Risk Of Recurrent Ischemic Stroke Research Articles

Abstract 17841: Early versus Late Anticoagulation for Ischemic Stroke Associated With Atrial Fibrillation: An Updated Systematic Review and Meta-Analysis

Introduction: The optimal timing for initiating oral anticoagulation in patients who have experienced ischemic stroke is debatable. We conducted an updated systematic review and meta-analysis on the outcomes of patients who received early oral anticoagulation (within <4 days) compared to those who received late oral anticoagulation (within 4-10 days) following the onset of ischemic stroke. Methods: We conducted a systematic literature search according to PRISMA guidelines to identify studies using the terms: “timing of anticoagulation,” “oral anticoagulants,” and “ischemic stroke.” After the screening, We extracted the data from 1980 to May 2023 in a data extraction sheet. We extracted data for three outcomes: Recurrent Ischemic Stroke (IS), Symptomatic Intracranial Hemorrhage (ICH), and all-cause mortality. We used a variance-weighted random-effects model to analyze early vs. late anticoagulation data, estimating event rates and odds ratios while assessing heterogeneity. Data were analyzed using RevMan software. Results: Our analysis included a total of 08 studies (n= 8119 patients). Early anticoagulation (<4 days) was associated with a lower risk of recurrent ischemic stroke, OR= 0.77(95% CI: 0.60- 0.99, I 2 = 21% ) as compared to late anticoagulation (4-10 days). However, there was no significant difference between the timing for symptomatic ICH, OR=1.27 (95% CI: 0.35- 4.64, I 2 = 0% ). Early anticoagulation was also associated with a reduction in all-cause mortality between the two patient groups. OR=0.63(95% CI: 0.43- 0.93, I 2 = 38% ).(Figure1) Conclusions: Early anticoagulation therapy may significantly reduce the recurrence of ischemic stroke and overall mortality with no significant impact on the risk of symptomatic ICH. More randomized control trials are needed to increase the robustness and reliability of these results.

Abstract 17189: Association Between an Artificial Intelligence-Enabled ECG Algorithm for Detection of Atrial Fibrillation While in Sinus Rhythm, and Hospitalization for Recurrent Ischemic Stroke in the Community

Introduction: Artificial Intelligence-enabled electrocardiogram (AI-ECG) can estimate the probability of having atrial fibrillation (AFib) while in sinus rhythm. Recurrent stroke in subjects without known AFib may be due to undiagnosed AFib. We evaluated the association between AI-ECG AFib and recurrent ischemic stroke and with incident AFib Methods: Consecutive adults admitted to a Mayo Clinic or Mayo Clinic Health System hospital or to Olmsted Community Hospital for ischemic stroke between January,1,2000 and June,30,2022 were identified using the Rochester Epidemiology Project. Recurrent ischemic strokes were identified after reviewing medical records and imaging studies. We excluded those with known AFib or without ECGs within 3 years prior to the first ischemic stroke. The AI-ECG network was previously developed using 649,931 ECGs from > 180,000 subjects. The primary endpoint was recurrent ischemic stroke; secondary endpoint was incident AFib. Cox model adjusted for age, sex, and CHA2DS2-VASc2 score variables. Results: We included 4,816 subjects, mean age 70±15 yr, 54% male, 92% white, median CHA2DS2-VASc2 score 4 [3-5], median follow-up 3 [1-7] yr. 280 subjects (6%) had a second stroke and 366 (8%) were diagnosed with incident AFib over follow-up. Those with a positive AI-ECG AFib had an increased risk for recurrent ischemic stroke(HR 1.54, 95% CI 1.21-1.96, P<0.001 Figure A) This association remained significant after adjustment for CHA2DS2-VASc2 score(HR 1.37 95% CI 1.07-1.76, P=0.01). These associations were not affected by anticoagulation use over follow-up. AI-ECG AFib was also associated with incident AFib(HR 2.42 95% CI 1.96-2.98, P<0.001 Figure B) Conclusions: AI-ECG AFib predicts recurrent ischemic stroke in the community, possibly reflecting undiagnosed AFib that can be detected by AI-ECG, as it also predicts incident AFib. These results underscore the potential utility of AI-ECG for risk stratification of patients with ischemic stroke.

Comparison of Aspirin and P2Y12 Inhibitors for Secondary Prevention of Ischaemic Stroke: A Systematic Review and Meta-analysis.

P2Y12 inhibitors have been widely used as an alternative to aspirin in clinical practice for secondary stroke prevention. We aimed to compare the efficiency and safety of P2Y12 inhibitors and aspirin for stroke prevention in patients with previous stroke or transient ischaemic attack (TIA). PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched. All randomized trials that compared P2Y12 inhibitors with aspirin among patients with stroke were included. The primary efficacy outcomes of our meta-analysis included stroke, vascular events, and all-cause death. The primary safety outcome was minor or major bleeding events. The search identified 4 randomized clinical trials comparing P2Y12 inhibitors with aspirin for secondary stroke prevention that collectively enrolled 24508 patients (12253 received P2Y12 inhibitor and 12255 received aspirin). Pooled results from the random-effects model showed that there were no significant differences in the risk of any stroke (OR 0.90 (0.78-1.04); I²=56.9%), vascular event (OR 0.91 (0.74-1.13); I²=78.3%), all-cause death (OR 0.98 (0.83-1.17); I²=0%), or minor or major bleeding (OR 1.13 (0.70-1.82); I²=79%) among patients who received a P2Y12 inhibitor or aspirin. P2Y12 inhibitors were associated with a significantly lower risk of recurrent ischaemic stroke (OR 0.84 (0.73- 0.96); I²=25%) than aspirin. This meta-analysis suggests that P2Y12 inhibitors are more effective than aspirin in preventing recurrent ischaemic stroke among ischaemic stroke patients despite the absence of any effect on a new ischaemic or haemorrhagic stroke, a new clinical vascular event, all-cause death, and major or minor bleeding events.

Association of culprit plaque enhancement ratio, hypoperfusion and HbA1c with recurrent ischemic stroke in patients with atherosclerotic stenosis of the middle cerebral artery

PurposeTo investigate the differences in intracranial culprit plaque characteristics of the middle cerebral artery (MCA), collateral circulation and hypoperfusion in patients with and without recurrent ischemic stroke and to identify the association with the recurrent ischemic cerebrovascular events. MethodEighty-six patients with acute/subacute ischemic stroke caused by atherosclerotic plaques of the MCA were retrospectively enrolled and grouped into patients with recurrence (n = 36) and without recurrence (n = 50). All patients underwent high-resolution vessel wall imaging and dynamic susceptibility contrast-enhanced perfusion weighted imaging. The differences in culprit plaque characteristics, collateral circulation and hypoperfusion in the territory of the stenotic MCA were assessed between the two groups. The relationship between plaque characteristics and hypoperfusion was evaluated. The independent factors of recurrent ischemic stroke were identified by logistic regression analyses. ResultsHigher HbA1c, culprit plaque enhancement grade, culprit plaque enhancement ratio, and lower time to peak map based on the Alberta Stroke Program Early CT score (TTP-ASPECTS) were observed in the recurrence group(all p < 0.050). Both plaque enhancement grade and enhancement ratio were significantly associated with TTP-ASPECTS (p = 0.030 and 0.039, respectively). HbA1c, culprit plaque enhancement ratio and TTP-ASPECTS were independent factors of the recurrence of ischemic stroke (all p < 0.050). The area under the curve of the combination including the above factors (AUC = 0.819) was significantly higher than that of any variable alone after adjustment (all p < 0.050). ConclusionsCulprit plaque enhancement ratio, TTP-ASPECTS and HbA1c were independent factors of recurrent ischemic stroke. Their combination improved the accuracy in identifying the risk of recurrent ischemic stroke.

Atrial Fibrillation and Ischemic Stroke despite Oral Anticoagulation.

Patients with atrial fibrillation (AF) experiencing ischemic stroke despite oral anticoagulation (OAC), i.e., breakthrough strokes, are not uncommon, and represent an important clinical subgroup in view of the consistently high risk of stroke recurrence and mortality. The understanding of the heterogenous potential mechanism underlying OAC failure is essential in order to implement specific therapeutic measures aimed at reducing the risk of recurrent ischemic stroke. However, due to the incomplete comprehension of this phenomenon and the limited available data, secondary stroke prevention in such high-risk patients represents a clinical dilemma. There are several available strategies to prevent ischemic stroke recurrence in AF patients with breakthrough stroke in the absence of competing causes unrelated to AF, and these include continuation or change in the type of OAC, addition of antiplatelet therapy, left atrial appendage closure, or any combination of the above options. However, due to the limited available data, the latest guidelines do not provide any specific recommendations about which of the above strategies may be preferred. This review describes the incidence, the clinical impact and the potential mechanisms underlying OAC failure in AF patients. Furthermore, the evidence supporting each of the above therapeutic options for secondary stroke prevention and the potential future directions will be discussed.

Estimating a two-year recurrence risk of ischemic stroke based on Essen Stroke Risk Score and retinal characteristics

Objectives: Prediction of recurrence risk after initial ischemic stroke helps improve patient outcomes. We estimated the validity of combining the Essen Stroke Risk Score (ESRS) with retinal characteristics to predict the two-year recurrent risk of ischemic stroke. Methods: A prospective cohort study was conducted at Shenzhen Traditional Chinese Medicine Hospital. Patients with initial ischemic stroke were recruited. ESRS was measured, and fundus photographs were taken by trained physicians. All patients were followed up for 2 years to determine the outcome of recurrent stroke. Logistic models were built using ESRS alone and combined with ESRS and retinal characteristics. The prognostic value of recurrence risk was evaluated by calculating the area under the receiver operating characteristic curve. Results: The total recurrence rate of ischemic events within 2 years was 20%. The risk of recurrence was significantly higher in patients with an ESRS score of &gt;2. Regarding retinal characteristics, patients with recurrent stroke had a lower mean asymmetry index of venules (0.76 vs. 0.77, P=0.00) and bifurcation coefficient of venules (1.29 vs. 1.28, P=0.03) but a higher mean occlusion of arterioles (0.11 vs. 0.13, P=0.01). The area under the curve was 0.5985 based on the logistic regression model with ESRS alone to 0.7294 for the model with both ESRS and retinal characteristics. This study was registered in the Chinese Clinical Trial Registry (registration no. ChiCTR1800019648). Conclusion: A model combining ESRS with retinal characteristics can accurately predict the risk of recurrent stroke.

Leukoaraiosis as a Promising Biomarker of Stroke Recurrence among Stroke Survivors: A Systematic Review.

Stroke is the leading cause of functional disability worldwide, with increasing prevalence in adults. Given the considerable negative impact on patients' quality of life and the financial burden on their families and society, it is essential to provide stroke survivors with a timely and reliable prognosis of stroke recurrence. Leukoaraiosis (LA) is a common neuroimaging feature of cerebral small-vessel disease. By researching the literature of two different databases (MEDLINE and Scopus), the present study aims to review all relevant studies from the last decade, dealing with the clinical utility of pre-existing LA as a prognostic factor for stroke recurrence in stroke survivors. Nineteen full-text articles published in English were identified and included in the present review, with data collected from a total of 34,546 stroke patients. A higher rate of extended LA was strongly associated with stroke recurrence in all stroke subtypes, even after adjustment for clinical risk factors. In particular, patients with ischemic stroke or transient ischemic attack with advanced LA had a significantly higher risk of future ischemic stroke, whereas patients with previous intracerebral hemorrhage and severe LA had a more than 2.5-fold increased risk of recurrent ischemic stroke and a more than 30-fold increased risk of hemorrhagic stroke. Finally, in patients receiving anticoagulant treatment for AF, the presence of LA was associated with an increased risk of recurrent ischemic stroke and intracranial hemorrhage. Because of this valuable predictive information, evaluating LA could significantly expand our knowledge of stroke patients and thereby improve overall stroke care.

Ticagrelor plus aspirin in patients with minor ischemic stroke and transient ischemic attack: a network meta-analysis

BackgroundDual antiplatelet therapy (DAPT) with aspirin and clopidogrel was recommended as the secondary prevention of minor ischemic stroke or transient ischaemic attack (TIA). However, genetic polymorphisms of CYP2C19 had been identified as the major cause of poor responsiveness to clopidogrel. Ticagrelor, unlike clopidogrel, did not depend on metabolic activation, but it remained unclear whether ticagrelor was superior to clopidogrel in ischemic stroke. We performed a network meta-analysis to compare the efficacy and safety of ticagrelor, clopidogrel, and aspirin in the minor ischemic stroke and TIA populations.MethodsDatabases of Cochrane Library, ClinicalTrials.gov, and PubMed were searched up to June 19, 2023. Randomized controlled trials (RCTs) assessing antiplatelet drugs for minor stroke or TIA were included. Statistical processing was conducted by using multivariate meta-analysis routines of STATA.ResultsSeven RCTs were included involving 41,745 participants. There was no significant difference between the two DAPTs in preventing stroke recurrence (OR, 1.16; 95% CI, 0.93-1.44), ischemic stroke recurrence (OR, 1.16; 95% CI, 0.93-1.45), and major hemorrhage (OR, 1.22; 95% CI, 0.62,2.39). Compared with aspirin alone, the two DAPT regimen reduced the risk of stroke recurrence (clopidogrel: OR, 0.69; 95% CI, 0.60-0.80, ticagrelor: OR, 0.66; 95% CI, 0.49-0.87) and ischemic stroke recurrence, but increased the incidence of major hemorrhage (clopidogrel: OR, 2.05; 95% CI, 1.22- 3.77; ticagrelor: OR, 2.55; 95% CI, 1.25-4.99). Despite being associated with a higher risk of any bleeding, ticagrelor did not impact the composite of vascular events or mortality. While ticagrelor and aspirin reduced the risk of ischemic stroke recurrence (OR, 0.77; 95% CI, 0.63- 0.92) without increasing the risk of major bleeding (OR 0.94; 95% CI 0.45–1.95) in the Asian population mainly Chinese.ConclusionsDAPT was superior to aspirin in stroke prevention, but little difference existed between the two DAPT regimens. Asian population mainly Chinese may benefit from DAPT with aspirin and ticagrelor. But further head-to-head RCTs are needed to validate the study results.

Correlation of the middle cerebral artery atherosclerotic plaque characteristics with ischemic stroke recurrence: a vessel wall magnetic resonance imaging study.

This study aims to analyze the imaging features of atherosclerotic plaques in the middle cerebral artery (MCA) of patients with recurrent ischemic stroke using vessel wall magnetic resonance imaging (VWMRI) and investigate the correlation between these imaging features and the recurrence of ischemic stroke. Consecutive patients with ischemic stroke caused by atherosclerotic stenosis of the MCA were collected. The patients were divided into recurrent and non-recurrent ischemic stroke groups. We obtained VWMRI images of MCA plaques using 3.0T MRI by black-blood sequences, and the differences in VWMRI characteristics and clinical information between the two groups were compared. A binary Logistic regression model was used to analyze the VWMRI characteristics and clinical information related to ischemic stroke recurrence. 179 patients were collected from August 2018 to May 2020, and 81 patients were included in the study. The recurrent ischemic stroke group patients had a higher stenosis rate (0.69 vs 0.64). Meanwhile, the rate of centripetal wall thickening was significantly higher in patients with recurrent ischemic stroke (33.3% vs 11.7%). Binary Logistic regression analysis showed that sex (P=0.036, OR:2.983, CI:1.075-8.279), stenosis rate (P=0.038, OR:148.565, CI:1.331-16583.631), and vessel wall thickening pattern (P=0.012, OR:0.171, CI:0.043-0.678) were related to ischemic stroke recurrence. The patients with ischemic stroke caused by atherosclerotic stenosis of MCA, female patients, and those with concentric wall thickening and a high degree of stenosis have a higher risk of recurrence. Our results suggest that VWMRI is a valuable tool for predicting the risk of ischemic stroke recurrence in patients with MCA plaques.

Validation and comparison of the stroke prognosis instrument (SPI-II) and the essen stroke risk score (ESRS) in predicting stroke recurrence in Asian population

BackgroundCurrently, there are limited data on the accuracy of available risk scores to predict stroke recurrence in the Asian population.MethodA single-center, retrospective cohort study was conducted among patients with acute ischemic stroke during January 2014 - December 2018. Longitudinal data with three years of follow-up among these patients were collected and validated through both electronic and manual chart review. The area under the receiver-operating curve (AUROC) method or C-statistic and calibration plot were used to evaluate and compare the Stroke Prognosis Instrument II (SPI-II) and the Essen Stroke Risk Score (ESRS) in predicting the long-term risk of recurrent ischemic stroke. The predictive performances of the two scores were compared using DeLong’s method.ResultsThe study cohort consisted of 543 patients, including 181 and 362 patients with and without recurrent events. There were no significant differences in mean age and gender between the two groups. Recurrence cases tended to have significant more risk factors compared to those without events. Among cases with recurrent events, 134 (74.03%) and 65.74% (119) cases were classified as high-risk based on SPI-II and ESRS, respectively. The AUROC curve of the SPI-II and ESRS score was 0.646 (95% CI, 0.594–0.697) and 0.614 (95%CI, 0.563–0.665), respectively (p = 0.394). Based on the calibration plot, the SPI-II and ESRS scores showed similar moderate predictive performance on recurrence stroke with a C statistic (95% CI) of 0.655 (95% CI: 0.603–0.707) and 0.631 (95% CI 0.579–0.684), respectively.ConclusionBoth ESRS and SPI-II scores had moderate predictive performance in Thai population.

Risk of recurrent ischemic stroke in patients with patent foramen ovale: The role of D-dimer

BackgroundParadoxical embolism under elevated thromboembolic conditions is known to be the primary mechanism of patent foramen ovale (PFO)-related stroke. We hypothesized that higher levels of D-dimer, a marker of thromboembolism, could increase the risk of stroke recurrence in patients with PFO. MethodsWe conducted a retrospective analysis of data from 1226 consecutive patients with acute ischemic cryptogenic stroke (CS) who underwent transesophageal echocardiography (TEE). D-dimer was assessed during admission. We used a multivariate Cox proportional hazards model to evaluate the association of long-term outcomes between the presence of PFO and levels of D-dimer. ResultsOf the 1226 patients, the study included 461 who underwent TEE. Among them, 242 (52.5%) had PFOs. Among PFO patients, those with a D-dimer level >1.0 mg/L had a significantly higher risk of stroke recurrence compared to those with <0.5mg/L (adjusted hazard ratio (aHR) 4.04, 95% confidence interval [CI] 1.63–10.02). A pattern of increased risk of event with increasing D-dimer levels was observed (Ptrend=0.008). However, there was no significant difference in the risk of stroke recurrence at any D-dimer level compared to D-dimer level <0.5 mg/L among patients without PFO. In these patients, there was little evidence of increased risk with increasing D-dimer levels (Ptrend=0.570). ConclusionsThis study demonstrated that the elevated D-dimer level increased the recurrence of stroke in CS patients with PFO, particularly showing a dose-dependent relationship between D-dimer levels and recurrence. However, no such effect was observed in patients without PFO. These findings provide valuable insights into the potential benefits of anticoagulation for strokes related to PFO.

Genetic variation supports a causal role for valproate in prevention of ischemic stroke.

Valproate is a candidate for ischemic stroke prevention due to its anti-atherosclerotic effects in vivo. Although valproate use is associated with decreased ischemic stroke risk in observational studies, confounding by indication precludes causal conclusions. We applied Mendelian randomization to determine whether genetic variants that influence seizure response among valproate users associate with ischemic stroke. We derived a genetic score for valproate response using genome-wide association data of seizure response after valproate intake from the Epilepsy Pharmacogenomics Consortium. We then tested this score among valproate users of the UK Biobank for association with incident and recurrent ischemic stroke using Cox proportional hazard models. As replication, we tested found associations in an independent cohort of valproate users of the Mass General Brigham Biobank. Among 2150 valproate users (mean 56 years, 54% females), 82 ischemic strokes occurred over a mean 12 year follow-up. Higher valproate response genetic score was associated with higher serum valproate levels (+5.78 µg/ml per 1 standard deviation (SD), 95% confidence interval (CI) (3.45, 8.11)). After adjusting for age and sex, higher valproate response genetic score was associated with lower ischemic stroke risk (hazard ratio (HR) per 1 SD 0.73, 95% CI (0.58, 0.91)) with a halving of absolute risk in the highest compared to the lowest score tertile (4.8% vs 2.5%, p trend = 0.027). Among 194 valproate users with prevalent stroke at baseline, a higher valproate response genetic score was associated with lower recurrent ischemic stroke risk (HR per 1 SD 0.53, 95% CI (0.32, 0.86)) with reduced absolute risk in the highest compared to the lowest score tertile (3/51, 5.9% vs 13/71, 18.3%, p trend = 0.026). The valproate response genetic score was not associated with ischemic stroke among the 427,997 valproate non-users (p = 0.61), suggesting minimal pleiotropy. In 1241 valproate users of the Mass General Brigham Biobank with 99 ischemic stroke events over 6.5 years follow-up, we replicated our observed associations between the valproate response genetic score and ischemic stroke (HR per 1 SD 0.77, 95% CI (0.61, 0.97)). These results demonstrate that a genetically predicted favorable seizure response to valproate is associated with higher serum valproate levels and reduced ischemic stroke risk among valproate users, providing causal support for valproate effectiveness in ischemic stroke prevention. The strongest effect was found for recurrent ischemic stroke, suggesting potential dual-use benefits of valproate for post-stroke epilepsy. Clinical trials will be required in order to identify populations that may benefit most from valproate for stroke prevention. UK Biobank participant data are available after approval of a research proposal. The weights of the used genetic scores are available in the Supplemental Tables.

Differences in Stroke Recurrence Risk Between Atrial Fibrillation Detected on ECG and 14-Day Cardiac Monitoring.

Ischemic stroke and transient ischemic attack (TIA) standard-of-care etiological investigations include an ECG and prolonged cardiac monitoring (PCM). Atrial fibrillation (AF) detected after stroke has been generally considered a single entity, regardless of how it is diagnosed. We hypothesized that ECG-detected AF is associated with a higher risk of stroke recurrence than AF detected on 14-day Holter (PCM-detected AF). We conducted a retrospective, registry-based, cohort study of consecutive patients with ischemic stroke and TIA included in the London Ontario Stroke Registry between 2018 and 2020, with ECG-detected and PCM-detected AF lasting ≥30 seconds. We quantified PCM-detected AF burden. The primary outcome was recurrent ischemic stroke, ascertained by systematically reviewing all medical records until November 2022. We applied marginal cause-specific Cox proportional hazards models adjusted for qualifying event type (ischemic stroke versus TIA), CHA₂DS₂-VASc score, anticoagulation, left ventricular ejection fraction, left atrial size, and high-sensitivity troponin T to estimate adjusted hazard ratios for recurrent ischemic stroke. We included 366 patients with ischemic stroke and TIA with AF, 218 ECG-detected, and 148 PCM-detected. Median PCM duration was 12 (interquartile range, 8.8-14.0) days. Median PCM-detected AF duration was 5.2 (interquartile range, 0.3-33.0) hours, with a burden (total AF duration/total net monitoring duration) of 2.23% (interquartile range, 0.13%-12.25%). Anticoagulation rate at the end of follow-up or at the first event was 83.1%. After a median follow-up of 17 (interquartile range, 5-34) months, recurrent ischemic strokes occurred in 16 patients with ECG-detected AF (13 on anticoagulants) and 2 with PCM-detected AF (both on anticoagulants). Recurrent ischemic stroke rates for ECG-detected and PCM-detected AF groups were 4.05 and 0.72 per 100 patient-years (adjusted hazard ratio, 5.06 [95% CI, 1.13-22.7]; P=0.034). ECG-detected AF was associated with 5-fold higher adjusted recurrent ischemic stroke risk than PCM-detected AF in a cohort of ischemic stroke and TIA with >80% anticoagulation rate.

Association between post-stroke smoking and stroke recurrence in first-ever ischemic stroke survivors: based on a 10-year prospective cohort.

Whether smoking is a risk factor for ischemic stroke (IS) recurrence in IS survivors is still uncovered, and evidences are sparse. Meanwhile, an add-on effect of clopidogrel was observed in myocardial infarction patients who smoked, but whether the paradox exists in IS patients is still unsolved. The objectives of this study are to explore the association between smoking behavior after index stroke and IS recurrence and to explore whether the paradox exists. A prospective cohort of first-ever IS patients was conducted between 2010 and 2019. The prognosis and smoking features of enrolled patients were obtained via telephone follow-up every 3 months. Fine-gray model with interaction terms was applied to measure the relationships between stroke recurrence and smoking behaviors after index stroke and to explore the add-on effect of clopidogrel in smoking patients. There were 171 (24.26%) recurrences and 129 (18.30%) deaths during follow-up in 705 enrolled IS patients. One hundred forty-six (20.71%) patients smoked after index stroke. The hazard ratios (HRs) and 95% confidence intervals (CIs) of interaction terms between antiplatelet drug and follow-up smoking (smoking status and daily smoking amount) were 1.092 (95% CI: 0.524, 2.276) and 0.985 (95% CI: 0.941, 1.031), respectively. A significantly higher risk of recurrence was observed in patients with a higher daily smoking amount during follow-up (per cigarette), with HR being 1.027 (95% CI: 1.003, 1.052). Smoking could elevate the risk of IS recurrence, and IS survivor should be advised to quit or smoke less. Add-on effect of clopidogrel may not exist in smoking strokers taking clopidogrel.

Elevated hs-CRP and Symptomatic Intracranial/Extracranial Artery Stenosis Predict Stroke Recurrence after Acute Ischemic Stroke or TIA.

This study aimed to investigate the relationship between symptomatic or asymptomatic intracranial/extracranial artery stenosis and high-sensitivity C-reactive protein (hs-CRP) levels in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). This study included 10404 patients from the Third China National Stroke Registry. Patients were divided into four or six groups according to patterns of intracranial or extracranial artery stenosis and hs-CRP levels. The outcomes were recurrence of ischemic stroke, stroke, and combined vascular events (CVE) at 1 year. The associations between different combinations of hsCRP levels and patterns of artery stenosis and recurrent events were analyzed by multivariable Cox regression models. Patients in Group III (hs-CRP ＜3＋symptomatic intracranial or extracranial artery stenosis) had higher risk of recurrent ischemic stroke (adjusted hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.20-2.48,p=0.003). Those in Group VI (hs-CRP ≥ 3＋symptomatic intracranial or extracranial artery stenosis) had the highest risk of recurrent ischemic stroke (HR 2.04, 95% CI 1.42-2.92, p=0.0001) within 1 year compared with Group I (hs-CRP ＜3＋no artery stenosis). Asymptomatic intracranial or extracranial artery stenosis did not increase the risk of ischemic events compared with no artery stenosis regardless of hs-CRP levels. Symptomatic intracranial or extracranial artery stenosis was associated with increased risk of recurrent ischemic stroke, stroke, and CVE at 1 year in patients with AIS or TIA, especially in patients with elevated hs-CRP levels. Asymptomatic intracranial or extracranial artery stenosis did not increase the risk of ischemic events compared with no artery stenosis regardless of hs-CRP levels.

Association of Alternative Anticoagulation Strategies and Outcomes in Patients With Ischemic Stroke While Taking a Direct Oral Anticoagulant.

Ischemic stroke despite a direct oral anticoagulant (DOAC) is increasingly common and portends a high risk of subsequent ischemic stroke. The efficacy and safety of antithrombotic regimens after the condition are unclear. We aimed to compare the outcomes of patients with ischemic stroke despite DOACs with and without an alternative antithrombotic regimen and determine the risk factors of recurrent ischemic stroke while on anticoagulation. In a population-based, propensity score-weighted, retrospective cohort study, we compared the clinical outcomes of DOAC-to-warfarin switch, DOAC-to-DOAC switch (DOACswitch), or addition of antiplatelet agents, with those of unchanged DOAC regimen (DOACsame) among patients with nonvalvular atrial fibrillation (NVAF) who developed the first ischemic stroke despite a DOAC from January 1, 2015, to December 31, 2020, in Hong Kong. The primary outcome was recurrent ischemic stroke. Secondary outcomes were intracranial hemorrhage, acute coronary syndrome, and death. We performed competing risk regression analyses to compare the clinical endpoints and determined the predictors of recurrent ischemic stroke in an unweighted multivariable logistic regression model. During the 6-year study period, among 45,946 patients with AF on a DOAC as stroke prophylaxis, 2,908 patients developed ischemic stroke despite a DOAC. A total of 2,337 patients with NVAF were included in the final analyses. Compared with DOACsame, warfarin (aHR 1.96, 95% CI 1.27-3.02, p = 0.002) and DOACswitch (aHR 1.62, 95% CI 1.25-2.11, p < 0.001) were associated with an increased risk of recurrent ischemic stroke. In the DOACsame group, adjunctive antiplatelet agent was not associated with a reduced risk of recurrent ischemic stroke. Diabetes mellitus, concurrent cytochrome P450/P-glycoprotein (CYP/P-gp) modulators, and large artery atherosclerotic disease (LAD) were predictors of recurrent ischemic stroke. In patients with NVAF with ischemic stroke despite a DOAC, the increased risk of recurrent ischemic stroke with switching to warfarin called for caution against such practice, while the increased ischemic stroke with DOAC-to-DOAC switch demands further studies. Adjunctive antiplatelet agent did not seem to reduce ischemic stroke relapse. Because diabetes mellitus, the use of CYP/P-gp modulators, and LAD were predictors of recurrent ischemic stroke, further investigations should evaluate whether strict glycemic control, DOAC level monitoring, and routine screening for carotid and intracranial atherosclerosis may reduce ischemic stroke recurrence in these patients. This study provides Class II evidence that in patients with NVAF experiencing an ischemic stroke while being treated with a DOAC, continuing treatment with that DOAC is more effective at preventing recurrent ischemic stroke than switching to a different DOAC or to warfarin.

Biliverdin Reductase B Is a Plasma Biomarker for Intraplaque Hemorrhage and a Predictor of Ischemic Stroke in Patients with Symptomatic Carotid Atherosclerosis

Background: Intraplaque hemorrhage (IPH) is a hallmark of atherosclerotic plaque instability. Biliverdin reductase B (BLVRB) is enriched in plasma and plaques from patients with symptomatic carotid atherosclerosis and functionally associated with IPH. Objective: We explored the biomarker potential of plasma BLVRB through (1) its correlation with IPH in carotid plaques assessed by magnetic resonance imaging (MRI), and with recurrent ischemic stroke, and (2) its use for monitoring pharmacotherapy targeting IPH in a preclinical setting. Methods: Plasma BLVRB levels were measured in patients with symptomatic carotid atherosclerosis from the PARISK study (n = 177, 5 year follow-up) with and without IPH as indicated by MRI. Plasma BLVRB levels were also measured in a mouse vein graft model of IPH at baseline and following antiangiogenic therapy targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Results: Plasma BLVRB levels were significantly higher in patients with IPH (737.32 ± 693.21 vs. 520.94 ± 499.43 mean fluorescent intensity (MFI), p = 0.033), but had no association with baseline clinical and biological parameters. Plasma BLVRB levels were also significantly higher in patients who developed recurrent ischemic stroke (1099.34 ± 928.49 vs. 582.07 ± 545.34 MFI, HR = 1.600, CI [1.092–2.344]; p = 0.016). Plasma BLVRB levels were significantly reduced following prevention of IPH by anti-VEGFR-2 therapy in mouse vein grafts (1189 ± 258.73 vs. 1752 ± 366.84 MFI; p = 0.004). Conclusions: Plasma BLVRB was associated with IPH and increased risk of recurrent ischemic stroke in patients with symptomatic low- to moderate-grade carotid stenosis, indicating the capacity to monitor the efficacy of IPH-preventive pharmacotherapy in an animal model. Together, these results suggest the utility of plasma BLVRB as a biomarker for atherosclerotic plaque instability.

In patients who had a stroke or TIA, enlarged perivascular spaces in basal ganglia may cause future haemorrhagic strokes

IntroductionIt remains unclear whether enlarged perivascular spaces (EPVS) predict poor clinical outcomes in patients with acute ischaemic stroke (AIS) or transient ischaemic attack (TIA).MethodData were obtained from the Third China...

A comparison of safety and efficacy between long-term DAPT and intensive statins combined with short-term DAPT for acute ischemic stroke

ObjectivesThe current study compared the safety and efficacy of long-term dual antiplatelet therapy (DAPT, aspirin plus clopidogrel) and intensive rosuvastatin with short-term DAPT for acute ischemic stroke (AIS).MethodsA total of 220 patients were enrolled 72 h after the onset of mild to moderate AIS, and divided into a control group treated with 21-day DAPT and a study group treated with intensive rosuvastatin with 7-day DAPT on a voluntary basis. The primary outcome was recurrent ischemic stroke and hemorrhage during a 90-day follow-up period in an intention-to-treat analysis. The secondary outcome was clinical efficacy with respect to alleviating existing focal nerve defect symptoms. A Cox proportional-hazards model was used to evaluate treatment differences.ResultsClinical efficacy was evident in 87.3% of patients in the study group, compared with 84.3% in the control group (p = 0.042). Recurrent ischemic stroke occurred in 9 patients (7.6%) in the study group and in 9 (8.8%) in the control group (p = 0.767). Hemorrhage occurred in 6 patients (5.1%) in the study group and in 15 (14.7%) in the control group (p = 0.023). In comparisons of levels of ALT, AST, LDH, and CK in the two groups before and 2 weeks after therapy, only CK differed significantly (p < 0.001).ConclusionsCompared to long-term DAPT, intensive rosuvastatin with short-term DAPT was equivalent in reducing the risk of recurrent ischemic stroke. It alleviated symptoms more rapidly, and significantly reduced the risk of bleeding, without causing an increase in transaminase or muscle enzymes.Clinical trial registrationChina Clinical Trial Registration Center (ChiCTR1800017809)

Association between red blood cell distribution width and ischemic stroke recurrence in patients with acute ischemic stroke: a 10-years retrospective cohort analysis

Numerous studies have reported that a higher red blood cell distribution width (RDW) level was associated with adverse outcomes in patients with the first stroke. However, no studies have examined the association between RDW and recurrent ischemic stroke. We performed a population-based cohort data analysis from 2007 to 2017. Baseline RDW was measured in 6402 first ischemic stroke participants, who were followed for about five years on average. During 62 months of median follow-up, 205 participants (3.20%) reported a recurrence (self-reported). RDW showed a nonlinear relationship with the risk of ischemic stroke recurrence. When RDW was assessed as quartiles (quartile 1, RDW<12.4; quartile 2, 12.4 to 12.8; quartile 3,12.8 to 13.3, quartile4, RDW>13.3), compared with the reference group (quartile 1), the hazard ratios (HRs) of ischemic stroke recurrence were 1.372 (95% confidence interval [CI]=0.671-2.805, P=0.386) in quartile 2, 1.835 (95% CI=1.222-2.755, P=0.003) in quartile 3, and 1.732 (95% CI=1.114-2.561, P<0.001) in quartile 4. The trend test was significant (P<0.001). When quartiles 3 and 4 were combined, the adjusted HR of ischemic stroke recurrence was 1.439 (95% CI=1.330-1.556, P<0.001) compared with the combined quartiles 1 and 2 subgroups. This study demonstrated that elevated RDW levels were positively associated with an increased risk of recurrent ischemic stroke. RDW can provide a new perspective for initial risk assessment and identify high-risk patients early. Further research is required to confirm our results.