European Stroke Journal最新文献

Background: Limited studies have provided guidance on the optimal systolic blood pressure (SBP) after mechanical thrombectomy (MT) in acute ischemic stroke patients. In the Clevidipine Infusion for Blood Pressure Management After Successful Revascularization in Acute Ischemic Stroke (CLEVER) trial, our aim was to study the safety and efficacy of intensive SBP control with a Clevidipine infusion as the first-line agent.

Methods: The CLEVER trial was an investigator-initiated, single-center, open-label, randomized, controlled trial. Patients were randomized 1:1 to a SBP goal after successful MT (mTICI 2c or greater) of either 90-120mmHg (Intensive BP Management) or 90-160mmHg (Standard BP Management). The primary outcomes were time to target blood pressure and incidence of any hemorrhagic conversion at 24 hours.

Results: Between October 2021 and December 2023, 80 eligible patients were enrolled, 40 each into the intensive BP and the standard BP management cohorts. Overall, 72% of all BP measurements in the intensive BP management group were within the target range, compared to 93% in the standard BP management group (p<0.001). The median time from the initiation of Clevidipine infusion until reaching the target SBP was significantly shorter in the standard BP management group, 10 minutes [IQR 5.0-45.0] versus 20 IQR 12.5-42.5] (95%CI:5.0-20.0, p=0.002). The incidence of hemorrhagic transformation per core lab was not significantly different in the intensive BP management group (32.5%) and the standard BP management group (35.0%); adjusted OR (0.93 [95%CI, 0.30-2.85]; p=0.89).

Conclusion: In the randomised CLEVER trial, intensive BP control using clevidipine after MT failed to reduce the rate of haemorrhagic conversion or sICH and resulted in a numerically lower rate of good clinical outcome compared to standard BP control. Clevidipine was well tolerated in both cohorts and demonstrated a similar safety profile. Larger studies are needed to understand the efficacy and safety of clevidipine for BP control and the optimal BP threshold after MT.

Introduction: Anaemia is an established risk factor for poor outcome in intracerebral haemorrhage and ischaemic stroke. We examined whether anaemia predicts poor outcome in cerebral venous thrombosis (CVT).

Patients and methods: We used data of the DOAC-CVT study, which was an international, prospective observational cohort study in adult patients with CVT that ran from January 2021 to January 2024. Anaemia at admission was defined according to World Health Organization criteria. Poor outcome was defined as modified Rankin Scale (mRS) 3-6 at 6-months. Binary logistic regression, adjusted for age, recent delivery/puerperium, income country, cancer and intracranial haemorrhage, was applied.

Results: Of 619 patients in DOAC-CVT, 583 patients were included, of whom 157 (27%) had anaemia. Compared to patients without anaemia, patients with anaemia were slightly younger (median age 40 vs. 42 years), more often female (76% vs. 59%), from middle income countries (36% vs. 21%), more often had intracranial haemorrhage (48% vs. 32%) and cancer (5% vs. 2%). Anaemia was associated with poor functional outcome (mRS 3-6, 10% vs. 5%, aOR: 2.20, 95% Cl, 1.01-4.81), but not with mortality (3% vs. 1%, aOR: 3.54, 95% Cl, 0.68-18.31). When stratified by severity, moderate to severe anaemia was associated with poor functional outcome (aOR 2.88, 95% Cl, 1.14-7.38), but mild anaemia was not (aOR 1.64, 95% Cl, 0.60-4.55).

Discussion and conclusion: Anaemia at admission, especially moderate to severe, is a predictor for poor functional outcome in patients with CVT, highlighting the need for further studies on potential interventions.

Introduction: Despite the considerable success of endovascular treatment (EVT) in stroke due to large vessel occlusion (LVO), many patients still experience poor outcomes, highlighting the need for additional therapeutic approaches. In a preliminary study [COmbination of Targeted temperature management and Thrombectomy after acute Ischemic Stroke (COTTIS trial)] safety and feasibility of rapid transnasal cooling to 35°C prior to EVT in LVO was established. The objective of this investigation was to determine whether this combination improves outcomes based on a matched-pair analysis of our prospective EVT registry.

Patients and methods: A single-center matched-pair analysis was conducted on patients with EVT in LVO. Hypothermic patients were recruited from the prospective COTTIS trial. Normothermic patients were recruited from a prospective stroke registry on EVT in LVO at our institution. Matching parameters were age, gender, National Institutes of Health Stroke Scale (NIHSS), Alberta Stroke Program Early CT Score (ASPECTS), occlusion type/side and Thrombolysis in Cerebral Infarction (TICI) score. Primary outcome was a favorable neurological outcome [modified Rankin Score (mRS) of 0-2] at 90 days.

Results: A total of 66 patients were analyzed (hypothermia: 22; standard care: 44). Temperature profiles differed by a mean of 1°C. A favorable neurological outcome was reached more often in hypothermia (68.2%) compared with standard care (29.5%) [odds ratio 5.1 (95% confidence interval 1.69; 15.38)] (p = 0.004). In the shift analysis in hypothermic patients the probability of attaining a higher score on the mRS was reduced significantly. Safety outcomes did not differ between groups.

Conclusion: Our comparative analysis on periinterventional mild hypothermia in EVT suggests a beneficial effect on clinical outcome. Despite the small sample size the effect size is surprisingly high, which needs critical consideration. Randomized controlled trials are needed to validate these findings.

Trial registration: The COTTIS study was registered at DKRS: DRKS-ID DRKS00023573.

Introduction: Post-stroke depression (PSD) frequently occurs after acute stroke and negatively affects rehabilitation. Dopamine has beneficial effects on motivation and emotional stability. In stroke patients, low dopamine levels are linked to PSD. This study investigated whether levodopa treatment during in-hospital rehabilitation impacts PSD compared to placebo.

Patients and methods: ESTREL-Depression was a pre-planned analysis of the multicenter, randomized, double-blind, placebo-controlled ESTREL trial. Participants with an acute ischemic or hemorrhagic stroke were randomly assigned to receive either levodopa/carbidopa (100/25 mg) or placebo three times daily for 39 days. All ESTREL participants with (1) information about the presence or absence of depression at three months and (2) who took at least 80% of the study medication were eligible for the study. Participants with a history of depression were excluded. For the primary outcome, the presence of PSD was defined as having a T-score of ≥55 in the Patient-Reported Outcomes Measurement Information System short-form depression-4a 3 months after randomization. Binary logistic regression was performed to assess the effect of levodopa on PSD.

Results: The study included 407 ESTREL participants (median age 72, 60% male), 209 receiving levodopa, and 198 receiving placebo. At 3 months, the frequency and odds of PSD did not differ between the levodopa group (26%) and the placebo group (28%) (OR = 0.93, 95% CI, 0.60-1.43).

Conclusion: In the ESTREL-Depression study, treatment with levodopa had no impact on the occurrence of PSD.

Clinical trial registration: ClinicalTrials.gov: NCT03735901 (https://clinicaltrials.gov/study/NCT03735901).

Introduction: Inequity in stroke care in Europe has previously been reported despite the existence of evidence-based cost-effective interventions for both prevention and treatment. This report aims to provide comprehensive data on stroke care in Europe in 2023 and explore associations to European regions, organisational and economic factors.

Patients and methods: The Stroke Service Tracker, an annually collected survey-based dataset of aggregate summary data from participating European nations, was used with key performance indicators (KPIs) from the Stroke Action Plan for Europe (SAP-E). European regions were defined based on United Nations Geoscheme regions. Gross domestic product (GDP) per capita and healthcare spending per capita were collected based on World Bank data.

Results: A total of 1,460,630 stroke events were reported in 2023 from 52 nations. Significant inequity was present in all data points and data quality varied significantly. Twenty (43.5%) nations have a national stroke plan in place, and in 19 (41.3%) work is ongoing. Quality programmes have been implemented in 20 (43.5%) nations. Implementation of a national stroke plan or a quality programme was associated with achieving more SAP-E KPIs (P < .001). There were regional differences in the number of met KPIs (P < .001). Both GDP and healthcare spending per capita were strongly correlated to meeting KPIs.

Conclusion: The inequity in stroke care persists in Europe. Implementation of a national stroke plan and a quality programme is associated with meeting more KPIs; however, economic factors may pose limitations. Access to high-quality data will support decision-making towards evidence-based and cost-effective care.

Introduction: A recent meta-analysis, including the TIMING study, found favourable short-term outcomes after early initiation of a direct-acting oral anticoagulant (DOAC), as compared to delayed initiation, following acute ischaemic stroke in patients with atrial fibrillation. We aimed to investigate 1-year outcomes after early vs delayed DOAC initiation in the TIMING study population and a concurrent observational cohort.

Patients and methods: In TIMING, adults with atrial fibrillation were randomised to initiation of DOAC either within 4 days or at 5-10 days after acute ischaemic stroke. The non-randomised cohort comprised patients with acute ischaemic stroke and atrial fibrillation, observed in the Swedish Stroke Register concurrently with the TIMING study and initiating DOAC within 4 or 5-10 days, respectively. Outcomes in both populations were acute ischaemic stroke, symptomatic intracerebral haemorrhage or death, as a composite and individually, analysed using Cox regression models, with adjustment for risk factors in the observational cohort.

Results: In the TIMING population (n = 888), the composite outcome at 365 days occurred in 64/450 patients (14.2%) with early DOAC initiation and 66/438 (15.1%) with delayed, unadjusted hazard ratio 0.92 (95% CI, 0.66-1.30). In the observational cohort (n = 8951), the composite outcome at 365 days occurred in 1227/6671 (18.4%) patients initiating DOAC early and 511/2280 (22.4%) in the delayed group, adjusted hazard ratio 0.80 (0.69-0.91).

Discussion: At 1-year follow-up, early initiation of DOAC remained safe and effective with no increase in symptomatic intracerebral haemorrhage. The results support early DOAC initiation in patients with acute ischaemic stroke and atrial fibrillation.

Introduction: Intracranial aneurysms are often unruptured and two-thirds of patients with unruptured intracranial aneurysms (UIAs) are women. Rupture of an intracranial aneurysm causes aneurysmal subarachnoid haemorrhage (aSAH). While risk factors for aSAH have been extensively studied, those for UIA remain less well understood. We performed a systematic review and meta-analysis to identify risk factors for the presence of saccular UIAs and assess potential sex differences.

Patients and methods: We conducted a systematic review and meta-analysis of cohort, case-control, and cross-sectional studies on risk factors for UIA up to March 2024. Assessed risk factors included smoking, hypertension, alcohol use, diabetes, hypercholesterolaemia, physical activity, and body mass index. We performed random-effects meta-analyses to calculate pooled odds ratios (ORs) and 95% CIs for each risk factor.

Results: We identified 21 studies reporting on overall 347 907 participants and 8698 UIA cases. Hypertension (OR 1.72, 95% CI, 1.42-2.09) and smoking (OR 1.47, 95% CI, 1.11-1.95) were associated with the presence of UIAs. No statistically significant associations were found for the other assessed risk factors. Among 18 studies that included both sexes, only one provided sex-stratified results, preventing us from assessing potential sex differences.

Discussion: Future research should consistently report sex-stratified results to enable investigation of potential sex differences in UIA risk factors and further explore female-specific risk factors that may contribute to the high female preponderance in UIA.

Conclusion: Hypertension and smoking are associated with an increased risk of UIAs. The lack of sex-stratified data limits conclusions about sex-specific risk profiles.

Introduction: Identification of factors associated with haematoma expansion (HE) in patients with primary intracerebral haemorrhage (ICH) is crucial for optimization of management and therapeutic strategies. We investigated whether such factors differed according to supratentorial ICH location, comparing deep versus lobar ICH.

Methods: Retrospective analysis of patients with primary ICH admitted at nine sites. HE was defined as growth ≥6 mL and/or ≥33% from baseline to follow-up imaging. We evaluated independent associations using multivariable logistic regression models adjusted for age, sex, baseline haematoma volume, anticoagulants and antiplatelets use and other relevant confounders identified in univariate analyses.

Results: A total of 1768 patients were included (mean age 70 years, 56% males) of whom 1020 (58%) had deep and 748 (42%) had lobar ICH; HE occurred in 531 (30%) patients (28% deep and 33% lobar ICH). Age and baseline haematoma volume were shared predictors of HE in lobar and deep ICH. Anticoagulant use (OR = 1.61;95%, 1.04-2.50) and lower Glasgow Come Scale (OR = 0.91;95%CI, 0.85-0.96) were associated with HE only in lobar ICH, whereas the associations between systolic blood pressure >140 mmHg (OR = 1.53;95%CI, 1.03-2.29) and presentation before 3 h from onset (OR = 1.40;95%CI, 1.02-1.92) and HE were observed only in patients with deep ICH.

Conclusions: Some factors associated with HE were shared between deep and lobar ICH whereas others appeared to be location-specific. Our findings may reflect differences in the pathophysiology of HE according to ICH location and might improve the stratification of HE risk in clinical practice or randomized trials.

Background: Breakthrough ischaemic stroke during oral anticoagulation (OAC) for atrial fibrillation (AF) represents a major therapeutic challenge, especially in patients with cancer, who face competing risks of thrombosis and bleeding. This study investigated the impact of cancer on 90-day outcomes after ischaemic stroke on OAC.

Patients and methods: We analysed patients with AF who experienced ischaemic stroke while on continuous OAC enrolled in the international retrospective ASPERA-R study, comprising 35 stroke centres across 9 countries. Inverse probability weighting was applied to adjust for baseline imbalances, and weighted Cox, ordinal logistic and generalised linear models were used to estimate adjusted 90-day risks for the primary (ischaemic stroke or TIA), secondary (mRS shift, vascular/all-cause death) and safety (moderate-to-severe bleeding, ICH, 24-h haemorrhagic transformation) outcomes.

Results: Among 1649 included patients (mean age 78.0 ± 10.7 years; 45.8% male), 247 (15.0%) had cancer, of whom 87 (35.2%) had active cancer and 160 (64.8%) were in remission. After weighting, patients with cancer had a significantly higher 90-day risk of new ischaemic stroke or TIA (8.2% vs 2.8%; adjusted hazard ratio [aHR] 2.56; 95% CI, 1.59-4.13; P < .001) and worse 90-day mRS score distribution (adjusted odds ratio 1.29; 95% CI, 1.08-1.54; P = .005) than those without cancer. Active cancer conferred a > 4-fold higher risk of new ischaemic stroke or TIA (HR 4.48, 95% CI, 2.46-8.13; P < .001) and nearly 3-fold higher risk of moderate-to-severe bleeding (HR 2.77; 95% CI, 1.30-5.88; P = .008). Patients with cancer in remission showed increased ischaemic risk (HR 2.60; 95% CI, 1.59-5.25; P = .001) but not bleeding risk. Haematological malignancies carried a higher risk for both new ischaemic stroke or TIA (HR 3.06; 95% CI, 1.69-5.54; P = .001) and moderate-to-severe bleeding (HR 3.47, 95% CI, 1.57-7.70; P = .006) compared to solid malignancies.

Conclusion: Cancer, particularly active and haematological malignancies, substantially worsens 90-day prognosis after breakthrough stroke on OAC, underscoring the need for refined risk stratification and tailored secondary prevention.

Trial registration: URL: www.clinicaltrials.gov; Unique identifier: NCT06823466.

Background: Access to reperfusion therapies and stroke unit (SU) admission remains heterogeneous across Europe. Mapping tools can reveal service gaps and guide implementation strategies. MAPSTROKE provides regional mapping of existing stroke centres and identifies potential new sites in underserved areas.

Aims: To apply a computational strategy to the Italian stroke care system to estimate national coverage for reperfusion therapies and quantify SU bed capacity under current constraints.

Methods: Using MAPSTROKE geospatial modelling, we assessed (1) 45-min access to a hospital providing reperfusion treatment and (2) SU bed coverage limited by capacity. Population and stroke incidence data for 2023 were mapped on a hexagonal grid combining sources from the Italian Ministry of Health and the Kontur Dataset. Hospitals were classified as Comprehensive (CSC), Primary (PSC), Acute Stroke-Ready (ASRH) or Potential Acute Stroke Centres (PASC). Isochrones of 45 min were generated for hospitals performing reperfusion. Regional coverage was estimated, and a Partial Set Covering identified the minimal number of PASCs required to achieve ≥ 90% coverage. Stroke unit capacity was estimated using bed counts and mean length of stay (LOS).

Results: Among 535 hospitals (80 CSCs, 132 PSCs, 22 ASRHs, 301 PASCs), 91.7% of strokes were within 45 min of a hospital providing reperfusion treatment. Seven regions were below 90%, 6 achieved this target after optimisation. National SU capacity covered 79.2% of annual incidence, with a gap of 255 beds (158 with ideal LOS).

Conclusions: The MAPSTROKE project reveals adequate reperfusion access but critical SU capacity disparities, underscoring the need for coordinated national strategies.