Frequency of ischaemic stroke and intracranial haemorrhage in patients with reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) - A systematic review.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) may cause ischaemic stroke and intracranial haemorrhage. The aim of our study was to assess the frequency of the afore-mentioned outcomes. METHODS: We performed a PROSPERO-registered (CRD42022355704) systematic review and meta-analysis accessing PubMed until 7 November 2022. The inclusion criteria were: (1) original publication, (2) adult patients (≥18 years), (3) enrolling patients with PRES and/or RCVS, (4) English language and (5) outcome information. Outcomes were frequency of (1) ischaemic stroke and (2) intracranial haemorrhage, divided into subarachnoid haemorrhage (SAH) and intraparenchymal haemorrhage (IPH). The Cochrane Risk of Bias tool was used. RESULTS: We identified 848 studies and included 48 relevant studies after reviewing titles, abstracts and full text. We found 11 studies on RCVS (unselected patients), reporting on 2746 patients. Among the patients analysed, 15.9% (95% CI 9.6%-23.4%) had ischaemic stroke and 22.1% (95% CI 10%-39.6%) had intracranial haemorrhage. A further 20.3% (95% CI 11.2%-31.2%) had SAH and 6.7% (95% CI 3.6%-10.7%) had IPH. Furthermore, we found 28 studies on PRES (unselected patients), reporting on 1385 patients. Among the patients analysed, 11.2% (95% CI 7.9%-15%) had ischaemic stroke and 16.1% (95% CI 12.3%-20.3%) had intracranial haemorrhage. Further, 7% (95% CI 4.7%-9.9%) had SAH and 9.7% (95% CI 5.4%-15%) had IPH. CONCLUSIONS: Intracranial haemorrhage and ischaemic stroke are common outcomes in PRES and RCVS. The frequency reported in the individual studies varied considerably.

Outcome Comparison of Endovascular Treatment for Acute Large Vessel Occlusion Due to Large Artery Atherosclerosis and Cardioembolism in the Chinese Population: Data from the ANGEL Registry.

Background and Purpose: Studies on outcome comparison after endovascular treatment (EVT) for large vessel occlusion (LVO) between large artery atherosclerosis (LAA) and cardioembolism (CE) in the Asian population are scarce. We aimed to compare the baseline characteristics and clinical outcomes after EVT for anterior circulation LVO with LAA and CE in the Chinese population. Methods: Patients were selected from the ANGEL registry and divided into LAA and CE groups. The primary outcome was the 90-day modified Rankin Scale (mRS) 0-2. The secondary outcomes were 90-day mRS distribution, 90-day mRS 0-1, 90-day mRS 0-3, and early neurological improvement. The safety outcomes included death, symptomatic intracranial hemorrhage, and any intracranial hemorrhage. We conducted logistic regression models with adjustments to compare the outcomes. Results: A total of 632 patients were included, of whom, 488 were in the LAA group and 144 were in the CE group. No significant difference in 90-day mRS 0-2 was observed between LAA and CE groups (55.7%vs.43.1%, odds ratio[OR] 1.19, 95% confidence interval(CI), 0.92-1.53, P=0.190). The LAA group exhibited a higher frequency of mRS 0-3 compared to the CE group (69.1% vs 32.6%, OR1.32, 95% CI 1.02-1.72, P=0.038). However, the incidence of death within 90 days did not significantly differ between the LAA and CE groups (10.9%vs.24.3%, OR0.91, 95% CI0.66-1.25, P=0.545), nor did the occurrences of symptomatic intracranial hemorrhage(SICH) (4.5%vs.9.7%,OR1.08, 95% CI 0.65-1.78, P=0.779) or intracranial hemorrhage(ICH) (21.9%vs.30.6%, OR 0.94, 95% CI0.71-1.25, P=0.680). Moreover, no significant disparities were detected in other outcomes between the two groups (All P>0.05). Conclusion: In the ANGEL registry, a higher prevalence of patients undergoing EVT for acute anterior circulation LVO with LAA was found than those with CE. However, our study revealed that the efficacy and safety of EVT remained consistent regardless of the stroke's etiology such as LAA or CE.

Technical and clinical outcomes of thrombectomy in patients with acute medium vessel occlusion and large vessel occlusion; sub-analyses of Japan Trevo registry.

BACKGROUND: Little is known about endovascular therapy (EVT) for patients with medium vessel occlusion (MeVO) and more work is needed to establish its efficacy and to understand hemorrhagic complications. METHODS: We analyzed the Japan Trevo Registry, which enrolled patients with acute stroke who underwent EVT using Trevo Retriever alone or in combination with an aspiration catheter. The primary outcome was effective reperfusion, and the secondary outcome was modified Rankin scale 0-2 at 90 days. Safety outcomes, including intracranial hemorrhage (ICH), were evaluated using a subgroup analyses focused on any ICH. RESULTS: Among 1041 registered patients, 1025 patients were analyzed. 253 patients had MeVOs, and the majority (89.3%) had middle cerebral artery segment 2 (M2). The median National Institutes of Health Stroke Scale scores at admission were 15 and 19 for the MeVO and LVO groups (p < 0.0001). The primary outcome was 88.9% in MeVO vs. 91.8% in LVO group: adjusted odds ratio (aOR) [95% confidence interval (CI)] 0.60 [0.35-1.03], p = 0.07, and the secondary outcome was 43.2% vs. 42.2%, and the aOR [95%CI] was 0.70 [0.48-1.002], p = 0.051. However, the incidence of any ICH was more prominent in MeVO than in LVO group (35.7% vs. 28.8%, aOR [95%CI] 1.54 [1.10-2.15], p = 0.01). In subgroup analyses, the incidences of any ICH in MeVO group were generally higher than those in LVO group. CONCLUSIONS: The effective reperfusion rate did not differ significantly between MeVO and LVO groups. Future development of devices and treatments for MeVO with fewer hemorrhagic complications is desirable.

Trends in cerebral venous thrombosis before and during the COVID-19 pandemic: Analysis of the National Inpatient Sample.

OBJECTIVES: We sought to provide updated incidence and trend data for cerebral venous thrombosis (CVT) in the United States from 2016-2020, examine the impact of the COVID-19 pandemic on CVT, and identify predictors of in-hospital mortality. MATERIALS AND METHODS: Validated ICD-10 codes were used to identify discharges with CVT in the National Inpatient Sample (NIS). Sample weights were applied to generate nationally representative estimates, and census data were used to compute incidence rates. The first wave of the COVID-19 pandemic was defined as January-May 2020. Trend analysis was completed using Joinpoint regression. RESULTS: From 2016 to 2020, the incidence of CVT increased from 24.34 per 1,000,000 population per year (MPY) to 33.63 per MPY (Annual Percentage Change (APC) 8.6 %; p < 0.001). All-cause in-hospital mortality was 4.9 % [95 % CI 4.5-5.4]. On multivariable analysis, use of thrombectomy, increased age, atrial fibrillation, stroke diagnosis, infection, presence of prothrombotic hematologic conditions, lowest quartile of income, intracranial hemorrhage, and male sex were associated with in-hospital mortality. CVT incidence was similar comparing the first 5 months of 2020 and 2019 (31.37 vs 32.04; p = 0.322) with no difference in median NIHSS (2 [IQR 1-10] vs. 2 [1-9]; p = 0.959) or mortality (4.2 % vs. 5.6 %; p = 0.176). CONCLUSIONS: CVT incidence increased in the US from 2016 to 2020 while mortality did not change. Increased age, prothrombotic state, stroke diagnosis, infection, atrial fibrillation, male sex, lowest quartile of income, intracranial hemorrhage, and use of thrombectomy were associated with in-hospital mortality following CVT. During the first wave of the COVID-19 pandemic, CVT volumes and mortality were similar to the prior year.

Thrombolytic Treatment in Wake-Up Stroke: A Propensity Score-Matched Analysis of Treatment Effectiveness in the Norwegian Stroke Registry.

BACKGROUND: Previous clinical trials found improved outcome of thrombolytic treatment in patients with ischemic wake-up stroke (WUS) selected by advanced imaging techniques. The authors assessed the effectiveness of thrombolytic treatment in patients with WUS in a nationwide stroke registry. METHODS AND RESULTS: Using propensity score matching, the authors assessed the effectiveness and safety of thrombolytic treatment versus no thrombolytic treatment in 726 patients (363 matched pairs) with WUS in the Norwegian Stroke Registry in 2014 to 2019. Thrombolytic treatment in WUS versus known-onset stroke was compared in 730 patients (365 matched pairs). Functional outcomes were assessed by the modified Rankin Scale (mRS) at 3 months. A significant benefit of thrombolytic treatment in WUS was seen in ordinal analysis (odds ratio [OR], 1.48 [95% CI, 1.15-1.91]; P=0.003) and for mRS 0 to 2 (OR, 1.81 [95% CI, 1.29-2.52]; P=0.001) but not for mRS 0 or 1 (OR, 1.32 [95% CI, 1.00-1.74]; P=0.050). The proportion of patients with mRS 0 or 1 was lower in patients with WUS who underwent thrombolysis versus those with known-onset stroke (50.4% versus 59.5%; OR, 0.69 [95% CI, 0.52-0.93]; P=0.013), while outcomes were similar between groups for mRS 0 to 2 and ordinal analysis. Symptomatic intracranial hemorrhage after thrombolytic treatment occurred in 4.4% of patients with WUS and 3.9% of patients with known-onset stroke (OR, 1.14 [95% CI, 0.54-2.41]; P=0.726). CONCLUSIONS: Thrombolytic treatment in patients with WUS was associated with improved functional outcome compared with patients with no thrombolytic treatment and was not associated with increased rates of symptomatic intracranial hemorrhage compared with known-onset stroke. The results indicate that thrombolytic treatment is effective and safe in WUS in a real-life setting.

Changing or Retaining Direct Oral Anticoagulant After Ischemic Stroke Despite Direct Oral Anticoagulant Treatment.

BACKGROUND: The optimal antithrombotic strategies for patients with atrial fibrillation who experience ischemic stroke (IS) despite direct oral anticoagulant (DOAC) therapy remain inconclusive. This study compared outcomes for patients with DOAC treatment failure who changed or retained their prestroke DOAC. METHODS AND RESULTS: This retrospective cohort study analyzed data from the National Health Insurance Research Database from 2012 to 2020. Patients with atrial fibrillation who experienced IS during DOAC therapy were assigned to either (1) the DOAC-change group: changing prestroke DOAC or (2) the DOAC-retain group: retaining prestroke DOAC. The primary outcome was a composite of recurrent IS and transient ischemic attack. The secondary outcomes included intracranial hemorrhage, major bleeding, systemic thromboembolism, and all-cause death. Propensity score-based inverse probability of treatment weighting was applied to balance the baseline characteristics between the DOAC-change and DOAC-retain groups. The Cox proportional hazards model compared the risk of outcomes between the 2 groups. In total, 1979 patients were enrolled (609 DOAC-change patients and 1370 DOAC-retain patients). The incidence rates of recurrent IS or transient ischemic attack were 7.20 and 6.56 per 100 person-years in the DOAC-change and DOAC-retain groups, respectively (hazard ratio [HR], 1.07 [95% CI, 0.87-1.30]). A nonsignificantly higher incidence rate of intracranial hemorrhage was observed in the DOAC-change group compared with the DOAC-retain group (0.75 versus 0.53 per 100-person-years; HR, 1.49 [95% CI, 0.78-2.83]). The systemic thromboembolism, major bleeding, and death rates were comparable between the DOAC-change and DOAC-retain groups. CONCLUSIONS: Changing prestroke DOAC does not reduce the risk of recurrent cerebral ischemia in patients with atrial fibrillation who develop IS during DOAC therapy. However, future studies should continue to observe the potential trends of increased intracranial hemorrhage risk.

Factors associated with the initial intracranial hemorrhage occurrence in patients with cerebral venous thrombosis.

OBJECTIVES: Studies focusing on intracranial hemorrhage (ICH) in patients with cerebral venous thrombosis (CVT) are limited; thus, we aimed to identify factors associated with the occurrence of ICH in Thai patients with CVT. METHODS: This retrospective cohort study recruited patients with CVT admitted to a tertiary university-based hospital between 2002 and 2022. The baseline characteristics, clinical presentations, radiographic findings, and etiologies were compared between the ICH and non-ICH groups. The factors with p < 0.2 in the univariate analysis were further analyzed using multivariable logistic regression analysis to identify independent factors associated with ICH in patients with CVT. RESULTS: Of 228 screenings, 202 patients were eligible. The incidence rate of ICH was 36.63%. The ICH group showed a higher prevalence of focal neurological deficits (63.51% vs. 26.56%, p < 0.001), seizures (68.92% vs. 21.88%, p < 0.001), dependency status at admission (60.81% vs. 39.84%, p = 0.004), superior sagittal sinus thrombosis (71.62% vs. 39.07%, p < 0.001), superficial cortical vein thrombosis (36.49% vs. 10.16%, p < 0.001), and hormonal use (17.57% vs. 7.03%, p = 0.021) than the non-ICH group. In contrast, the ICH group showed a lower prevalence of isolated increased intracranial pressure (10.81% vs. 21.88%, p = 0.048) than the non-ICH group. Seizures (adjusted odds ratio [aOR], 4.537; 95% confidence interval [CI], 2.085-9.874; p < 0.001), focal neurological deficits (aOR, 2.431; 95% CI, 1.057-5.593; p = 0.037), and superior sagittal sinus thrombosis (aOR, 1.922; 95% CI, 1.913-4.045; p = 0.045) were independently associated with ICH in the multivariable logistic regression analysis. CONCLUSIONS: Seizures, focal neurological deficits, and superior sagittal sinus thrombosis are associated with ICH in patients with CVT.

Intravenous Thrombolysis Before Endovascular Treatment in Posterior Circulation Occlusions: A MR CLEAN Registry Study.

BACKGROUND: The effectiveness of intravenous thrombolysis (IVT) before endovascular treatment (EVT) has been investigated in randomized trials and meta-analyses. These studies mainly concerned anterior circulation occlusions. We aimed to investigate clinical, technical, and safety outcomes of IVT before EVT in posterior circulation occlusions in a nationwide registry. METHODS: Patients were included from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), a nationwide, prospective, multicenter registry of patients with acute ischemic stroke due to a large intracranial vessel occlusion receiving EVT between 2014 and 2019. All patients with a posterior circulation occlusion were included. Primary outcome was a shift toward better functional outcome on the modified Rankin Scale at 90 days. Secondary outcomes were favorable functional outcome (modified Rankin Scale scores, 0-3), occurrence of symptomatic intracranial hemorrhages, successful reperfusion (extended Thrombolysis in Cerebral Ischemia ≥2B), first-attempt successful reperfusion, and mortality at 90 days. Regression analyses with adjustments based on univariable analyses and literature were applied. RESULTS: A total of 248 patients were included, who received either IVT (n=125) or no IVT (n=123) before EVT. Results show no differences in a shift on the modified Rankin Scale (adjusted common odds ratio, 1.04 [95% CI, 0.61-1.76]). Although symptomatic intracranial hemorrhages occurred more often in the IVT group (4.8% versus 2.4%), regression analysis did not show a significant difference (adjusted odds ratio, 1.65 [95% CI, 0.33-8.35]). Successful reperfusion, favorable functional outcome, first-attempt successful reperfusion, and mortality did not differ between patients treated with and without IVT. CONCLUSIONS: We found no significant differences in clinical, technical, and safety outcomes between patients with a large vessel occlusion in the posterior circulation treated with or without IVT before EVT. Our results are in line with the literature on the anterior circulation.

Joblessness, decreased income, and disability in intensive care unit survivors of nontraumatic intracranial hemorrhage in South Korea.

OBJECTIVES: To examine the proportions of unemployment, decreased household income, and newly acquired disability, and their impact on long-term mortality after intensive care unit (ICU) admission due to nontraumatic intracranial hemorrhage (IH). MATERIALS AND METHODS: This nationwide population-based retrospective cohort study enrolled adult patients admitted to the ICU because of nontraumatic IH between 2010 and 2018 in South Korea. Patients who were alive ≥365 days after ICU admission were defined as nontraumatic IH survivors. RESULTS: In total, 104,086 nontraumatic IH survivors were included in the final analysis. Among them, 7,225 (6.9 %) experienced job loss, 25,709 (24.7 %) experienced decreased household income, and 20,938 (20.1 %) had newly acquired disabilities, of whom 14,188 (13.6 %) had newly acquired brain disabilities. Male sex, increased duration of intensive care unit stay, comorbid status, hospital admission through the emergency room, nontraumatic intracerebral hemorrhage, receipt of surgery, mechanical ventilatory support, and increased total cost of hospitalization were associated with job loss, decreased household income, and newly acquired disabilities. However, these changes were not significantly associated with 2-year all-cause mortality (adjusted hazard ratio: 1.00, 95 % confidence interval: 0.95, 1.06; P = 0.997). CONCLUSIONS: Many nontraumatic IH survivors experienced unemployment, decreased household income, and newly acquired disability one year after ICU admission in South Korea. Some factors were potential risk factors for these changes, but the changes were not associated with 2-year all-cause mortality.

Risk of Bleeding Following Non-Vitamin K Antagonist Oral Anticoagulant Use in Patients With Acute Ischemic Stroke Treated With Alteplase.

Importance: Current guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non-vitamin K antagonist oral anticoagulants (NOACs). Objective: To evaluate the risk of bleeding and mortality after alteplase treatment for acute ischemic stroke among patients treated with NOACs compared to those not treated with NOACs. Design, Setting, and Participants: This nationwide, population-based cohort study was conducted in Taiwan using data from Taiwan's National Health Insurance Research Database from January 2011 through November 2020 and included 7483 patients treated with alteplase for acute ischemic stroke. A meta-analysis incorporating the results of the study with those of previous studies was performed, and the review protocol was prospectively registered with PROSPERO. Exposures: NOAC treatment within 2 days prior to stroke, compared to either no anticoagulant treatment or warfarin treatment. Main Outcomes and Measures: The primary outcome was intracranial hemorrhage after intravenous alteplase during the index hospitalization (the hospitalization subsequent to alteplase administration). Secondary outcomes were major bleeding events and mortality during the index hospitalization. Propensity score matching was used to control potential confounders. Logistic regression was used to estimate the odds ratio (OR) of outcome events. Meta-analysis was performed using a random-effects model. Results: Of the 7483 included patients (mean [SD] age, 67.4 [12.7] years; 2908 [38.9%] female individuals and 4575 [61.1%] male individuals), 91 (1.2%), 182 (2.4%), and 7210 (96.4%) received NOACs, warfarin, and no anticoagulants prior to their stroke, respectively. Compared to patients who were not treated with anticoagulants, those treated with NOACs did not have significantly higher risks of intracranial hemorrhage (risk difference [RD], 2.47% [95% CI, -4.23% to 9.17%]; OR, 1.37 [95% CI, 0.62-3.03]), major bleeding (RD, 4.95% [95% CI, -2.56% to 12.45%]; OR, 1.69 [95% CI, 0.83-3.45]), or in-hospital mortality (RD, -4.95% [95% CI, -10.11% to 0.22%]; OR, 0.45 [95% CI, 0.15-1.29]) in the propensity score-matched analyses. Furthermore, the risks of bleeding and mortality were not significantly different between patients treated with NOACs and those treated with warfarin. Similar results were obtained in the meta-analysis. Conclusions and Relevance: In this cohort study with meta-analysis, compared to no treatment with anticoagulants, treatment with NOACs prior to stroke was not associated with a higher risk of intracranial hemorrhage, major bleeding, or mortality in patients receiving intravenous alteplase for acute ischemic stroke.

Stroke and bleeding risk in atrial fibrillation with CHA2DS2-VASC risk score of one: the Norwegian AFNOR study.

BACKGROUND AND AIMS: The benefit of oral anticoagulant (OAC) therapy in atrial fibrillation (AF) and intermediate stroke risk is debated. In a nationwide Norwegian cohort with a non-sex CHA2DS2-VASc risk score of one, this study aimed to investigate (i) stroke and bleeding risk in AF patients with and without OAC treatment, and (ii) the risk of stroke in non-anticoagulated individuals with and without AF. METHODS: A total of 1 118 762 individuals including 34 460 AF patients were followed during 2011-18 until ischaemic stroke, intracranial haemorrhage, increased CHA2DS2-VASc score, or study end. One-year incidence rates (IRs) were calculated as events per 100 person-years (%/py). Cox regression models provided adjusted hazard ratios (aHRs [95% confidence intervals]). RESULTS: Among AF patients, the ischaemic stroke IR was 0.51%/py in OAC users and 1.05%/py in non-users (aHR 0.47 [0.37-0.59]). Intracranial haemorrhage IR was 0.28%/py in OAC users and 0.19%/py in non-users (aHR 1.23 [0.88-1.72]). Oral anticoagulant use was associated with an increased risk of major bleeding (aHR 1.37 [1.16-1.63]) but lower risk of the combined outcome of ischaemic stroke, major bleeding, and mortality (aHR 0.57 [0.51-0.63]). Non-anticoagulated individuals with AF had higher risk of ischaemic stroke compared to non-AF individuals with the same risk profile (aHR 2.47 [2.17-2.81]). CONCLUSIONS: In AF patients at intermediate risk of stroke, OAC use was associated with overall favourable clinical outcomes. Non-anticoagulated AF patients had higher risk of ischaemic stroke compared to the general population without AF with the same risk profile.

Endovascular therapy versus best medical management for isolated posterior cerebral artery occlusion: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Isolated posterior cerebral artery occlusions (iPCAO) were underrepresented in pivotal randomized clinical trial (RCTs) of endovascular thrombectomy (EVT) in ischemic stroke, and the benefit of EVT in this population is still indeterminate. We performed a systematic review and a meta-analysis to compare the safety and efficacy of EVT compared to best medical management (BMM) in patients with iPCAO. METHODS: We searched Medline/PubMed, Embase, Web of Science, and the Cochrane databases up to May 2023 for eligible studies reporting outcomes of patients with iPCAO treated with EVT or BMM. We pooled odds ratios (ORs) with corresponding 95% confidence intervals (CI) using a random-effects model. RESULTS: Seven studies involving 2560 patients were included. EVT was associated with significantly higher likelihood of early neurological improvement (OR, 2.31 [95% CI, 1.38-2.91]; p < 0.00001) and visual field normalization (OR, 3.08 [95% CI, 1.76-5.38]; p < 0.0001) compared to BMM. Rates of good functional outcomes (mRS 0-2) were comparable between the two arms (OR, 0.88 [95% CI, 0.70-1.10]; p = 0.26). Symptomatic intracranial hemorrhage (sICH) was comparable between the two groups (OR, 1.94 [95% CI, 0.96-3.93]; p = 0.07). Mortality was also similar between the two groups (OR, 1.36; [95% CI, 0.77-2.42]; p = 0.29). CONCLUSIONS: In patients with iPCAO, EVT was associated with visual and early neurological improvement but with a strong trend toward increased sICH. Survival and functional outcomes may be slightly poorer. The role of EVT in iPCAO remains uncertain.

Perioperative Low-Dose Aspirin Management for Planned Clipping Surgery: When, How Long, and With What Precautions?

BACKGROUND AND OBJECTIVE: Perioperative low-dose aspirin (ASA) management for open craniotomy surgery lacked information. We analyze to establish the perioperative ASA strategy to minimize both hemorrhagic and thromboembolic complications. METHODS: The investigators designed a multicenter retrospective study, which included patients scheduled to have clipping surgery for unruptured intracranial aneurysm. The incidence and risk factors were analyzed for postoperative hemorrhagic complications and major cardio- and cerebrovascular events (MACCEs) within 1 month postoperation. RESULTS: This study included 503 long-term ASA users of 3654 patients at three tertiary centers. The incidence of hemorrhagic complications and MACCEs was 7.4% (37/503) and 8.8% (44/503), respectively. Older age (>70 years, odds ratio [OR]: 2.928, 95% CI [1.337-6.416]), multiple aneurysms operation (OR: 2.201, 95% CI [1.017-4.765]), large aneurysm (>10 mm, OR: 4.483, 95% CI [1.485-13.533]), and ASA continuation (OR: 2.604, 95% CI [1.222-5.545]) were independent risk factors for postoperative hemorrhagic complications. Intracranial hemorrhage was the only type of hemorrhagic complication that increased in the ASA continuation group (10.6% vs 2.9%, P = .001). Between the ASA continuation and discontinuation groups, the overall incidence of MACCEs was not significantly different (log-rank P = .8). In the subgroup analysis, ASA discontinuation significantly increased the risk of MACCEs in the secondary prevention group (adjusted hazard ratio: 2.580, 95% CI [1.015-6.580]). CONCLUSION: ASA continuation increased the risk of postoperative intracranial hemorrhage. Simultaneously, ASA discontinuation was the major risk factor for postoperative MACCEs in the high-risk group. Without evidence of intracranial hemorrhage, early ASA resumption was indicated (a total cessation duration <7-10 days) in the secondary prevention group.

Cerebral Small Vessel Disease Burden for Bleeding Risk during Antithrombotic Therapy: Bleeding with Antithrombotic Therapy 2 Study.

OBJECTIVE: This study was undertaken to determine the excess risk of antithrombotic-related bleeding due to cerebral small vessel disease (SVD) burden. METHODS: In this observational, prospective cohort study, patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were enrolled from 52 hospitals across Japan between 2016 and 2019. Baseline multimodal magnetic resonance imaging acquired under prespecified conditions was assessed by a central diagnostic radiology committee to calculate total SVD score. The primary outcome was major bleeding. Secondary outcomes included bleeding at each site and ischemic events. RESULTS: Of the analyzed 5,250 patients (1,736 women; median age = 73 years, 9,933 patient-years of follow-up), antiplatelets and anticoagulants were administered at baseline in 3,948 and 1,565, respectively. Median SVD score was 2 (interquartile range = 1-3). Incidence rate of major bleeding was 0.39 (per 100 patinet-years) in score 0, 0.56 in score 1, 0.91 in score 2, 1.35 in score 3, and 2.24 in score 4 (adjusted hazard ratio [aHR] for score 4 vs 0 = 5.47, 95% confidence interval [CI] = 2.26-13.23), that of intracranial hemorrhage was 0.11, 0.33, 0.58, 0.99, and 1.06, respectively (aHR = 9.29, 95% CI = 1.99-43.35), and that of ischemic event was 1.82, 2.27, 3.04, 3.91, and 4.07, respectively (aHR = 1.76, 95% CI = 1.08-2.86). In addition, extracranial major bleeding (aHR = 3.43, 95% CI = 1.13-10.38) and gastrointestinal bleeding (aHR = 2.54, 95% CI = 1.02-6.35) significantly increased in SVD score 4 compared to score 0. INTERPRETATION: Total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting the broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy. ANN NEUROL 2024;95:774-787.

Chronic kidney disease prevalence and clinical outcomes in anterior circulation acute ischemic stroke patients with reperfusion therapy: A meta-analysis.

AIM: Chronic Kidney Disease (CKD) is a common comorbidity among acute ischaemic stroke (AIS) patients undergoing reperfusion therapies, including intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT). Acknowledging CKD's prevalence in this cohort and understanding its influence on outcomes is crucial for prognosis and optimizing care. This study aims to determine the prevalence of CKD among anterior circulation AIS (acAIS) patients undergoing reperfusion therapies and to analyse the role of CKD in mediating outcomes. METHODS: A random-effects meta-analysis was conducted to pool and examine prevalence data. A total of 263 633 patients were included in the meta-analysis. The study assessed CKD's association with functional outcomes, symptomatic intracranial haemorrhage (sICH) and mortality. RESULTS: The overall pooled prevalence of CKD among acAIS ranged from 30% to 56% in IVT-treated patients and 16%-42% for EVT-treated patients. CKD was associated with increased odds of unfavourable functional outcome at 90 days in both IVT (OR 1.837; 95% CI: [1.599; 2.110]; p < .001) and EVT (OR 1.804; 95% CI: [1.525; 2.133]; p < .001) groups. In IVT-treated patients, CKD was associated with increased odds of 30-day mortality (OR 6.211; 95% CI: [1.105; 34.909]; p = .038). CKD in IVT-treated patients exhibited increased odds of sICH, albeit statistically non-significant (OR 1.595; 95% CI: [0.567; 3.275]). CONCLUSIONS: The high prevalence of CKD and its significant impact on outcomes in acAIS patients treated with reperfusion therapies underscore its clinical significance. This insight can guide personalised care strategies and potentially improve the prognosis in the management of acAIS.

Atrial Fibrillation and Clinical Outcomes of Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-Analysis of Adjusted Effect Estimates.

BACKGROUND: The impact of atrial fibrillation (AF) on the clinical outcomes in patients with acute ischemic stroke (AIS) who received endovascular thrombectomy remains unclear. We aimed to perform a meta-analysis of adjusted effect estimates to examine the association between the presence of AF and the clinical outcomes in patients with AIS who received endovascular thrombectomy. METHODS AND RESULTS: We searched PubMed, Embase, and the Cochrane database between January 1, 2013 and July 10, 2023. Data were meta-analyzed to compare the outcomes among patients with AIS with and without AF who received endovascular thrombectomy. Our primary outcome was 90-day functional independence defined as a modified Rankin Scale score of 0 to 2. Secondary outcomes included excellent independence (90-day modified Rankin Scale score of 0-1), 90-day mortality, symptomatic intracranial hemorrhage, and any intracranial hemorrhage. Eighteen observational studies comprising 16 096 patients with AIS (mean age, 70.1 years; women, 48.2%; 6862 with AF versus 9234 without AF) were included. There were no statistically significant differences for modified Rankin Scale score of 0 to 2 (pooled odds ratio [OR], 1.14 [95% CI, 0.95-1.37]; [95% prediction interval [PI], 0.72-1.80]), mortality (OR, 0.92 [95% CI, 0.79-1.08]; [95% PI, 0.77-1.11]), symptomatic intracranial hemorrhage (OR, 0.97 [95% CI, 0.71-1.32]; [95% PI, 0.43-2.17]), and any intracranial hemorrhage (OR, 1.08 [95% CI, 0.91-1.28]; [95% PI, 0.74-1.58]) among patients with AIS with and without AF. CONCLUSIONS: This meta-analysis detected no significant differences in 90-day functional outcomes, mortality, and intracerebral hemorrhage risk after endovascular thrombectomy in patients with AIS with and without AF. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD 42021293511.

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients With Recent Direct Oral Anticoagulant Use: A Systematic Review and Meta-Analysis.

BACKGROUND: Intravenous thrombolysis (IVT) is an effective stroke therapy that remains underused. Currently, the use of IVT in patients with recent direct oral anticoagulant (DOAC) intake is not recommended. In this study we aim to investigate the safety and efficacy of IVT in patients with acute ischemic stroke and recent DOAC use. METHODS AND RESULTS: A systematic review and meta-analysis of proportions evaluating IVT with recent DOAC use was conducted. Outcomes included symptomatic intracranial hemorrhage, any intracranial hemorrhage, serious systemic bleeding, and 90-day functional independence (modified Rankin scale score 0-2). Additionally, rates were compared between patients receiving IVT using DOAC and non-DOAC by a random effect meta-analysis to calculate pooled odds ratios (OR) for each outcome. Finally, sensitivity analysis for idarucizumab, National Institutes of Health Stroke Scale, and timing of DOAC administration was completed. Fourteen studies with 247 079 patients were included (3610 in DOAC and 243 469 in non-DOAC). The rates of IVT complications in the DOAC group were 3% (95% CI, 3-4) symptomatic intracranial hemorrhage, 12% (95% CI, 7-19) any ICH, and 0.7% (95%CI, 0-1) serious systemic bleeding, and 90-day functional independence was achieved in 57% (95% CI, 43-70). The rates of symptomatic intracranial hemorrhage (3.4 versus 3.5%; OR, 0.95 [95% CI, 0.67-1.36]), any intracranial hemorrhage (17.7 versus 17.3%; OR, 1.23 [95% CI, 0.61-2.48]), serious systemic bleeding (0.7 versus 0.6%; OR, 1.27 [95% CI, 0.79-2.02]), and 90-day modified Rankin scale score 0-2 (46.4 versus 56.8%; OR, 1.21 [95% CI, 0.400-3.67]) did not differ between DOAC and non-DOAC groups. There was no difference in symptomatic intracranial hemorrhage rate based on idarucizumab administration. CONCLUSIONS: Patients with acute ischemic stroke treated with IVT in recent DOAC versus non-DOAC use have similar rates of hemorrhagic complications and functional independence. Further prospective randomized trials are warranted.

Meta-analysis of outcomes following intravenous thrombolysis in patients with ischemic stroke on direct oral anticoagulants.

BACKGROUND: There has been debate on the use of intravenous thrombolysis (IVT) in patients with ischemic stroke and the recent use of direct oral anticoagulants (DOACs). Studies have compared these patients with non-DOAC groups in terms of outcomes. Herein, we aimed to systematically investigate the association between DOAC use and IVT's efficacy and safety outcomes. RESULTS: A comprehensive systematic search was performed in PubMed, Embase, Scopus, and the Web of Science for the identification of relevant studies. After screening and data extraction, a random-effect meta-analysis was performed to calculate the odds ratio (OR) and 95% confidence interval (CI) for comparison of outcomes between patients on DOAC and controls. Six studies were included in the final review. They investigated a total of 254,742 patients, among which 3,499 had recent use of DOACs. The most commonly used DOACs were rivaroxaban and apixaban. The patients on DOAC had significantly higher rates of atrial fibrillation, hypertension, diabetes, and smoking. Good functional outcome defined by modified Rankin Scale (mRS) 0-2 was significantly lower in patients who received DOACs (OR 0.71, 95% CI 0.62 to 0.81, P < 0.01). However, in the subgroup analysis of 90-day mRS 0-2, there was no significant difference between groups (OR 0.71, 95% 0.46 to 1.11, P = 0.14). All-cause mortality was not different between the groups (OR 1.02, 95% CI 0.68 to 1.52, P = 0.93). Similarly, there was no significant difference in either of the in-hospital and 90-day mortality subgroups. Regarding symptomatic intracranial hemorrhage (sICH), the previous DOAC use was not associated with an increased risk of bleeding (OR 0.98, 95% CI 0.69 to 1.39, P = 0.92). A similar finding was observed for the meta-analysis of any ICH (OR 1.15, 95% CI 0.94 to 1.40, P = 0.18). CONCLUSIONS: Based on our findings, IVT could be considered as a treatment option in ischemic stroke patients with recent use of DOACs since it was not associated with an increased risk of sICH, as suggested by earlier studies. Further larger studies are needed to confirm these findings and establish the safety of IVT in patients on DOAC.

Predictors of intracranial hemorrhage in neonatal patients on extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a life-supportive treatment in neonatal patients with refractory lung and/or heart failure. Intracranial hemorrhage (ICH) is a severe complication and reliable predictors are warranted. The aims of this study were to explore the incidence and possible predictors of ICH in ECMO-treated neonatal patients. We performed a single-center retrospective observational cohort study. Patients aged ≤ 28 days treated with ECMO between 2010 and 2018 were included. Exclusion criteria were ICH, ischemic stroke, cerebrovascular malformation before ECMO initiation or detected within 12 h of admission, ECMO treatment < 12 h, or prior treatment with ECMO at another facility > 12 h. The primary outcome was a CT-verified ICH. Logistic regression models were employed to identify possible predictors of the primary outcome. Of the 223 patients included, 29 (13%) developed an ICH during ECMO treatment. Thirty-day mortality was 59% in the ICH group and 16% in the non-ICH group (p < 0.0001). Lower gestational age (p < 0.01, odds ratio (OR) 0.96; 95%CI 0.94-0.98), and higher pre-ECMO lactate levels (p = 0.017, OR 1.1; 95%CI 1.01-1.18) were independently associated with increased risk of ICH-development. In the clinical setting, identification of risk factors and multimodal neuromonitoring could help initiate steps that lower the risk of ICH in these patients.

Efficacy and Safety of Direct Oral Anticoagulants for Stroke Prevention in Older Patients With Atrial Fibrillation: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Although older patients with atrial fibrillation are at heightened risk of thromboembolic and bleeding events, their optimal treatment choice remains uncertain. METHODS AND RESULTS: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that compared thromboembolic or bleeding outcomes between a direct oral anticoagulant (DOAC) and a vitamin K antagonist (VKA) and reported outcomes for patients aged ≥75 years with atrial fibrillation. The efficacy outcome was the composite of stroke and systemic embolism. Safety outcomes included major bleeding, any clinically relevant bleeding, and intracranial hemorrhage. Each DOAC and VKA was compared pairwise in a network meta-analysis. High- and low-dose regimens and factor IIa and Xa inhibitors were also compared. Seven randomized controlled trials were included in the analysis. Stroke and systemic embolism risks did not differ significantly among DOACs. There were no significant differences in major bleeding between each DOAC and VKA. Intracranial hemorrhage risk was significantly lower with dabigatran, apixaban, and edoxaban than with VKA and rivaroxaban, which had similar risks. High-dose regimens led to lower risks of stroke or systemic embolism compared with VKA and low-dose regimens, with both doses having similar bleeding risks. CONCLUSIONS: In patients aged ≥75 years with atrial fibrillation, DOACs were associated with fewer thromboembolic events compared with VKA, whereas dabigatran, apixaban, and edoxaban were associated with lower risks of intracranial hemorrhage compared with VKA and rivaroxaban. REGISTRATION: URL: www.crd.york.ac.uk/prospero/. Unique identifier: CRD42022329557.