Incidence Of Recurrent Ischemic Stroke Research Articles

Incidence of recurrent ischemic stroke and its associated factors in a tertiary care center in Thailand: a retrospective cohort study

BackgroundIschemic stroke (IS) is one of the leading causes of death among non-communicable diseases in Thailand. Patients who have survived an IS are at an increased risk of developing recurrent IS, which can result in worse outcomes and post-stroke complications.ObjectivesThe study aimed to investigate the incidence of recurrent IS among patients with first-ever IS during a one-year follow-up period and to determine its associated risk factors.MethodsAdult patients (aged ≥ 18 years) who were hospitalized at the Stroke Center, King Chulalongkorn Memorial Hospital (KCMH) in Bangkok, Thailand, due to first-ever IS between January and December 2019 and had at least one follow-up visit during the one-year follow-up period were included in this retrospective cohort study. IS diagnosis was confirmed by neurologists and imaging. The log-rank test was used to determine the event-free survival probabilities of recurrent IS in each risk factor.ResultsOf 418 patients hospitalized due to first-ever IS in 2019, 366 (87.6%) were included in the analysis. During a total of 327.2 person-years of follow-up, 25 (6.8%) patients developed recurrent IS, accounting for an incidence rate of 7.7 per 100 person-year (95% confidence interval [CI] 5.2–11.3). The median (interquartile range) time of recurrence was 35 (16–73) days. None of the 47 patients with atrial fibrillation developed recurrent IS. The highest incidence rate of recurrent IS occurred within 1 month after the first episode (34 per 100 person-years) compared to other follow-up periods. Patients with small vessel occlusion and large-artery atherosclerosis (LAA) constituted the majority of patients in the recurrent IS episode (48% and 40%, respectively), with LAA exhibiting a higher recurrence rate (13.5%). Additionally, smoking status was found to be associated with an increased risk of recurrence.ConclusionThe incidence rate of the recurrence was moderate in our tertiary care setting, with a decreasing trend over time after the first episode. The various subtypes of IS and smoking status can lead to differences in event-free survival probabilities.

Clopidogrel with indobufen or aspirin in minor ischemic stroke or high-risk transient ischemic attack: a randomized controlled clinical study

BackgroundIschemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases.ObjectiveThe CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA.MethodsAn open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset.ResultsWe enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874–7.036, P < 0.0001). Although the improvement rate of NIHSS score in the indobufen and clopidogrel group was higher than that in the aspirin and clopidogrel group, the difference was not statistically significant (P > 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035).ConclusionThe combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021).

Abstract WP12: Early or Later Anticoagulation in Post-Stroke Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: Uncertainty regarding the timing of anticoagulant initiation after an ischemic stroke in patients with atrial fibrillation arises from the lack of extensive data on this matter. We conducted the first meta-analysis, including only randomized controlled trials, to clarify this question. Methods: We systematically searched Embase, PubMed, and Cochrane Library in June 2023 for studies comparing early versus late initiation of anticoagulation post-stroke in patients with atrial fibrillation. Statistical analyses were performed using R software version 5.4.1. Results: We included three studies comprising 2,989 patients. Of these, 1,497 (50%) received early anticoagulation with a direct oral anticoagulant (DOAC), and 1,492 (50%) received later anticoagulation with a DOAC or warfarin. 51.66% of participants were women. The use of early anticoagulation was associated with a lower incidence of recurrent ischemic stroke; nonetheless, this result lacked statistical significance (RR 0.68; 95% CI 0.44-1.04; p=0.07; I 2 =0%). The number of symptomatic intracerebral hemorrhage events was 2 in the early anticoagulation group and 3 events in the later anticoagulation group, with no statistical significance between the groups. Conclusion: Our findings suggest no statistically significant difference in recurrent ischemic stroke and intracerebral bleeding between the initiation of early or later anticoagulation in post-stroke patients with atrial fibrillation.

Endovascular therapy for acute intracranial large vessel occlusion due to atherothrombosis: Multicenter historical registry

BackgroundAtherothrombotic stroke-related large vessel occlusion (AT-LVO) is caused by two etiologies, the intracranial artery occlusion due to in situ occlusion (intracranial group) or due to embolism from cervical carotid occlusion...

Long-term effectiveness and safety of cilostazol versus clopidogrel in secondary prevention of noncardioembolic ischemic stroke.

Cilostazol is a widely used antiplatelet drug for secondary stroke prevention in Asia, but its comparison with clopidogrel is not well understood. This study aims to investigate the effectiveness and safety of cilostazol compared to clopidogrel for the secondary prevention of noncardioembolic ischemic stroke. This retrospective comparative effectiveness research analyzed 1:1 propensityscorematched data from insured individuals between 2012 and 2019, using administrative claims data in Health Insurance Reviewand Assessment in Korea. Patients with diagnosis codes for ischemic stroke without cardiac disease were included and divided into two groups, those receiving cilostazol and those receiving clopidogrel. The primary outcome was a recurrent ischemic stroke. Secondary outcomes included all-cause death, myocardial infarction, hemorrhagic stroke, and a composite of these outcomes. The safety outcome was major gastrointestinal bleeding. The study analyzed 4,754 patients in the propensityscorematched population and found no statistically significant difference in recurrent ischemic stroke (cilostazol group vs clopidogrel group, 2.7% vs 3.2%; 95% CI, 0.62-1.21), the composite outcome of recurrent ischemic stroke, all-cause death, myocardial infarction, and hemorrhagic stroke (5.1% vs 5.5%; 0.75-1.22), and major gastrointestinal bleeding (1.3% vs 1.5%; 0.57-1.47) between patients receiving cilostazol and those receiving clopidogrel. In subgroup analysis, cilostazol was associated with a lower incidence of recurrent ischemic stroke compared to clopidogrel in hypertensive patients (2.5% vs 3.9%; interaction P = 0.041). This real-world study suggests that cilostazol is effective and safe for noncardioembolic ischemic stroke and may be associated with better effectiveness in hypertensive patients compared to clopidogrel.

Early versus Later Anticoagulation for Stroke with Atrial Fibrillation

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

Outcomes of patients with atrial fibrillation and ischemic stroke while on oral anticoagulation.

The prognosis of patients with atrial fibrillation (AF) and ischemic stroke while taking oral anticoagulation is poorly understood. This study aimed to characterize the outcomes of patients following a stroke event while on oral anticoagulation. Individual participant data from five pivotal randomized trials of antithrombotic therapy in AF were used to assess the outcomes of patients with a post-randomization ischemic stroke while on study medication (warfarin, standard-, or lower-dose direct oral anticoagulant regimen) during trial follow-up. The primary outcome was recurrent ischemic stroke after the first post-randomization ischemic stroke. The primary analysis included 1163 patients with a first post-randomization ischemic stroke while on study medication (median age 73 years, 39.3% female, 35.4% history of stroke before trial enrollment). During a median continued follow-up of 337 days, 74 patients had a recurrent ischemic stroke [cumulative incidence at 1 year: 7.0%, 95% confidence interval (CI) 5.2%-8.7%]. The cumulative incidence of mortality at 3 months after stroke was 12.4% (95% CI 10.5%-14.4%). Consistent results for the incidence of recurrent ischemic stroke at 1 year were obtained in an analysis accounting for the competing risk of death (6.2%, 95% CI 4.8%-7.9%) and in a landmark analysis excluding the first 2 weeks after the index stroke and only including patients without permanent study drug discontinuation since then (6.8%, 95% CI 4.6%-8.9%). Patients with AF and ischemic stroke while on oral anticoagulation are at increased risk of recurrent ischemic stroke and death. These patients currently have an unmet medical need.

The Contribution of Inflammation to Stroke Recurrence Attenuates at Low LDL-C Levels.

Residual inflammation risk refers to inflammation that still increases the risk of cardiovascular disease after the level of low-density lipoprotein cholesterol (LDL-C) reached the target (＜70 mg/dL). However, whether inflammation is still an important issue even if very low LDL-C levels have been achieved remains unclear. This study aimed to investigate the contribution of inflammation to stroke recurrence on different LDL-C levels following ischemic stroke (IS) or transient ischemic attack (TIA). A total of 10499 IS/TIA patients whose LDL-C and high-sensitivity C-reactive protein (hsCRP) were measured were selected from the Third China National Stroke Registry. The cutoff values were set to 25, 35, 45, 55, 70, and 100 mg/dL for LDL-C, whereas the threshold values of hsCRP and interleukin-6 (IL-6) were 2 mg/L and 1.65 ng/L, respectively. Based on each group of LDL-C, Cox regressions were conducted to investigate the associations between inflammation and recurrent stroke within 1 year. The associations between baseline hsCRP levels and stroke recurrence were non-significant in groups with LDL-C ＜55 mg/dL (P＞0.05). After stratification by baseline LDL-C of 55 mg/dL, hsCRP ≥ 2 mg/L (10.9% versus 7.5%, P＜0.0001) and IL-6 ≥ 1.65 ng/L (9.8% versus 7.4%, P=0.0002) were found to be related to a high incidence of recurrent IS among patients with LDL-C ≥ 55 mg/dL; however, no associations were observed among patients with LDL-C ＜55 mg/dL. Compared with low inflammation (both hsCRP ＜2 mg/L and IL-6 ＜1.65 ng/L), high inflammation (both hsCRP ≥ 2 mg/L and IL-6 ≥ 1.65 ng/L) was significantly associated with stroke recurrence when LDL-C ≥ 55 mg/dL (adjusted HR 1.38, 95% CI 1.10-1.74), whereas this association was not observed when LDL-C ＜55 mg/dL (adjusted HR, 0.72; 95% CI, 0.41-1.25). For IS/TIA patients, the contribution of inflammation to stroke recurrence seems to be attenuated at a low level of LDL-C.

Covert Brain Infarction as a Risk Factor for Stroke Recurrence in Patients With Atrial Fibrillation.

We aimed to evaluate covert brain infarction (CBI), frequently encountered during the diagnostic work-up of acute ischemic stroke, as a risk factor for stroke recurrence in patients with atrial fibrillation (AF). For this prospective cohort study, from patients with acute ischemic stroke hospitalized at 14 centers between 2017 and 2019, we enrolled AF patients without history of stroke or transient ischemic attack and divided them into the CBI (+) and CBI (-) groups. The 2 groups were compared regarding the 1-year cumulative incidence of recurrent ischemic stroke and all-cause mortality using the Fine and Gray subdistribution hazard model with nonstroke death as a competing risk and the Cox frailty model, respectively. Each CBI lesion was also categorized into either embolic-appearing (EA) or non-EA pattern CBI. Adjusted hazard ratios and 95% CIs of any CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were estimated. Among 1383 first-ever stroke patients with AF, 578 patients (41.8%) had CBI. Of these 578 with CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were 61.8% (n=357), 21.8% (n=126), and 16.4% (n=95), respectively. The estimated 1-year cumulative incidence of recurrent ischemic stroke was 5.2% and 1.9% in the CBI (+) and CBI (-) groups, respectively (P=0.001 by Gray test). CBI increased the risk of recurrent ischemic stroke (adjusted hazard ratio [95% CI], 2.91 [1.44-5.88]) but did not the risk of all-cause mortality (1.32 [0.97-1.80]). The EA pattern CBI only and both CBIs elevated the risk of recurrent ischemic stroke (2.76 [1.32-5.77] and 5.39 [2.25-12.91], respectively), while the non-EA pattern only did not (1.44 [0.40-5.16]). Our study suggests that AF patients with CBI might have increased risk of recurrent stroke. CBI could be considered when estimating the stroke risk in patients with AF.

Actovegin in the management of patients after ischemic stroke: A systematic review.

BackgroundActovegin is a hemodialysate of calf’s blood and has been used for several decades in the countries of Central Asia, East Asia, Russia and some European countries. It has been used to treat patients with various neurological conditions, vascular disorders, and ischemic stroke.ObjectivesTo perform a systematic review to evaluate the effect of Actovegin in patients who have suffered an ischemic stroke.MethodsA search of MEDLINE, PubMed, Cochrane and Embase was carried out from inception to October 10, 2021 for clinical trials and observational studies with a control group, published in English or Russian.ResultsOf 220 identified unique records, 84 full-text articles were screened, and 5 studies were selected that met the inclusion criteria. This included 4 observational studies with control groups and one randomized, placebo-controlled clinical trial. These studies enrolled a total of 3879 patients of which 720 patients received Actovegin administered intravenously and/or orally for a duration ranging from 10 to 180 days. Because of study heterogeneity, meta-analysis was not performed. No consistent evidence on improved survival, quality of life, neurologic symptoms, activities of daily living or disability was identified. One study showed statistically significant improvements in the Alzheimer’s Disease Assessment Scale, cognitive subscale, extended version (ADAS-cog+) for Actovegin compared with placebo at 6 months but the clinical relevance of this change is uncertain. One study reported a higher incidence of recurrent ischemic stroke, transient ischemic attack or intracerebral hemorrhage in patients taking Actovegin compared to placebo.ConclusionsThe benefits of Actovegin are uncertain and that there is potential risk of harm in patients with stroke. More evidence is needed from rigorously designed clinical trials to justify the role of Actovegin in patients with ischemic stroke.

Timing of Direct Oral Anticoagulants for Hemorrhagic Transformation After Endovascular Treatment in Acute Ischemic Stroke

ObjectivesThe purpose of this study is to investigate the relationship between the timing of starting direct oral anticoagulants (DOACs) and subsequent clinical outcomes in patients with hemorrhagic transformation (HT) after endovascular treatment (EVT). Materials and methodsThe subjects were patients with acute cardioembolic stroke who underwent EVT and received DOACs in our department from February 2017 to August 2021. Based on CT at 24 h after EVT, the patients were classified using European Collaborative Acute Stroke Study criteria into three groups: no HT, hemorrhagic infarction (HI), and parenchymal hematoma (PH). Outcomes were assessed for incidence of recurrent ischemic stroke (RIS), new intracranial hemorrhage (ICH), and worsened HT associated with DOACs. ResultsOf 111 patients, 29 (26.1%) had HT, including 16 (14.4%) with HI and 13 (11.7%) with PH. The start of DOACs was significantly delayed in the PH group (no HT: 1.0 (1.0–3.0) days vs. HI: 3.0 (2.0–5.0) days vs. PH: 7.0 (7.0–10.0) days, P < 0.01). The incidence of RIS did not differ significantly among the three groups, but tended to be higher in the PH group (no HT: 3.7% vs. HI: 6.3% vs. PH: 15.4%, p = 0.12). There were no cases of new symptomatic ICH. New asymptomatic ICH occurred in 2 cases in the no HT group. Worsened HT after initiation of DOACs did not occur in the HI or PH group. ConclusionsThe timing of starting DOACs in patients with HT after EVT may be divided by subtypes of HI and PH. In patients with HI, early initiation of DOACs can prevent RIS and is unlikely to cause new ICH or worsened HI. In PH, initiation of DOACs within 14 days appears to be safe and does not exacerbate PH. The later the start of DOACs, the higher the frequency of RIS, so early initiation of DOACs is desirable.

Abstract WP184: The Risk Of Stroke Recurrence According To Neuroimaging Parameters In Patients With Acute Ischemic Stroke And Atrial Fibrillation

Purpose: The usefulness of the existing risk stratification tools for atrial fibrillation (AF) is limited in predicting stroke recurrence in patients with acute ischemic stroke (AIS). Neuroimaging parameters obtained from diagnostic work-up of AIS could offer more elaborate prediction. Methods: A multicenter prospective cohort of AIS patients with AF recruited from 14 university hospitals or regional stroke centers were followed up for recurrent ischemic stroke (RIS) and a composite of all stroke and TIA. Neuroimaging features were derived from acute and chronic infarction patterns, and SVD markers such as lacunes, CMBs, and WMH. Cumulative incidences according to each neuroimaging parameter were estimated and compared using the Kaplan-Meier method with log-rank test and multivariable cause-specific hazard models with death as a competing risk. Results: A total of 2,270 patients were followed up for 431 days (IQR, 365-735), during which 111 RISs and 130 composite outcomes occurred. In unadjusted analysis, lesion multiplicity among acute infarction patterns, the presence of chronic non-lacunar infarction, and the presence of lacunes among SVD markers increased the risk of RIS significantly (Table). Other neuroimaging features such as territory multiplicity and location, confluency, topography, and size of acute lesions, lesion multiplicity, territory multiplicity, confluency, topography, and size of chronic infarction, number of lacunes, presence of CMBs, and WMH did not affect the incidence of RIS. The adjusted hazard ratios of lesion multiplicity of acute infarction, chronic infarction and lacunes were 1.45 (95% CI, 0.99-2.11), 1.57 (1.06-2.34) and 1.97 (1.30-2.98) for RIS, respectively. Similar findings were obtained for the composite outcome. Conclusions: Several neuroimaging markers were associated with recurrent ischemic stroke in AIS with AF. This could pave the way to a new stratification scheme for AF including neuroimaging parameters.

The Role of Lipid-Lowering Treatment in the Secondary Prevention of Ischemic Stroke.

Dyslipidemia is a major modifiable risk factor for ischemic stroke. Treatment with statins reduces the incidence of recurrent ischemic stroke and also reduces coronary events in patients with a history of ischemic stroke. Therefore, statins represent an important component of secondary prevention of ischemic stroke. In patients who do not achieve low-density lipoprotein cholesterol (LDL-C) targets despite treatment with the maximal tolerated dose of a potent statin, ezetimibe should be added to their lipid-lowering treatment and also appears to reduce the risk of cardiovascular events. Selected patients who do not achieve LDL-C targets despite statin/ezetimibe combination are candidates for receiving proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Finally, it appears that adding icosapent ethyl might also reduce cardiovascular morbidity in patients who have achieved LDL-C targets but have persistently elevated triglyceride levels.

Fate of Patients with Chronic Cerebrovascular Steno-occlusive Disease According to Change of Cerebral Perfusion, Cerebrovascular Reserved, and Incidence of Recurrent Ischemic Stroke.

Objective:The objective is to demonstrate change of cerebral perfusion and cerebrovascular reserve (CVR) in treating patients with cerebrovascular steno-occlusive disease stratified by change of cerebral perfusion and CVR.Methods:Retrospective review patients with radiographic proven major cerebrovascular steno-occlusive disease whom underwent cerebral perfusion imaging with vasoactive stimuli stress test in Siriraj Hospital and Bangkok General Hospital during 2010–2018. Medical records were also reviewed. Radiographic findings, cerebral perfusion parameters and signal change during the stress test were reviewed and used to categorize into three groups.Results:There were 40 patients sent to radiology department for the evaluation of CVR. One patient had airway problem during the procedure and was excluded. Remaining 39 patients were included in this study (32 males and 7 females, mean age of 54.55 years). In 42 sites involved, 28 (66%) were internal carotid artery, 14 (33%) were middle cerebral arteries. Laterality is left side in 20 cases, right side in 14 cases, and bilateral in 5 cases. Poor CVR response (increased cerebral blood flow <10%) was found in 9 patients (2 severe stenoses and 7 total occlusions). The mean follow-up time was 28.9 months. Eight cases (20.5%) underwent surgical treatment; surgical bypasses and endovascular interventions. Only one patient had subsequential ischemic symptom at immediate postoperative vascular bypass surgery. The remaining patients had no report of progressive or recurrent neurological deficit symptom.Conclusion:Poor CVR response is more often found in higher degree of steno-occlusion. Even inconclusive predicting incidence of recurrent ischemic stroke, CVR that reflects the capacity of neuro-autoregulation.

Atrial Fibrillation-Associated Ischemic Stroke Patients With Prior Anticoagulation Have Higher Risk for Recurrent Stroke.

Background and Purpose- Ischemic stroke associated with nonvalvular atrial fibrillation (NVAF) despite prior anticoagulation may indicate underlying problems that nullify the stroke-preventing effects of oral anticoagulants. We aimed to evaluate the risk for recurrent stroke in patients with NVAF with prior anticoagulation, compared with that in patients without prior anticoagulation. Methods- This study comprised pooled individual patient data on NVAF-associated acute ischemic stroke or transient ischemic attack from 2011 to 2014 arising from the Clinical Research Collaboration for Stroke in Korea (15 South Korean stroke centers) and the Stroke Acute Management With Urgent Risk-Factor Assessment and Improvement-NVAF registry (18 Japanese stroke centers). Data on 4841 eligible patients from the Clinical Research Collaboration for Stroke in Korea registry were pooled with data on all patients (n=1192) in the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-NVAF registry. The primary outcome was recurrent ischemic stroke. The secondary outcomes were hemorrhagic stroke and all-cause death. Outcome events were captured up to 1 year after the index event. Results- Among the 6033 patients in the full cohort, 5645 patients were analyzed, of whom 1129 patients (20.0%) had received prior anticoagulation. Median age was 75 years (interquartile range, 69-81 years), and 2649 patients (46.9%) were women. Follow-up data of 4617 patient-years (median follow-up 365 days, interquartile range 335-365 days) were available. The cumulative incidence of recurrent ischemic stroke in patients with prior anticoagulation was 5.3% (60/1129), compared with the 2.9% (130/4516) incidence in patients without prior anticoagulation. The risk for recurrent ischemic stroke was higher in patients with prior anticoagulation than in those without (multivariable Cox shared-frailty model, hazard ratio 1.50 [95% CI, 1.02-2.21]). No significant differences in the risks for hemorrhagic stroke and mortality were seen between the 2 groups. Conclusions- The risk for recurrent ischemic stroke may be higher in NVAF-associated stroke patients with prior anticoagulation than in those without prior anticoagulation. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01581502.

Recurrent ischemic stroke: Incidence, predictors, and impact on mortality.

Background and purposeRecurrent ischemic stroke (IS) or TIA is frequent with a considerable variation in incidence and mortality across populations. Current data on stroke recurrence and mortality are useful to examine trends, risk factors, and treatment effects. In this study, we calculated the incidence of recurrent IS or TIA in a hospital‐based stroke population in Western Norway, investigated recurrence factors, and estimated the effect of recurrence on all‐cause mortality.MethodsThis prospective cohort study registered recurrence and mortality among 1872 IS and TIA survivors admitted to the stroke unit at Haukeland University Hospital between July 2007 and December 2013. Recurrence and death until September 1, 2016, were identified by medical chart review. Cumulative incidences of recurrence were estimated with a competing risks Cox model. Multivariate Cox models were used to examine recurrence factors and mortality.ResultsDuring follow‐up, 220 patients had 277 recurrent IS or TIAs. The cumulative recurrence rate was 5.4% at 1 year, 11.3% at 5 years, and 14.2% at the end of follow‐up. Hypertension (HR = 1.65, 95% CI 1.21‐2.25), prior symptomatic stroke (HR = 1.63, 95% CI 1.18‐2.24), chronic infarcts on MRI (HR = 1.48, 95% CI 1.10‐1.99), and age (HR 1.02/year, 95% CI 1.00‐1.03) were independently associated with recurrence. A total of 668 (35.7%) patients died during follow‐up. Recurrence significantly increased the all‐cause mortality (HR = 2.55, 95% CI 2.04‐3.18).ConclusionsThe risk of recurrent IS stroke or TIA was modest in our population and was associated with previously established risk factors. Recurrence more than doubled the all‐cause mortality.

Preadmission use of glucocorticoids and risk of cardiovascular events in patients with ischemic stroke

Essentials The risk of thrombosis among ischemic stroke patients using glucocorticoids is unknown. We examined the risk of thrombosis in 98 487 ischemic stroke patients, by glucocorticoid use. Myocardial infarction and venous thromboembolism risk was increased in glucocorticoid users. Hemorrhagic stroke risk was lower and recurrent ischemic stroke the same in glucocorticoid users. SUMMARY: Background Glucocorticoid users have a high mortality rate following stroke, but the underlying clinical pathways are poorly understood. Objectives To examine the risk of cardiovascular events among ischemic stroke patients using glucocorticoids. Methods We conducted a nationwide population-based cohort study by using medical registries in Denmark. We identified all patients hospitalized with a first-time ischemic stroke (2004-2013). We categorized glucocorticoid use into current use (last prescription redemption ≤ 90 days before admission), former use, and non-use. With non-users as reference, we studied the risks of recurrent ischemic stroke, hemorrhagic stroke, myocardial infarction and venous thromboembolism associated with glucocorticoid use. Comorbidity and comedication-adjusted 1-year hazard ratios (aHRs) with 95% confidence intervals (CIs) were computed on the basis of Cox regression analysis. Results We identified 98 487 patients with a first-time (index) ischemic stroke. After the index stroke, the 1-year cumulative incidence of recurrent ischemic stroke was 16.4% among current glucocorticoid users, whereas risks were lower for hemorrhagic stroke (0.46%), myocardial infarction (1.35%), and venous thromboembolism (0.98%). Among current glucocorticoid users, aHRs were increased for myocardial infarction (1.32, 95% CI 0.98-1.76) and venous thromboembolism (1.39, 95% CI 0.99-1.94), whereas the risk of hemorrhagic stroke was reduced (aHR 0.60, 95% CI 0.38-0.93). There was no association with recurrent ischemic stroke (aHR 1.01, 95% CI 0.94-1.09). Conclusions During the first year after ischemic stroke, current glucocorticoid use was associated with moderately increased risks of myocardial infarction and venous thromboembolism, and a lower risk of hemorrhagic stroke, whereas the risk of recurrent ischemic stroke was not affected.

Comparison of the flexible parametric survival model and Cox model in estimating Markov transition probabilities using real-world data.

Background and objectiveMarkov micro-simulation models are being increasingly used in health economic evaluations. An important feature of the Markov micro-simulation model is its ability to consider transition probabilities of heterogeneous subgroups with different risk profiles. A survival analysis is generally performed to accurately estimate the transition probabilities associated with the risk profiles. This study aimed to apply a flexible parametric survival model (FPSM) to estimate individual transition probabilities.Materials and methodsThe data were obtained from a cohort study investigating ischemic stroke outcomes in Western China. In total, 585 subjects were included in the analysis. To explore the goodness of fit of the FPSM, we compared the estimated hazard ratios and baseline cumulative hazards, both of which are necessary to the calculate individual transition probabilities, and the Markov micro-simulation models constructed using the FPSM and Cox model to determine the validity of the two Markov micro-simulation models and cost-effectiveness results.ResultsThe flexible parametric proportional hazards model produced hazard ratio and baseline cumulative hazard estimates that were similar to those obtained using the Cox proportional hazards model. The simulated cumulative incidence of recurrent ischemic stroke and 5-years cost-effectiveness of Incremental cost-effectiveness Ratios (ICERs) were also similar using the two approaches. A discrepancy in the results was evident between the 5-years cost-effectiveness and the 10-years cost-effectiveness of ICERs, which were approximately 0.9 million (China Yuan) and 0.5 million (China Yuan), respectively.ConclusionsThe flexible parametric survival model represents a good approach for estimating individual transition probabilities for a Markov micro-simulation model.

Risk of Recurrent Ischemic Stroke with Unintended Low-Dose Oral Anticoagulant Therapy and Optimal Timing of Review

Direct oral anticoagulant (DOAC) dose is adjusted according to manufacturer's recommendations when introduced. However, subsequent changes from appropriate DOAC doses to "unintended" inappropriate low-dose DOAC (ILD) due to increased body weight (BW) or decreased serum creatinine concentration might be overlooked. We investigated outcomes in patients receiving appropriate DOAC, "intended" ILD, or unintended ILD, to determine the optimal review time for DOAC doses and associated factors. This single-center, retrospective cohort study included inpatients receiving apixaban for stroke prevention between August 2015 and July 2017. Primary outcome was whether starting DOAC dose was selected according to manufacturer's recommendations and whether that dose remained appropriate thereafter. Secondary outcome was the incidence of recurrent ischemic stroke and intracranial bleeding during therapy. Average rates of change in BW, creatinine, and creatinine clearance (CrCl) were evaluated after hospitalization every 10 ± 3 days. During the study period, 120 patients received apixaban; 112 (93.3%) commenced appropriate DOAC doses, and 8 (6.7%) commenced intended ILD doses. Of the 112 patients on appropriate DOAC doses, 7 (6.3%) changed to unintended ILD doses because of increased BW (n = 4) or decreased creatinine (n = 3). The rate of recurrent ischemic stroke differed significantly between the appropriate DOAC dose and the intended or unintended ILD dose group (1.9% [2 of 105] versus 20.0% [3 of 15], P = .014). BW and renal function had stabilized after 20 ± 3 days posthospitalization. Receiving ILD doses, especially unintended, might be a risk factor for recurrent ischemic stroke and DOAC dose should be reviewed around 20 ± 3 days posthospitalization.

Research progress on risk factors for recurrent ischemic stroke

Ischemic stroke has a high disability rate, mortality and recurrence rate. The term of recurrent ischemic stroke is patient's conditions occur again after improvement or recovery of ischemic stroke. The disability rate and mortality of recurrent ischemic stroke will be significantly higher than those after the first onset. In this paper, the related risk factors for recurrent ischemic stroke were reviewed to provide the basis of secondary prevention for ischemic stroke, and to reduce the incidence of recurrent ischemic stroke. DOI: 10.3969/j.issn.1672-6731.2017.10.011