Efficacy and safety of oxiracetam in patients with vascular cognitive impairment: A multicenter, randomized, double-blinded, placebo-controlled, phase IV clinical trial.

BACKGROUND: Oxiracetam may have a modest effect on preventing cognitive decline. Exercise can also enhance cognitive function. This trial aims to investigate the effect of oxiracetam on post-stroke cognitive impairment and explore whether this effect is modified by exercise. Furthermore, the mechanisms that mediate this effect will be investigated through a neural network analysis. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Patients who complained of cognitive decline 3 months after stroke and had a high risk of cognitive decline were eligible. Patients were randomly assigned to receive either 800 mg of oxiracetam or placebo twice daily for 36 weeks. After randomization, a predetermined exercise protocol was provided to each participant, and the degree of physical activity was assessed using wrist actigraphy at 4, 12, 24, and 36 weeks. Resting-state functional MRI was obtained in baseline and 36-week follow-up. Co-primary endpoints are changes in the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Secondary endpoints include changes in the NINDS-CSN VCIHS-Neuropsychology Protocol, Euro QoL, patient's global assessment, and functional network connectivity. If there is a significant difference in physical activity between the two groups, the interaction effect between physical activity and the treatment group will be examined. A total of 500 patients were enrolled from February 2018, and the last patient's final follow-up was completed in September 2022. CONCLUSION: This trial is meaningful not only to prove the efficacy of oxiracetam, but also evaluate whether exercise can modify the effects of medication and how cognitive function can be restored. Trial registrationhttp://cris.nih.go.kr (KCT0005137).

Optimal use of antithrombotic agents in ischemic stroke with atrial fibrillation and large artery atherosclerosis.

BACKGROUND: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown. AIMS: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes. METHODS: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores. RESULTS: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23-0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19-0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31-21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups. CONCLUSION: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

Apixaban for Secondary Stroke Prevention: Coexistant Cerebral Atherosclerosis May Increase Recurrent Strokes.

BACKGROUND AND PURPOSE: Oral anticoagulants are needed in stroke patients with atrial fibrillation (AF) for the prevention of recurrent stroke. However, the risk of major events or bleeding may be greater in stroke patients than in those without, because the presence of cerebral atherosclerosis or small vessel disease may increase these risks. This study aimed to investigate the outcomes of apixaban-treated stroke patients with AF and assess whether these factors are associated with the outcome. METHODS: This was a sub-analysis of stroke patients with AF enrolled in a prospective, open-label, multicenter, post-marketing surveillance study in South Korea, who were treated with apixaban and underwent magnetic resonance imaging (MRI) (Clinical trial registration: NCT01885598). RESULTS: A total of 651 patients (mean age, 72.5±8.7 years) received apixaban for a mean duration of 82.7±37.4 weeks. Fifty-three bleeding events occurred in 39 patients (6.0%), and 10 (1.5%) experienced major bleeding. Seventeen patients (2.6%) had major events (stroke, n=15, 2.3%; all ischemic), systemic embolism (n=1, 0.2%), and death (n=3, 0.5%). MRI data showed no significant association between white matter ischemic changes and microbleeds, and major events or bleeding. Patients with cerebral atherosclerotic lesions had a higher rate of major events than those without (4.6% [n=10/219] vs. 1.7% [n=7/409], P=0.0357), which partly explains the increased prevalence of major outcomes in this group versus patients without stroke (0.7%, P=0.0002). CONCLUSIONS: Apixaban is generally safe for patients with ischemic stroke. Increased primary outcomes in stroke patients may in part be attributed to the presence of cerebral atherosclerotic lesions, suggesting that further studies are needed to establish therapeutic strategies in this population.

Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study.

BACKGROUND AND PURPOSE: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. METHODS: This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). RESULTS: Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. CONCLUSIONS: Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.

Comparison of the Solitaire and Trevo Stents for Endovascular Treatment of Acute Ischemic Stroke: A Single.Center Experience.

AIMS: Limited studies have compared the effectiveness of Solitaire and Trevo stentrievers for endovascular thrombectomy to achieve recanalization and improve functional outcomes of patients with acute ischemic stroke. Therefore, we compared the safety and efficacy of the two stents during endovascular thrombectomy for patients with acute ischemic stroke. MATERIALS AND METHODS: This study included 130 patients who underwent endovascular thrombectomy using either the Trevo (n = 51) or the Solitaire (n = 79) stent for anterior circulation acute ischemic stroke. Recanalization was classified using thrombolysis in cerebral infarction (TICI) grading. Efficacy and safety of the devices during endovascular thrombectomy were analyzed by evaluating the rate of good recanalization after the first pass, clot retrieval rate, final recanalization grade, use of rescue treatment, recanalization time, and hemorrhagic and thromboembolic complications. RESULTS: Overall, good recanalization (TICI grades 2b and 3) was achieved (Solitaire: n = 57, 72.2%; Trevo: n = 46, 90.2%) (P = 0.01). The rate of good recanalization after the first pass and clot retrieval rate were similar between groups; however, the use of rescue treatment was more frequent in the Solitaire group. Recanalization time was shorter in the Trevo group. The good clinical outcome rate was higher in the Trevo group but not statistically significantly. The rates of symptomatic hemorrhage and thromboembolism were not significantly different between groups. CONCLUSION: The Trevo stent achieved more successful recanalization with less need for rescue treatment and less time for recanalization than the Solitaire stent. There was no statistically significant difference in the clinical outcomes.

Changes in High-Density Lipoprotein Cholesterol and Risks of Cardiovascular Events: A Post Hoc Analysis from the PICASSO Trial.

BACKGROUND AND PURPOSE: Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study. METHODS: Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm. RESULTS: One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, P<0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, P<0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint. CONCLUSIONS: Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.

Safety and Efficacy of Otaplimastat in Patients with Acute Ischemic Stroke Requiring tPA (SAFE-TPA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study.

OBJECTIVE: Otaplimastat is a neuroprotectant that inhibits matrix metalloprotease pathway, and reduces edema and intracerebral hemorrhage induced by recombinant tissue plasminogen activator (rtPA) in animal stroke models. We aimed to assess the safety and efficacy of otaplimastat in patients receiving rtPA. METHODS: This was a phase 2, 2-part, multicenter trial in stroke patients (19-80 years old) receiving rtPA. Intravenous otaplimastat was administered <30 minutes after rtPA. Stage 1 was a single-arm, open-label safety study in 11 patients. Otaplimastat 80 mg was administered twice daily for 3 days. Stage 2 was a randomized, double-blind, placebo-controlled study involving 69 patients, assigned (1:1:1) to otaplimastat 40 mg, otaplimastat 80 mg, or a placebo. The primary endpoint was the occurrence of parenchymal hematoma (PH) on day 1. Secondary endpoints included serious adverse events (SAEs), mortality, and modified Rankin scale (mRS) distribution at 90 days (clinicaltrials.gov identifier: NCT02787278). RESULTS: No safety issues were encountered in stage 1. The incidence of PH during stage 2 was comparable: 0 of 22 with the placebo, 0 of 22 with otaplimastat 40 mg, and 1 of 21 with the 80 mg dose. No differences in SAEs (13%, 17%, 14%) or death (8.3%, 4.2%, 4.8%) were observed among the 3 groups. Three adverse events (chills, muscle rigidity, hepatotoxicity) were judged to be related to otaplimastat. INTERPRETATION: Intravenous otaplimastat adjunctive therapy in patients receiving rtPA is feasible and generally safe. The functional efficacy of otaplimastat needs to be investigated with further large trials. ANN NEUROL 2020;87:233-245.

Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial.

Background and Purpose- Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods- Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results- Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke (P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01-0.61]; P=0.01). A marginal interaction between treatment group and white matter change on any stroke (P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13-0.97]; P=0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29-0.92]; P=0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions- Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.

Therapeutic-induced hypertension in patients with noncardioembolic acute stroke.

OBJECTIVE: To evaluate the safety and efficacy of induced hypertension in patients with acute ischemic stroke. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICALTRIALSGOV IDENTIFIER: NCT01600235. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with acute ischemic stroke, therapeutic-induced hypertension increases the probability of early neurologic improvement.

Blood Pressure Variability Is Associated With White Matter Lesion Growth in Intracranial Atherosclerosis.

BACKGROUND: High blood pressure variability (BPV) is associated with recurrent stroke. We investigated the association between BPV, new ischemic lesions (NILs), and white matter lesion (WML) growth in patients with ischemic stroke due to intracranial atherosclerosis (ICAS). METHODS: This study was performed as a post-hoc analysis of the STABLE-ICAS trial, which enrolled subacute ischemic stroke patients with symptomatic ICAS (>50% stenosis) and hypertension. BPV was measured at the office (visit by visit) and at home (day by day). Patients were divided into 3 groups (tertiles) according to their home BPV. WML growth and the occurrence of NILs were compared among the 3 groups. Multivariable analyses were performed to identify the independent risk factors of WML growth and NILs. RESULTS: Of the 111 enrolled patients, 69 patients (67.6%) demonstrated WML growth and 15 patients (13.7%) had NILs. Patients with higher BPV demonstrated a more WML growth (50% vs. 61.8% vs. 83.8; P = 0.02, by tertiles) and more NILs (5.4% vs. 5.4% vs. 29.7%; P = 0.002, by tertiles). In multivariable analyses, old age [odds ratio (OR) = 1.052 (95% confidence interval (CI) = 1.005-1.101); P = 0.03] and home BPV [OR = 1.149 (95% CI = 1.013-1.304); P = 0.02] were independently associated with WML growth. Low mean diastolic blood pressure [OR = 0.913 (95% CI = 0.874-0.984); P = 0.02] and high home BPV [OR = 1.287 (95% CI = 1.086-1.526); P = 0.004] were independently associated with NILs at follow-up. CONCLUSIONS: High BPV is associated with WML growth and NIL in ischemic stroke patients with symptomatic ICAS. BPV monitoring at home may be helpful.

Executive Summary of Stroke Statistics in Korea 2018: A Report from the Epidemiology Research Council of the Korean Stroke Society.

Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched the "Stroke Statistics in Korea" project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.

Medication Adherence of Statin Users after Acute Ischemic Stroke.

Although statins are established therapy for the secondary prevention of ischemic stroke, factors associated with adherence to statin treatment following ischemic stroke are not well known. To address this, we assessed the 6-month statin adherence using 8-item Morisky Medication Adherence Scale-8 in patients with acute ischemic stroke. Of 991 patients, 65.6% were adherent to statin at 6-month after discharge. Multiple logistic regression analysis showed that patients' awareness of hyperlipidemia (OR 1.62; 95% CI 1.07-2.43), large artery stroke subtype (versus non-large artery stroke, OR 1.79; 95% CI 1.19-2.68), and alcohol drinking habits (OR 1.64; 95% CI 1.06-2.53) were positively associated, while high statin dose (versus low dose, OR 0.6; 95% CI 0.40-0.90) and higher daily number of medication pills (OR 0.93; 95% CI 0.88-0.97) were found to have a negative association with self-reported good adherence to statin medication after acute ischemic stroke. However, stroke severity and diagnosis of hyperlipidemia were not associated with adherence. These results suggest that educational and motivational interventions may enhance statin adherence because modifiable factors were associated with statin adherence.

Prediction of hemorrhagic transformation in patients with mild atrial fibrillation-associated stroke treated with early anticoagulation: post hoc analysis of the Triple AXEL Trial.

OBJECTIVES: To investigate the predictors of hemorrhagic transformation (HT) in patients with mild atrial fibrillation-related stroke who were treated with early anticoagulation. We conducted a post-hoc subgroup analysis from Acute Cerebral Infarction Patients with Non-valvular Atrial Fibrillation (Triple AXEL) study. PATIENTS AND METHODS: The Triple AXEL study was a randomized, multicenter, open-label, blinded end-point evaluation, comparative phase 2 trial. To identify the relationship between the type of HT and risk factors. We analyzed various factors using data from the Triple AXEL study, such as sex, history of hypertension, diabetes, microbleeds, concomitant antiplatelet use, initial infarction volume, initial infarction location, and new intracranial hemorrhage on follow-up gradient recalled echo or susceptibility-weighted imaging. RESULTS: We analyzed various factors by dividing patients into a new HT group and a no HT group. No correlation was found between HT and risk factors that were significantly associated with HT, including age, sex, history of hypertension, diabetes, microbleeds, concomitant antiplatelet use, and initial infarction volume. When the initial infarction was classified into anterior circulation infarction (ACI) and posterior circulation infarction (PCI), the occurrence of new HT was significantly more associated with PCI than with ACI (57.6% vs 24.0%, P = 0.001). Multivariate logistic regression analysis was performed using HT as a response variable. Only the location of initial infarction according to the vascular territory contributed to the increased risk of HT (OR2.3, 95%CI1.33-3.91, P = 0.003). CONCLUSION: PCI is a very important independent risk factor for HT in patients with mild AF-related stroke treated with early anticoagulation.

Intensive blood pressure control may not be safe in subacute ischemic stroke by intracranial atherosclerosis: a result of randomized trial.

OBJECTIVE: Current guideline recommends intensive blood pressure (BP) control in hypertensive patients, but the appropriate target BP level after ischemic stroke due to intracranial atherosclerotic stenosis remains uncertain. METHODS: In this randomized, single-blinded trial, patients with symptomatic internal carotid or middle cerebral artery steno-occlusion (>50%) within 7-42 days after index stroke received intensive (target SBP < 120 mmHg) or modest (target SBP < 140 mmHg) BP control from April 2010 to December 2012. The primary outcome was the change in ischemic lesion volume in white matter lesions at the whole forebrain between baseline and 24 weeks as measured from fluid attenuation inversion recovery (FLAIR) images, which was tested in noninferiority test (noninferiority margin of 3 cm). RESULTS: Among 132 patients, follow-up FLAIR images were available in 111 (59 in the intensive and 52 in the moderate BP control groups). After 24 weeks, the SBP in the intensive group was significantly lower (124.6 ±â€Š10.5 mmHg) than in the modest group (132.3 ±â€Š10.6 mmHg). The ischemic lesion volume increased more in the intensive group (4.9 ±â€Š18.3 cm) than the modest group (2.2 ±â€Š8.2 cm), which failed to prove noninferiority. The frequency of new ischemic lesions on 24-week FLAIR images was nonsignificantly higher in the intensive group than the modest group [10 (16.9%) vs. 5 (9.6%), respectively; P = 0.26)]. Only one recurrent stroke developed during the study period in each group. CONCLUSION: Intensive BP control in intracranial atherosclerotic stenosis patients failed to prove noninferiority compared with modest BP control, and may increase ischemic lesion volume in the subacute stage.

Low- versus Standard-Dose Intravenous Alteplase in the Context of Bridging Therapy for Acute Ischemic Stroke: A Korean ENCHANTED Study.

BACKGROUND AND PURPOSE: Following the positive results from recent trials on endovascular therapy (EVT), bridging therapy (intravenous alteplase plus EVT) is increasingly being used for the treatment of acute ischemic stroke. However, the optimal dose of intravenous alteplase remains unknown in centers where bridging therapy is actively performed. The optimal dose for eventual recanalization and positive clinical outcomes in patients receiving bridging therapy also remains unknown. METHODS: In this prospective Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) sub-study, we explored the outcomes following treatment with two different doses (low- [0.6 mg/kg] or standard-dose [0.9 mg/kg]) of intravenous alteplase across 12 Korean centers where EVT is actively performed. The primary endpoint was a favorable outcome at 90 days (modified Rankin Scale scores 0 to 1). Secondary endpoints included symptomatic intracerebral hemorrhage (ICH) in all patients, and the recanalization rate and favorable outcome in patients who underwent cerebral angiography for EVT (ClinicalTrials.gov, number NCT01422616). RESULTS: Of 351 patients, the primary outcome occurred in 46% of patients in both the standard-(80/173) and low-dose (81/178) groups (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.72 to 1.81; P=0.582), although ICHs tended to occur more frequently in the standard-dose group (8% vs. 3%, P=0.056). Of the 67 patients who underwent cerebral angiography, there was no significant difference in favorable functional outcome between the standard- and low-dose groups (39% vs. 21%; OR, 2.39; 95% CI, 0.73 to 7.78; P=0.149). CONCLUSIONS: There was no difference in functional outcome between the patients receiving different doses of alteplase in centers actively performing bridging therapy.

An Unusual Case of Bilateral Meralgia Paresthetica Following Femoral Cannulations.

Meralgia paresthetica (MP) is a sensory mononeuropathy of the lateral femoral cutaneous nerve (LFCN). MP has rarely been reported after a femoral intervention approach. We report a case of bilateral meralgia paresthetica following bilateral femoral cannulation. A 64-year-old male received cardiac catheterization and treatment via a bilateral femoral vein. After cardiac catheterization, the patient presented with paresthesia in the anterolateral aspect of the bilateral thigh. After performing nerve conduction studies and electromyography, he was diagnosed as MP. Although a bilateral LFCN lesion following a femoral approach is very rare, MP might require caution regarding potential variations in LFCN when performing the femoral approach.

Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation-Related Mild Ischemic Stroke: A Randomized Clinical Trial.

Importance: In atrial fibrillation (AF)-related acute ischemic stroke, the optimal oral anticoagulation strategy remains unclear. Objective: To test whether rivaroxaban or warfarin sodium is safer and more effective for preventing early recurrent stroke in patients with AF-related acute ischemic stroke. Design, Setting, and Participants: A randomized, multicenter, open-label, blinded end point evaluation, comparative phase 2 trial was conducted from April 28, 2014, to December 7, 2015, at 14 academic medical centers in South Korea among patients with mild AF-related stroke within the previous 5 days who were deemed suitable for early anticoagulation. Analysis was performed on a modified intent-to-treat basis. Interventions: Participants were randomized 1:1 to receive rivaroxaban, 10 mg/d for 5 days followed by 15 or 20 mg/d, or warfarin with a target international normalized ratio of 2.0-3.0, for 4 weeks. Main Outcomes and Measures: The primary end point was the composite of new ischemic lesion or new intracranial hemorrhage seen on results of magnetic resonance imaging at 4 weeks. Primary analysis was performed in patients who received at least 1 dose of study medications and completed follow-up magnetic resonance imaging. Key secondary end points were individual components of the primary end point and hospitalization length. Results: Of 195 patients randomized, 183 individuals (76 women and 107 men; mean [SD] age, 70.4 [10.4] years) completed magnetic resonance imaging follow-up and were included in the primary end point analysis. The rivaroxaban group (n = 95) and warfarin group (n = 88) showed no differences in the primary end point (47 [49.5%] vs 48 [54.5%]; relative risk, 0.91; 95% CI, 0.69-1.20; P = .49) or its individual components (new ischemic lesion: 28 [29.5%] vs 31 of 87 [35.6%]; relative risk, 0.83; 95% CI, 0.54-1.26; P = .38; new intracranial hemorrhage: 30 [31.6%] vs 25 of 87 [28.7%]; relative risk, 1.10; 95% CI, 0.70-1.71; P = .68). Each group had 1 clinical ischemic stroke, and all new intracranial hemorrhages were asymptomatic hemorrhagic transformations. Hospitalization length was reduced with rivaroxaban compared with warfarin (median, 4.0 days [interquartile range, 2.0-6.0 days] vs 6.0 days [interquartile range, 4.0-8.0]; P < .001). Conclusions and Relevance: In mild AF-related acute ischemic stroke, rivaroxaban and warfarin had comparable safety and efficacy. Trial Registration: clinicaltrials.gov Identifier: NCT02042534.

Extremely Small Pseudoparamagnetic Iron Oxide Nanoparticle as a Novel Blood Pool T1 Magnetic Resonance Contrast Agent for 3 T Whole-Heart Coronary Angiography in Canines: Comparison With Gadoterate Meglumine.

OBJECTIVE: The aim of this study was to evaluate an extremely small pseudoparamagnetic iron oxide nanoparticle (ESPIO), KEG3, as a potential blood pool agent in 3 T coronary magnetic resonance angiography (MRA) in canine models and compare its efficacy to that of a gadolinium-based contrast agent. MATERIALS AND METHODS: Nine mongrel dogs were subjected to whole-heart coronary MRA in 2 separate sessions at 7-day intervals with a 3 T scanner using the FLASH sequence with either gadoterate meglumine (Gd-DOTA) or the ESPIO (KEG3). Coronary MRA was performed twice at each MR examination: the first scan during the administration of the contrast agent and the subsequent second scan at 15 minutes after contrast injection. Objective measurements of the Gd-DOTA and ESPIO images, including the signal-to-noise ratios (SNRs) for the coronary arteries and cardiac veins, contrast-to-noise ratios (CNRs) between the vessels and fat (CNRfat) and the vessels and the myocardium (CNRmyocardium), and subjective image quality scores on a 4-point scale were evaluated and compared. RESULTS: The mean SNRs and CNRs of all vascular regions in the ESPIO images were similar to those of the corresponding regions in the Gd-DOTA images in the first scan (98.1 ± 32.5 vs 79.1 ± 38.4 for SNR of coronary arteries, P = 0.3; 74.2 ± 30.1 vs 61.4 ± 38.5 for CNR, P = 0.7) and more than 2 times higher than the latter in the second scan (95.2 ± 31.3 vs 32.1 ± 8.1 for SNR of coronary arteries, P = 0.008; 76.1 ± 35.8 vs 17.6 ± 19.2 for CNR, P 0.008). Similarly, the mean values of the subjective measurements of the ESPIO images were similar to those of the Gd-DOTA images (3.9 ± 0.3 vs 3.3 ± 0.8 for coronary arteries, P = 0.1) in the first scan and significantly better than the latter in the second scan (3.9 ± 0.2 vs 2.1 ± 0.6 for coronary arteries, P = 0.007). CONCLUSIONS: The experimental blood pool agent KEG3 offers equivalent image quality for whole-heart coronary MRA at 3 T upon contrast administration and persistent better quality in the subsequent scans, compared with a traditional extracellular gadolinium-based contrast agent.

Recurrent Ischemic Lesions After Acute Atherothrombotic Stroke: Clopidogrel Plus Aspirin Versus Aspirin Alone.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke caused by large artery atherosclerosis, clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia. However, there is no clear evidence. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel (75 mg/d without loading dose) plus aspirin (300-mg loading followed by 100 mg/d) or to aspirin alone (300-mg loading followed by 100 mg/d) for 30 days. The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days. Secondary outcomes were 30-day functional disability, clinical stroke recurrence, and composite of major vascular events. Safety outcome was any bleeding. RESULTS: Of 358 patients enrolled, 334 (167 in each group) completed follow-up magnetic resonance imaging. The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups (36.5% versus 35.9%; relative risk, 1.02; 95% confidence interval, 0.77-1.35; P=0.91). Of the recurrent ischemic lesions, 94.2% were clinically asymptomatic. There were no differences in secondary outcomes between the 2 groups. Any bleeding were more frequent in the combination group than in the aspirin monotherapy group, but the difference was not significant (16.7% versus 10.7%; P=0.11). One hemorrhagic stroke occurred in the clopidogrel plus aspirin group. CONCLUSIONS: Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00814268.