Noncardioembolic Ischemic Stroke Research Articles

Assessment of of twenty-five variants of polymorphic genes for lipid and carbohydrate metabolism, vascular inflammation and the neurotransmitter system in the first non-cardioembolic ischemic stroke

Abstract The study of the relationship between various of gene polymorphism: APOA-V (rs34282181), APOA-V (rs619054), APOC-IV (rs1132899), LPL (rs199675233), LP(a) (rs41267817), APOB (rs1042031), APOB (rs676210), APOC-IV (rs1132899), APOH (rs4581), ANGPT4 (rs1044250), APOE (rs5174), APOE (rs 7412), APOE (rs 429358), APOD (rs7659), ADIPOQ (rs17366743), ADIPOQ (rs185847354), ADIROR (rs12342), TNFα (rs1800620), VEGFA (rs 62401172), IL6 (rs56383910), IL8 (rs1803205), MTHFR (rs1801131), MTHFR (rs1801133), GRM 1 (rs1047005), GRM 3 (rs2228595), BDNF (rs6265) and the development of the first non-cardioembolic ischemic stroke Material and methods The alleles frequencies and genotypes assessed for 25 mono-nucleotide polymorphic gene variants in 206 patients, who had first non-cardioembolic ischemic stroke, and 206 persons with no stroke, comparable with age, gender, place of living and ethnicity. Genotyping of polymorphisms was done with the prepared TaqMan probes. Genotyping of single nucleotide polymorphisms of genes: APOA-V (rs34282181), APOA-V (rs619054), APOC-IV (rs1132899), LPL (rs199675233), LP(a) (rs41267817), APOB (rs1042031), APOB (rs676210), APOC-IV (rs1132899), APOH (rs4581), ANGPT4 (rs1044250), APOE (rs5174), APOE (rs 7412), APOE (rs 429358), APOD (rs7659), ADIPOQ (rs17366743), ADIPOQ (rs185847354), ADIROR (rs12342), TNFα (rs1800620), VEGFA (rs 62401172), IL6 (rs56383910), IL8 (rs1803205), MTHFR (rs1801131), MTHFR (rs1801133), GRM 1 (rs1047005), GRM 3 (rs2228595), BDNF (rs6265) using ready-made TaqMan probes was carried out. Results For polymorphisms ApoD (rs7659), ApoA5 (rs619054), ApoB (rs676210), IL8 (rs1803205) there was significant difference between groups in the variety of minor alleles and genotypes. Conclusions There is significant relation of mononucleotide polymorhpisms of the genes APOD (rs7659), ApoA5 (rs619054), ApoB (rs676210), IL8 (rs1803205) with the development of the first non-cardioembolic ischemic stroke In the studied groups. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Moscow Center for Neurorehabilitation

Disease Burden Following Non-Cardioembolic Minor Ischemic Stroke or High-Risk TIA: A GWTG-Stroke Study

BackgroundLimited real-world data are available on outcomes following non-cardioembolic minor ischemic stroke (IS) or high-risk transient ischemic attack (TIA), particularly in the United States (US). We examined outcomes and Medicare payments following any severity IS or TIA as well as the subgroup with minor IS or high-risk TIA. MethodsMedicare beneficiaries >65 years were identified using US nationwide Get with the Guidelines (GWTG)-Stroke Registry linked to Medicare claims data. The cohort consisted of patients enrolled in Medicare fee-for-service plan, hospitalized with non-cardioembolic IS or TIA between 2011 and 2014, segmenting a subgroup with minor IS (National Institute of Health Stroke Scale [NIHSS] ≤5) or high-risk TIA (ABCD2-score ≥6) compatible with the THALES clinical trial population. Outcomes included functional status at discharge, clinical outcomes (all-cause mortality, ischemic stroke, and hemorrhagic stroke, individually and as a composite), hospitalizations, and population average inpatient Medicare payments following non-cardioembolic IS or TIA. ResultsThe THALES-compatible cohort included 62,518 patients from 1471 hospitals. At discharge, 37.0% were unable to ambulate without assistance, and 96.2% were prescribed antiplatelet therapy. Cumulative incidences at 30 days, 90 days, and 1 year for the composite outcome were 3.7%, 7.6%, and 17.2% and 2.4%, 4.0%, and 7.3% for subsequent stroke. The mean Medicare payment for the index hospitalization was $7951. The cumulative all-cause inpatient Medicare spending per patient (with or without any subsequent admission) at 30 days and 1 year from discharge was $1451 and $8105, respectively. ConclusionsThe burden of illness for minor IS/high-risk TIA patients indicates an important unmet need. Improved therapeutic options may offer a significant impact on both patient outcomes and Medicare spending.

Remote platelet function testing using P-selectin expression in patients with recent cerebral ischaemia on clopidogrel

BackgroundAntiplatelet agents reduce recurrence after cerebral ischaemia but are not effective in all patients, in part because of treatment resistance. The primary aim was to assess the proportion of patients...

Colchicine in Patients With Acute Coronary Syndrome: The Australian COPS Randomized Clinical Trial.

Inflammation plays a crucial role in clinical manifestations and complications of acute coronary syndromes (ACS). Colchicine, a commonly used treatment for gout, has recently emerged as a novel therapeutic option in cardiovascular medicine owing to its anti-inflammatory properties. We sought to determine the potential usefulness of colchicine treatment in patients with ACS. This was a multicenter, randomized, double-blind, placebo-controlled trial involving 17 hospitals in Australia that provide acute cardiac care service. Eligible participants were adults (18-85 years) who presented with ACS and had evidence of coronary artery disease on coronary angiography managed with either percutaneous coronary intervention or medical therapy. Patients were assigned to receive either colchicine (0.5 mg twice daily for the first month, then 0.5 mg daily for 11 months) or placebo, in addition to standard secondary prevention pharmacotherapy, and were followed up for a minimum of 12 months. The primary outcome was a composite of all-cause mortality, ACS, ischemia-driven (unplanned) urgent revascularization, and noncardioembolic ischemic stroke in a time to event analysis. A total of 795 patients were recruited between December 2015 and September 2018 (mean age, 59.8±10.3 years; 21% female), with 396 assigned to the colchicine group and 399 to the placebo group. Over the 12-month follow-up, there were 24 events in the colchicine group compared with 38 events in the placebo group (P=0.09, log-rank). There was a higher rate of total death (8 versus 1; P=0.017, log-rank) and, in particular, noncardiovascular death in the colchicine group (5 versus 0; P=0.024, log-rank). The rates of reported adverse effects were not different (colchicine 23.0% versus placebo 24.3%), and they were predominantly gastrointestinal symptoms (colchicine, 23.0% versus placebo, 20.8%). The addition of colchicine to standard medical therapy did not significantly affect cardiovascular outcomes at 12 months in patients with ACS and was associated with a higher rate of mortality. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12615000861550.

RETRACTED ARTICLE: Dual versus mono antiplatelet therapy for acute non- cardio embolic ischemic stroke or transient ischemic attack, an efficacy and safety analysis - updated meta-analysis

BackgroundNew evidence on the efficacy and safety of dual antiplatelet therapy for secondary stroke prevention have been realized in the recent years. An updated meta analysis was done to determine the effect of the various dual antiplatelets vs aspirin alone on recurrence rate of ischemic stroke, cardiovascular morbidity and mortality, and its safety profile as reported through major bleeding.MethodsPubMed, Cochrane and Science Direct data bases were utilized, RCTs evaluating dual antiplatelet vs mono antiplatelet therapy for acute ischemic stroke or transient ischemic attack within < 72 h from ictus were searched up to July 2019. Risk ratio at 95% confidence intervals were calculated to evaluate stroke recurrence, cardiac events and mortality, and major bleeding.ResultsSixteen randomized controlled trials with a population of 28, 032 patients were pooled into a meta-analysis. Dual antiplatelet therapy was significantly superior over mono antiplatelet therapy in the reduction of stroke (RR 0.75, 95% CI:0.68–0.83, p value< 0.00001) and composite events namely cardiovascular morbidity and mortality (0.73 95% CI: 0.65–0.82, p value < 0.00001), while bleeding events were noted to be not significant (1.22 95% CI: 0.87–1.70, p value = 0.25).ConclusionIn acute non-cardioembolic ischemic strokes or those who have suffered a transient ischemic attack, dual antiplatelet therapy was associated with efficacy in stroke recurrence and composite cardiac events, with a non-significant risk of major bleeding.

Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA

BackgroundTrials have evaluated the use of clopidogrel and aspirin to prevent stroke after an ischemic stroke or transient ischemic attack (TIA). In a previous trial, ticagrelor was not better than aspirin in preventing vascular events or death after stroke or TIA. The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied.MethodsWe conducted a randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less (range, 0 to 42, with higher scores indicating more severe stroke), or TIA and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding.ResultsA total of 11,016 patients underwent randomization (5523 in the ticagrelor–aspirin group and 5493 in the aspirin group). A primary-outcome event occurred in 303 patients (5.5%) in the ticagrelor–aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P=0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor–aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P=0.004). The incidence of disability did not differ significantly between the two groups. Severe bleeding occurred in 28 patients (0.5%) in the ticagrelor–aspirin group and in 7 patients (0.1%) in the aspirin group (P=0.001).ConclusionsAmong patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor–aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor. (Funded by AstraZeneca; THALES ClinicalTrial.gov number, NCT03354429.)

Impact of Sleep-Disordered Breathing on Functional Outcomes in Ischemic Stroke: A Cardiopulmonary Coupling Analysis.

Cardiopulmonary coupling (CPC) analysis is an easily assessable method to evaluate sleep-disordered breathing (SDB); however, its prognostic impact in patients with acute ischemic stroke needs to be investigated. We performed a CPC analysis using Holter monitoring at the early stage of noncardioembolic ischemic stroke to investigate the prognostic effect of SDB on functional impairment at the 3-month follow-up. A total 615 patients with acute noncardioembolic ischemic stroke who underwent Holter monitoring within 30 days of stroke onset were enrolled from a multicenter, prospective, all-comer cohort. CPC analysis was conducted, and SDB was defined by the presence of narrow-band coupling during sleep time. We investigated the association between SDB and functional impairment at 3 months as measured by the modified Rankin Scale. Narrow-band coupling was present in 191 (31.1%) of 615 patients (mean age 64.5±12.6 years). The narrow-band group showed a significantly higher rate of severe functional impairment (modified Rankin Scale score >2; 45.5% versus 12.9%, P<0.001) and persistent disability (Δmodified Rankin Scale score ≤0; 53.9% versus 39.8%, P<0.001) at the 3-month follow-up. In multivariate analysis, narrow-band coupling was an independent predictor of higher risk of severe and persistent functional impairment at 3 months (odds ratio, 3.98 [95% CI, 2.34-6.78]; P<0.001; and odds ratio, 1.81 [95% CI, 1.23-2.66]; P<0.001, respectively). The results remained consistent after propensity-score matched analysis with 157 patient pairs (C-statistic=0.770). SDB assessed by CPC analysis at the early stage of ischemic stroke could predict severe and prolonged functional impairment at 3 months. CPC analysis using Holter monitoring can help predicting functional impairment in acute ischemic stroke.

Safety and Efficacy of Prasugrel in Elderly/Low Body Weight Japanese Patients with Ischemic Stroke: Randomized PRASTRO-II

Introduction: The safety of prasugrel in elderly and/or low body weight Japanese patients with ischemic stroke who have a relatively high bleeding risk with antiplatelet therapy remains unknown. Objective: We aimed to investigate the safety and efficacy of long-term prasugrel monotherapy for stroke prevention compared with clopidogrel in elderly and/or low body weight Japanese patients with non-cardioembolic ischemic stroke. Methods: In this randomized, double-blind, comparative, phase III study, elderly (age ≥75 years) and/or low body weight (≤50 kg) Japanese patients with a previous history of non-cardioembolic ischemic stroke were assigned to a prasugrel 3.75 mg (PRA3.75) group, a prasugrel 2.5 mg (PRA2.5) group, or a clopidogrel 50 mg (CLO50) group and followed up for 48 weeks. The primary safety endpoint was the combined incidence of primary safety events, defined as life-threatening, major, and other clinically relevant bleeding. The efficacy endpoint was a composite of ischemic stroke, myocardial infarction, and death from other vascular causes. Results: A total of 654 patients (age 76.4 ± 7.3 years, body weight 55.6 ± 9.3 kg, women 43.9%) from 74 medical institutions within Japan were enrolled. The combined incidence (95% CI) of primary safety events was 4.2% (1.9–7.8%), 1.9% (0.5–4.7%), and 3.6% (1.6–6.9%) in the PRA3.75 group (n = 216), PRA2.5 group (n = 215), and CLO50 group (n = 223), respectively (hazard ratios [HR] PRA3.75/CLO50, 1.13 [0.44–2.93]; PRA2.5/CLO50, 0.51 [0.15–1.69]). The incidences of bleeding leading to treatment discontinuation (95% CI) were 2.3% (0.8–5.3%), 0.9% (0.1–3.3%), and 2.2% (0.7–5.2%) in the PRA3.75, PRA2.5, and CLO50 groups, respectively (HRs PRA3.75/CLO50, 1.01 [0.29–3.48]; PRA2.5/CLO50, 0.41 [0.08–2.12]). There was no significant difference in all bleeding events between groups. The incidence of ischemic stroke, myocardial infarction, and death from other vascular causes was lower, but not significantly so, in patients treated with prasugrel than in patients treated with clopidogrel: PRA3.75, 0.0% (0/216); PRA2.5, 3.3% (7/215); and CLO50, 3.6% (8/223; HRs PRA3.75/CLO50, 0.00 [0.00–0.00]; PRA2.5/CLO50, 0.90 [0.32–2.47]). Conclusions: Elderly and/or low body weight ­Japanese patients with previous non-cardioembolic ischemic stroke who received PRA3.75 showed similar results in terms of primary safety endpoint, and a numerically lower incidence of ischemic stroke, myocardial infarction, and death from other vascular causes, compared with those who received CLO50.

Early increment of soluble triggering receptor expressed on myeloid cells 2 in plasma might be a predictor of poor outcome after ischemic stroke

Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is derived from cleavage of TREM2, which is expressed on the cell surface of microlgia and other tissue-specific macrophages. In the present study, the changes in the sTREM2 levels after ischemic stroke (IS) and their association with clinical outcomes were evaluated. A total of 43 patients diagnosed with non-cardioembolic IS between June 2011 and May 2014 were consecutively included in this study. Patients treated with intravenous thrombolysis or intra-arterial thrombectomy were excluded. Plasma samples were collected three times (days 1, 7, and 90) after ictus. The sTREM2 level was measured in the samples using the highly sensitive solid-phase proximity ligation assay (SP-PLA). Among the 43 subjects, higher initial NIH stroke scale (NIHSS) score (P = 0.005), early increment of sTREM2 (P < 0.001), and late decrement of sTREM2 (P = 0.002), were more common in patients with poor outcome. Based on multivariate analysis, initial NIHSS score (P = 0.015) and early increment of sTREM2 (P = 0.032) were independently associated with poor outcome. The results from the present study indicate that increment of sTREM2 level at the early phase was a predictor of poor outcome. Serial follow-up of sTREM2 may aid prognosis after stroke.

Abstract 159: Trends in Dual Antiplatelet Therapy Prescription Patterns for Secondary Prevention in Patients With Noncardioembolic Ischemic Stroke

Background: The recommendations for dual antiplatelet (DAPT aspirin + clopidogrel) for secondary stroke prevention has evolved over time. Following the publication of CHANCE trial (07/2013), the AHA/ASA updated the DAPT recommendations from Class III harm (10/2010) for patient with noncardioembolic ischemic stroke, to Class IIb benefit ≥ risk (02/2014), and Class IIa benefit &gt;&gt; risk (03/2018) for a subgroup of patients with minor stroke (NIHSS≤3). Subsequent to the last guideline update, the POINT trial (05/2018) provided further support for the effectiveness of DAPT. Methods: We evaluated antiplatelet prescription patterns of 1,024,074 noncardioembolic ischemic stroke survivors (median age 65 years and 46% women) eligible for antiplatelet therapy (no contraindications) and discharged from the Get With The Guidelines-Stroke Hospitals between Q1 2011 and Q1 2019. Results: Baseline patient characteristics were similar within the four periods: pre-CHANCE (01/2011-07/2013), pre-2014 guideline update (08/2013-02/2014), pre-POINT/2018 guideline update (03/2014-05/2018), and post-POINT (06/2018-03/2019). Use of DAPT gradually increased from 16.7% in the pre-CHANCE period, to 19.4% pre-2014 guideline update, 23.3% pre-POINT/2018 guideline update, and 29.8% post-POINT period (p&lt;0.001, Figure). Yet increase in DAPT use was observed over time for individuals with NIHSS≤3 (17.1%, 19.9%, 24.1%, and 31.4%, p&lt;0.001) and those with NIHSS&gt;3 (18.7%, 22.8%, 28.3%, and 28.3%, p&lt;0.001). Conclusions: A sustained increase in DAPT use for secondary stroke prevention was observed after publication of pivotal trials and AHA guideline updates. While recommended for minor strokes or TIA only, such increase was also observed in ischemic stroke patients with NIHSS&gt;3, where the risk-benefit ratio of DAPT remains to be established.

Abstract TP128: Determinants of Hemorrhagic Transformation After Emergent Extracranial Internal Carotid Artery Stenting for Tandem Occlusions

Background and Purpose: Extracranial internal carotid artery (ICA) lesion in the setting of tandem occlusions is a therapeutic challenge, and hemorrhagic transformation (HT) is one of the leading causes of poor clinical outcome. We aimed to determine determinants of HT for tandem occlusions undergoing emergent extracranial ICA stenting during endovascular treatment (EVT). Methods: We performed a prospective, observational cohort study of consecutive patients with non-cardioembolic ischemic stroke due to tandem occlusion who underwent EVT with extracranial ICA stent placement during the procedure from April 2013 to June 2019 in a single stroke center. We compared clinical (vascular risk factors, previous antiplatelet treatment, and IV rtPA), radiological (ASPECTS at admission and in-stent thrombosis at 24 hours) and serological (platelet count, fibrinogen, total cholesterol, HDL-cholesterol, and LDL-cholesterol) parameters according to the presence of HT in 24 hours CT-scan. Results: One-hundred and eight patients were included: 78.7% were men, mean age 68.5±14.3 years, median time from symptoms onset to treatment was 220 (150-337.5) minutes, median ASPECTS at admission was 9 (8-10). Eighty-six (79.6%) patients presented an extracranial ICA occlusion, and 22 (20.4%) a high-grade (&gt;50%) stenosis. In 88 (81.5%) patients the etiology of extracranial ICA lesion was ateroma, and in 20 (18.5%) was a dissection. Intravenous rtPA was administered in 47 (43.5%) patients. Successful recanalization (mTICI ≥2b) was achieved in 83 (76.9%) patients, and extracranial ICA recanalization in 108 (100%) patients. Type 2 diabetes (OR 1.5, 95% CI 1.1-3.5), higher fibrinogen levels (OR 4.6, 95% CI 1.6-12.9), and ASPECTS &lt;7 at admission (OR 2.1, 95% IC 1.1-5.1) were found as independent predictors of HT in multiple logistic regression analysis. Conclusions: Patients with a non-cardioembolic ischemic stroke due to tandem occlusion who present type 2 diabetes, higher fibrinogen levels, or ASPECTS &lt;7 at admission are at high risk of HT. In these particular cases, it might be useful to stent with a stent that does not need double antiplatelet treatment immediately after the procedure.

Prognostic Value of Circulating Microvesicle Subpopulations in Ischemic Stroke and TIA

Platelet microvesicles (PMV) have previously been found elevated in acute ischemic stroke (IS) and could be biomarkers for risk of recurrence. PMV surface antigens such as P-selectin and phosphatidylserine (PS) reflect platelet activation and procoagulance. Tissue factor-positive microvesicles (TF+MV) are considered procoagulant, in particular if co-expressing PS. We enumerated MV subpopulations with these surface antigens in a cohort of 211 patients with primarily non-cardioembolic IS or transient ischemic attack (TIA) and investigated their association with long-term outcome. MV concentrations were determined by flow cytometry in the acute and convalescent phase. Primary outcome was a composite of fatal and non-fatal recurrent IS or myocardial infarction. Secondary outcomes were recurrent IS and all-cause mortality. Outcome events were obtained from Swedish registers during a follow-up of 1100 patient years. Concentrations of PS-positive and PS-negative MV populations were elevated in patients compared with healthy controls in both the acute and convalescent phase. PS+TF+PMV displayed pronounced elevations, median fold change 77 in the acute phase (p < 0.0001) but were not associated with outcome, neither were PS+P-selectin+PMV. The only subpopulation positively associated with primary outcome was PS−TF+PMV, with adjusted hazard ratio of 1.86 (1.04–3.31, p = 0.036) by Cox regression. Unexpectedly, several MV subpopulations tended to be associated with reduced risk of poor long-term outcome. Our results suggest that PS+TF+PMV may be a promising marker for cerebral ischemia, and that the in vivo generation of PS−MV after IS/TIA warrants further study. Future MV studies should ideally enumerate PS+ and PS−MV subpopulations separately.

Risk Factors of Recurrent Ischemic Events after Acute Noncardiogenic Ischemic Stroke.

A considerable proportion of acute noncardiogenic ischemic stroke patients continue to experience recurrent ischemic events after standard therapy. We aimed to identify risk factors for recurrent ischemic event prediction at an early stage. 286 non-cardioembolic ischemic stroke patients with the onset of symptoms within 24 hours were enrolled. Vascular risk factors, routine laboratory data on admission, thromboelastography test seven days after clopidogrel therapy and any recurrent events within one year were assessed. Patients were divided into case group (patients with clinical adverse events, including ischemic stokes, transient ischemic attack, myocardial infarction and vascular related mortality) and control group (events-free patients). The risk of the recurrent ischemic events was determined by the receiver operating characteristic curve and multivariable logistic regression analysis. Clinical adverse events were observed in 43 patients (case group). The mean levels of Mean Platelet Volume (MPV), Platelet/Lymphocyte Ratio (PLR), Lymphocyte Count (LY) and Fibrinogen (Fib) on admission were significantly higher in the case group as compared to the control group (P<0.001). Seven days after clopidogrel therapy, the ADP-induced platelet inhibition rate (ADP%) level was lower in the case group, while the Maximum Amplitude (MA) level was higher in the case group as compared to the control group (P<0.01). The Area Under the Curve (AUC) of receiver operating characteristic(ROC) curve of LY, PLR, , Fib, MA, ADP% and MPV were 0.602, 0.614, 0.629, 0.770, 0.800 and 0.808, respectively. The logistic regression analysis showed that MPV, ADP% and MA were indeed predictive factors. MPV, ADP% and MA were risk factors of recurrent ischemic events after acute noncardiogenic ischemic stroke. Urgent assessment and individual drug therapy should be offered to these patients as soon as possible.

The role of diabetes mellitus and a gender factor in the development of a second noncardioembolic ischemic stroke

The role of diabetes mellitus and a gender factor in the development of a second noncardioembolic ischemic stroke

Construction of a predictive model for assessing the risk of noncardioembolic ischemic stroke

Construction of a predictive model for assessing the risk of noncardioembolic ischemic stroke

Therapeutic-induced hypertension in patients with noncardioembolic acute stroke.

To evaluate the safety and efficacy of induced hypertension in patients with acute ischemic stroke. In this multicenter randomized clinical trial, patients with acute noncardioembolic ischemic stroke within 24 hours of onset who were ineligible for revascularization therapy and those with progressive stroke during hospitalization were randomly assigned (1:1) to the control and intervention groups. In the intervention group, phenylephrine was administered intravenously to increase systolic blood pressure (SBP) up to 200 mm Hg. The primary efficacy endpoint was early neurologic improvement (reduction in NIH Stroke Scale [NIHSS] score of ≥2 points during the first 7 days). The secondary efficacy endpoint was a modified Rankin Scale score of 0 to 2 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage/edema, myocardial infarction, and death. In the modified intention-to-treat analyses, 76 and 77 patients were included in the intervention and control groups, respectively. After adjustment for age and initial stroke severity, induced hypertension increased the occurrence of the primary (odds ratio 2.49, 95% confidence interval [CI] 1.25-4.96, p = 0.010) and secondary (odds ratio 2.97, 95% CI 1.32-6.68, p = 0.009) efficacy endpoints. Sixty-seven (88.2%) patients of the intervention group exhibited improvements in NIHSS scores of ≥2 points during induced hypertension (mean SBP 179·7 ± 19.1 mm Hg). Safety outcomes did not significantly differ between groups. Among patients with noncardioembolic stroke who were ineligible for revascularization therapy and those with progressive stroke, phenylephrine-induced hypertension was safe and resulted in early neurologic improvement and long-term functional independence. NCT01600235. This study provides Class III evidence that for patients with acute ischemic stroke, therapeutic-induced hypertension increases the probability of early neurologic improvement.

Inter-arm Blood Pressure Difference is Associated with Recurrent Stroke in Non-cardioembolic Stroke Patients

Recurrent stroke increases mortality and aggravates the disability of stroke patients. We hypothesized that increased inter-arm systolic blood pressure difference and inter-arm diastolic blood pressure difference would be related to recurrent stroke in non-cardioembolic stroke patients. A total of 1226 consecutive non-cardioembolic first-ever ischemic stroke patients, in whom bilateral brachial blood pressures were measured by an automated ankle-brachial index measuring device, were included in our study. Recurrent stroke was defined as newly developed neurologic symptoms with relevant lesions on brain CT and/or MRI after 7 days or hospital discharge. Inter-arm systolic and diastolic blood pressure differences ≥10 mmHg were noted in 9.7% (120/1226) and 5.0% (62/1226) of patients, respectively. During a median 24 months of follow-up, 105 (8.5%) patients experienced recurrent stroke. Patients who had inter-arm systolic blood pressure difference ≥10 mmHg showed increased risk of recurrent stroke (hazard ratio:1.77, 95% confidence interval: 1.04–3.00, p = 0.033). Moreover, inter-arm diastolic blood pressure difference ≥10 mmHg was also independently associated with increased risk of recurrent stroke (hazard ratio:2.92, 95% confidence interval: 1.59–5.34, p = 0.001). In conclusion, inter-arm blood pressure difference ≥10 mmHg may be associated with increased risk recurrent stroke in non-cardioembolic stroke patients.

Cilostazol use is associated with FIM cognitive improvement during convalescent rehabilitation in patients with ischemic stroke: a retrospective study.

ABSTRACTCilostazol is a phosphodiesterase III-inhibiting antiplatelet agent that is often used to prevent stroke and peripheral artery disease, and its administration has shown significant improvements for cognitive impairment. We investigate the potential of cilostazol for reducing or restoring cognitive decline during convalescent rehabilitation in patients with non-cardioembolic ischemic stroke. The study sample included 371 consecutive patients with lacunar (n = 44) and atherothrombosis (n = 327) subtypes of non-cardioembolic ischemic stroke (224 men and 147 women; mean age, 72.9 ± 8.1 years) who were required for inpatient convalescent rehabilitation. Their medical records were retrospectively surveyed to identify those who had received cilostazol (n = 101). Patients were grouped based on cilostazol condition, and Functional Independence Measure (FIM) scores (total and motor or cognitive subtest scores) were assessed both at admission and discharge. The gain and efficiency in FIM cognitive scores from admission to discharge were significantly higher in patients who received cilostazol than those who did not (p = 0.047 and p = 0.035, respectively); we found no significant differences in other clinical factors or scores. Multiple linear regression analysis confirmed that cilostazol was a significant factor in FIM cognitive scores at discharge (β = 0.041, B = 0.682, p = 0.045); the two tested dosages were not significantly different (100 mg/day, n = 43; 200 mg/day, n = 58). Cilostazol can potentially improve cognitive function during convalescent rehabilitation of patients with non-cardioembolic ischemic stroke, although another research must be needed to confirm this potential.

Cystatin C as a predictor for carotid artery steno-occlusive disease in non-cardioembolic ischemic stroke

BackgroundStroke is the third leading cause of death in developed nations. Ultrasonography (US) of the carotid arteries is the modality of choice for diagnosis and monitoring of cases of atheromatous disease. Cystatin C (CysC) is a risk factor for cerebrovascular and cardiovascular disease.ObjectivesTo detect the association of serum CysC levels with acute ischemic stroke, the correlation of its levels with stroke severity, and the association between CysC levels with extra- and intracranial stenosis.MethodsCase-control study was conducted on 66 subjects, 33 patients within the first week of stroke onset with age range from 40 to 75 years, and 33 control healthy subjects with matched age and sex. All subjects underwent complete neurological examination, Extra- and transcranial duplex, CT brain, routine laboratory work-up, and serum CysC.ResultsSerum CysC levels were significantly raised in patients with acute ischemic stroke compared to controls. CysC levels were higher in patients with extracranial stenosis than in those with intracranial stenosis. Moreover, extracranial stenosis > 50% has higher levels of CysC. Serum CysC level showed a significant correlation with National Institutes of Health Stroke Scale (NIHSS) and intima-media thickness (IMT).ConclusionSerum CysC can be used as a marker for acute atherosclerotic ischemic stroke and stroke severity. High-grade extracranial stenosis has the highest level of CysC.

Dual antiplatelet therapy using cilostazol for secondary prevention in patients with high-risk ischaemic stroke in Japan: a multicentre, open-label, randomised controlled trial

Although dual antiplatelet therapy with aspirin and clopidogrel reduces early recurrence of ischaemic stroke, with long-term use this type of therapy is no longer effective and the risk of bleeding increases. Given that cilostazol prevents stroke recurrence without increasing the incidence of serious bleeding compared with aspirin, we aimed to establish whether dual antiplatelet therapy involving cilostazol is safe and appropriate for long-term use. In a multicentre, open-label, randomised controlled trial across 292 hospitals in Japan, patients with high-risk non-cardioembolic ischaemic stroke identified on MRI were randomly assigned to two groups in a 1:1 ratio to receive monotherapy with either oral aspirin (81 or 100 mg, once per day) or clopidogrel (50 or 75 mg, once per day) alone, or a combination of cilostazol (100 mg, twice per day) with aspirin or clopidogrel. Randomisation was done centrally (using block randomisation with a block size of six per each participating hospital) through a web-based registration system and was done by EPS Corporation. The patients were required to have at least 50% stenosis of a major intracranial or extracranial artery or two or more of the vascular risk factors. Trial medication was continued for half a year or longer, for a maximum of 3·5 years. The primary efficacy outcome was the rate of first recurrence of symptomatic ischaemic stroke. Safety outcomes were severe or life-threatening bleeding; any adverse events; serious adverse events; and any bleeding events. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the as-treated population. This trial was registered with ClinicalTrials.gov (number NCT01995370) and UMIN Clinical Trials Registry (number 000012180). Participants were recruited from Dec 13, 2013, to March 31, 2017. 932 patients assigned to the dual therapy group and 947 patients assigned to the monotherapy group were included in the intention-to-treat analysis. The trial was stopped after the enrolment of 1884 patients of an anticipated 4000 patients because of the delay in recruitment. Ischaemic stroke recurred in 29 (3%) of 932 patients (annualised rate 2·2%) on dual therapy including cilostazol and 64 (7%) of 947 patients (annualised rate 4·5%) on monotherapy during a median 1·4 years follow-up (hazard ratio [HR] 0·49, 95% CI 0·31-0·76, p=0·0010). Severe or life-threatening bleeding occurred in eight patients (annualised rate 0·6%) on dual therapy and 13 patients (annualised rate 0·9%) on monotherapy (HR 0·66, 95% CI 0·27-1·60, p=0·35). Occurrence of any type of adverse event was similar between the groups (255 [28%] of 910 patients in the dual therapy group vs 219 [24%] of 921 patients in the monotherapy group); as was occurrence of serious adverse events (87 [10%] vs 142 [15%]) and bleeding events (38 [4%] vs 33 [4%]). Gastrointestinal bleeding, which affected nine (<1%) of 910 patients in the monotherapy group and nine (<1%) of 921 patients in the dual therapy group, was the most common type of bleeding. The combination of cilostazol with aspirin or clopidogrel had a reduced incidence of ischaemic stroke recurrence and a similar risk of severe or life-threatening bleeding compared with treatment with aspirin or clopidogrel alone in patients at high risk for recurrent ischaemic stroke. Otsuka Pharmaceutical.