sICH (OR = 1.53, 95% CI = 0.67-3.50), death (OR = 1.53, 95% CI = 0.73-3.24) and good functional outcome (OR = 2.46, 95% CI = 0.85-7.16). Discussion and conclusion: People treated with reperfusion strategies after dabigatran reversal with idarucizumab seem to have a marginal increase in the risk of sICH but comparable functional recovery to matched patients with stroke. Further studies are needed to define treatment cost-effectiveness and potential thresholds in plasma dabigatran concentration for reversal.

Prolonged cardiac monitoring for stroke prevention: A systematic review and meta-analysis of randomized-controlled clinical trials.

Introduction: Prolonged cardiac monitoring (PCM) substantially improves the detection of subclinical atrial fibrillation (AF) among patients with history of ischemic stroke (IS), leading to prompt initiation of anticoagulants. However, whether PCM may lead to IS prevention remains equivocal. Patients and methods: In this systematic review and meta-analysis, randomized-controlled clinical trials (RCTs) reporting IS rates among patients with known cardiovascular risk factors, including but not limited to history of IS, who received PCM for more than 7 days versus more conservative cardiac rhythm monitoring methods were pooled. Results: Seven RCTs were included comprising a total of 9048 patients with at least one known cardiovascular risk factor that underwent cardiac rhythm monitoring. PCM was associated with reduction of IS occurrence compared to conventional monitoring (Risk Ratio: 0.76; 95% CI: 0.59-0.96; I 2 = 0%). This association was also significant in the subgroup of RCTs investigating implantable cardiac monitoring (Risk Ratio: 0.75; 95% CI: 0.58-0.97; I 2 = 0%). However, when RCTs assessing PCM in both primary and secondary prevention settings were excluded or when RCTs investigating PCM with a duration of 7 days or less were included, the association between PCM and reduction of IS did not retain its statistical significance. Regarding the secondary outcomes, PCM was related to higher likelihood for AF detection and anticoagulant initiation. No association was documented between PCM and IS/transient ischemic attack occurrence, all-cause mortality, intracranial hemorrhage, or major bleeding. Conclusion: PCM may represent an effective stroke prevention strategy in selected patients. Additional RCTs are warranted to validate the robustness of the reported associations.