Risk Of Recurrent Ischemic Stroke Research Articles

Silent new ischemic lesions after index stroke and the risk of future clinical recurrent stroke.

To test whether a silent new ischemic lesion (SNIL) on MRI after stroke predicted future recurrent ischemic stroke or vascular events. In this prospective study, we analyzed data from patients presenting with acute ischemic stroke who underwent MRI <24 hours and 5 and 30 days after symptom onset. The presence of a SNIL at 5 (5D-SNIL) and 30 (30D-SNIL) days was determined on diffusion-weighted and fluid-attenuated inversion recovery images. Patients were contacted every 3-6 months to identify recurrent clinical events. The log-rank test and Cox proportional hazard model were used to estimate the hazard ratio of recurrent ischemic stroke and composites of recurrent ischemic stroke, transient ischemic attack, acute coronary syndrome, and vascular death. The 5D- and 30D-SNILs were found in 24.4% (66/270) and 7.4% (19/256) of patients. During the 5-year follow-up, clinical events were observed in 42 patients (15.6%). The 5D- and 30D-SNIL independently predicted recurrent ischemic stroke (hazard ratio [95% confidence interval] 2.9 [1.3-6.4] and 9.6 [4.1-22.1], respectively) and composite vascular events (2.4 [1.3-4.5] and 6.1 [3.1-12.4], respectively). Patients with a SNIL within the first few weeks after index stroke have an increased risk of recurrent ischemic stroke or vascular events. The presence of a SNIL on MRI could serve as a surrogate endpoint for clinical recurrence in secondary prevention clinical trials.

Association of CYP2C19 gene polymorphisms with long-term recurrent risk of ischemic stroke among ethnic Han Chinese from Fujian

To assess the association of genetic polymorphisms of CYP2C19*2,*3,*17 with the recurrence risk of ischemic stroke during clopidogrel prevention in ethnic Han Chinese from Fujian Province. Clinical data of 985 patients with acute ischemic stroke was collected. After 1 year postdischarge follow-up evaluations, only 114 patients with persistence of clopidogrel were enrolled. CYP2C19 genetic polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)and direct sequencing ,then we analysis the correlation between polymorphisms and the recurrence of stroke. Among the 114 patients, 23 had a second onset whilst receiving clopidogrel treatment. During the antiplatelet therapy with clopidogrel, carriers of CYP2C19 poor metabolizer (CYP2C19*2/*2 or *2/*3) had a higher rate of recurrent stroke compared with extensive metabolizers (CYP2C19*1/*1) (OR=4.71, 95%CI: 1.18-18.80, P<0.05). Carriers of CYP2C19 *2 mutant allele had increased recurrence compared with those carrying none loss-of-function allele (OR=2.31, 95%CI: 1.20-4.46, P<0.05). The rate of recurrent stroke in those carrying homozygous mutant *2 allele (CYP2C19*2/*2) was 6.14 times greater than the rate of wild-type homozygotes (CYP2C19*1/*1) (95%CI: 1.54-24.54, P<0.05). Patients with previous stroke history had increased risk of recurrence (OR= 4.146, 95%CI: 1.259-13.655, P<0.05). However, CYP2C19*17 was not detected in the group. For ethnic Han Chinese patients receiving clopidogrel treatment, carriers of poor metabolizer or homozygous mutant *2 allele (CYP2C19*2/*2) have a higher risk of recurrent stroke. The CYP2C19 *2 allele is an independent risk factor for recurrent stroke. Those with previous history of stroke are more prone to the recurrence.

Elevated Total Homocysteine Levels in Acute Ischemic Stroke Are Associated With Long-Term Mortality.

Background and Purpose—Total homocysteine (tHcy) levels are associated with secondary vascular events and mortality after stroke. The aim of this study was to investigate whether tHcy levels in the acute phase of a stroke contribute to the recurrence of cerebro-cardiovascular events and mortality.Methods—A total of 3799 patients were recruited after hospital admission for acute ischemic stroke. Levels of tHcy were measured within 24 hours after primary admission. Patients were followed for a median of 48 months.Results—During the follow-up period, 233 (6.1%) patients died. After adjustment for age, smoking status, diabetes mellitus, and other cardiovascular risk factors, patients in the highest tHcy quartile (>18.6 μmol/L) had a 1.61-fold increased risk of death (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.03–2.53) compared with patients in the lowest quartile (≤10 μmol/L). Further subgroup analysis showed that this correlation was only significant in the large-artery atherosclerosis stroke subtype (adjusted HR, 1.80; 95% CI, 1.05–3.07); this correlation was not significant in the small-vessel occlusion subtype (adjusted HR, 0.80; 95% CI, 0.30–2.12). The risk of stroke-related mortality was 2.27-fold higher for patients in the third tHcy quartile (adjusted HR, 2.27; 95% CI, 1.06–4.86) and 2.15-fold more likely for patients in the fourth quartile (adjusted HR, 2.15; 95% CI, 1.01–4.63) than for patients in the lowest tHcy quartile. The risk of cardiovascular-related mortality and the risk of recurrent ischemic stroke were not associated with tHcy levels.Conclusions—Our findings suggest that elevated tHcy levels in the acute phase of an ischemic stroke can predict mortality, especially in stroke patients with the large-vessel atherosclerosis subtype.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

English

Patients surviving with a stroke have an increased risk for recurrent stroke. Clopidogrel is widely used to prevent recurrent stroke. However, clopidogrel may cause gastrointestinal bleeding (GIB). Therefore, proton pump inhibitors (PPIs) is recommended to reduce the side effect of clopidogrel. Unfortunately, these both drugs are metabolized in the liver by the same enzyme i.e. cytochrome P4502C19 (CYP219) that may reduce the effect of clopidogrel. The aim of this study was to evaluate the influence of PPIs on the effect of clopidogrel in the prevention of recurrent stroke. It was a hospital-based case control study conducted in Bethesda Private Hospital, Yogyakarta involving 392 patients with recurrent stroke as cases and 784 patients with first-ever stroke as controls. The exposure of PPIs during clopidogrel therapy on both cases and controls groups were recorded from prescription records for at least six months before index date. The duration of PPIs exposure were categorized as current expoure (less than two months before the index date) and recent exposure (2-6 months before the index date). The result showed there was no influence of PPIs exposure on the effect of clopidogrel on the risk of recurrent ischemic stroke (OR: 1.00; 95% CI: 0.56-1.79). Moreover, the current use of PPIs and clopidogrel could decrease the risk of recurrent ischemic stroke (OR: 0.04; 95% CI: 0.01-0.41). In conclusion, there is no association between PPI exposure and the risk of recurrent stroke in patients receiving clopidogrel.

Prediction factors of recurrent ischemic events in one year after minor stroke.

BackgroundThe risk of a subsequent stroke following a minor stroke is high. However, there are no effective rating scales to predict recurrent stroke following a minor one. Therefore, we assessed the risk factors associated with recurrent ischemic stroke or transient ischemic attack (TIA) within one year of minor stroke onset in order to identify possible risk factors.MethodsEight hundred and sixty-three non-cardioembolic ischemic stroke patients in the Chinese IntraCranial AtheroSclerosis Study that presented with minor stroke, defined as an admission National Institutes of Health stroke scale (NIHSS) score of ≤3, were consecutively enrolled in our study. Clinical information and imaging features upon admission, and any recurrent ischemic stroke or TIA within one year was recorded. Cox regression was used to identify risk factors associated with recurrent ischemic stroke or TIA within the year following stroke onset.ResultsA total of 50 patients (6.1%) experienced recurrent ischemic stroke or TIA within one year of minor stroke onset. Multivariate Cox regression model identified lower admission NIHSS score (HR, 1.75; 95% CI, 1.32 to 2.33; P<0.0001), history of coronary heart disease (HR, 2.62; 95% CI, 1.17 to 5.86; P = 0.02), severe stenosis or occlusion of large cerebral artery (HR, 4.68; 95% CI, 1.87 to 11.7; P = 0.001), and multiple acute cerebral infarcts (HR, 2.61; 95% CI, 1.01 to 6.80; P = 0.05) as independent risk factors for recurrent ischemic stroke or TIA within one year.ConclusionsSome minor stroke patients are at higher risk for recurrent ischemic stroke or TIA. Urgent and intensified therapy may be reasonable in these patients.

D-dimer for prediction of long-term outcome in cryptogenic stroke patients with patent foramen ovale.

Patent foramen ovale (PFO) is a potential cause of cryptogenic stroke, given the possibility of paradoxical embolism from venous to systemic circulation. D-dimer level is used to screen venous thrombosis. We investigated the risk of embolism and mortality according to the presence of PFO and D-dimer levels in cryptogenic stroke patients. A total of 570 first-ever cryptogenic stroke patients who underwent transesophageal echocardiography were included in this study. D-dimer was assessed using latex agglutination assay during admission. The association of long-term outcomes with the presence of PFO and D-dimer levels was investigated. PFO was detected in 241 patients (42.3 %). During a mean 34.0 ± 22.8 months of follow-up, all-cause death occurred in 58 (10.2 %) patients, ischaemic stroke in 33 (5.8 %), and pulmonary thromboembolism in 6 (1.1 %). Multivariate Cox regression analysis showed that a D-dimer level of > 1,000 ng/ml was an independent predictor for recurrent ischaemic stroke in patients with PFO (hazard ratio 5.341, 95 % confidence interval 1.648-17.309, p=0.005), but not in those without PFO. However, in patients without PFO, a D-dimer level of > 1,000 ng/ml was independently related with all-cause mortality. The risk of pulmonary thromboembolism tended to be high in patients with high D-dimer levels, regardless of PFO. Elevated D-dimer levels in cryptogenic stroke were predictive of the long-term outcome, which differed according to the presence of PFO. The coexistence of PFO and a high D-dimer level increased the risk of recurrent ischaemic stroke. The D-dimer test in cryptogenic stroke patients may be useful for predicting outcomes and deciding treatment strategy.

Postthrombolytic Antiplatelet Use for Patients with Intercerebral Hemorrhage without Extensive Parenchymal Involvement Does Not Worsen Outcome.

Background and PurposeIt is unclear whether postthrombolytic antiplatelet (AP) therapy after thrombolytic-related hemorrhage without extensive parenchymal involvement (THEPI) affects the clinical outcome. This study explored whether AP administration in patients with THEPI affects short- and long-term outcomes.MethodsAll of the data for this study were collected from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) registry. Patients with THEPI were assigned to either the AP (AP therapy should be commenced 24 h after intravenous thrombolysis) or AP-naïve groups. THEPI was defined according to European-Australasian Acute Stroke Study II criteria. The 90-day functional outcome, 7-day National Institutes of Health Stroke Scale (NIHSS) score, and 7-day and 90-day mortalities were compared between the AP and AP-naïve groups. Logistic regression analysis was used to evaluate the effects of AP therapy on the short- and long-term clinical outcomes.ResultsOf the 928 patients enrolled from those in the TIMS-China registry (n=1,440), 89 (9.6%) had nonsymptomatic intracerebral hemorrhage (ICH) within 24-36 h after thrombolysis; 33 (37%) of these patients were given AP therapy (AP group) and 56 (63%) were not (AP-naïve group). No significant differences were found for the risk of 7-day aggravated ICH (p=0.998), 7-day NIHSS score (p=0.5491), 7-day mortality [odds ratio (OR)=3.427; 95% confidence interval (95% CI)=0.344-34.160; p=0.294], 90-day mortality (OR=0.788, 95% CI=0.154-4.040, p=0.775), or modified Rankin score 5 or 6 at 90-days (OR=1.108, 95% CI=0.249-4.928, p=0.893) between the AP and AP-naïve groups after THEPI.ConclusionsEarly administration of postthrombolytic AP therapy after THEPI does not worsen either the short- or long-term outcome. AP therapy may be a reasonable treatment option for patients with THEPI to reduce the risk of ischemic stroke recurrence.

Acute ischemic stroke and long-term outcome after thrombolysis: nationwide propensity score-matched follow-up study.

Data on long-term outcome after intravenous tissue-type plasminogen activator (tPA) in ischemic stroke are limited. We examined the risk of long-term mortality, recurrent ischemic stroke, and major bleeding, including intracranial and gastrointestinal bleeding, in intravenous tPA-treated patients when compared with intravenous tPA eligible but nontreated patients with ischemic stroke. We conducted a register-based nationwide propensity score-matched follow-up study among patients with ischemic stroke in Denmark (2004-2011). Cox regression analysis was used to compute adjusted hazard ratios for all outcomes. Among 4292 ischemic strokes (2146 intravenous tPA-treated and 2146 propensity score-matched nonintravenous tPA-treated patients), with a follow-up for a median of 1.4 years, treatment with intravenous tPA was associated with a lower risk of long-term mortality (adjusted hazard ratio, 0.66; 95% confidence interval, 0.49-0.88). The long-term risk of recurrent ischemic stroke (adjusted hazard ratio, 1.05; 95% confidence interval, 0.68-1.64) and major bleeding (adjusted hazard ratio, 0.59; 95% confidence interval, 0.24-1.47) did not differ significantly between the intravenous tPA-treated and nontreated patients. Treatment with intravenous tPA in patients with ischemic stroke was associated with improved long-term survival.

Recurrent thromboembolic events after ischemic stroke in patients with cancer.

To determine the cumulative rate and characteristics of recurrent thromboembolic events after acute ischemic stroke in patients with cancer. We retrospectively identified consecutive adult patients with active systemic cancer diagnosed with acute ischemic stroke at a tertiary-care cancer center from 2005 through 2009. Two neurologists independently reviewed all electronic records to ascertain the composite outcome of recurrent ischemic stroke, myocardial infarction, systemic embolism, TIA, or venous thromboembolism. Kaplan-Meier statistics were used to determine cumulative outcome rates. In exploratory analyses, Cox proportional hazard analysis was used to evaluate potential independent associations between a priori selected clinical factors and recurrent thromboembolic events. Among 263 study patients, complete follow-up until death was available in 230 (87%). Most patients had an adenocarcinoma as their underlying cancer (60%) and had systemic metastases (69%). Despite a median survival of 84 days (interquartile range 24-419 days), 90 patients (34%; 95% confidence interval 28%-40%) had 117 recurrent thromboembolic events, consisting of 57 cases of venous thromboembolism, 36 recurrent ischemic strokes, 13 myocardial infarctions, 10 cases of systemic embolism, and one TIA. Kaplan-Meier rates of recurrent thromboembolism were 21%, 31%, and 37% at 1, 3, and 6 months, respectively; cumulative rates of recurrent ischemic stroke were 7%, 13%, and 16%. Adenocarcinoma histology (hazard ratio 1.65, 95% confidence interval 1.02-2.68) was independently associated with recurrent thromboembolism. Patients with acute ischemic stroke in the setting of active cancer (especially adenocarcinoma) face a substantial short-term risk of recurrent ischemic stroke and other types of thromboembolism.

C-Reactive Protein as a Prognostic Marker After Lacunar Stroke

Inflammatory biomarkers predict incident and recurrent cardiac events, but their relationship to stroke prognosis is uncertain. We hypothesized that high-sensitivity C-reactive protein (hsCRP) predicts recurrent ischemic stroke after recent lacunar stroke. Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within Secondary Prevention of Small Subcortical Strokes (SPS3), a phase III trial in patients with recent lacunar stroke. Patients were assigned in factorial design to aspirin versus aspirin plus clopidogrel, and higher versus lower blood pressure targets. Patients had blood samples collected at enrollment and hsCRP measured using nephelometry at a central laboratory. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for recurrence risks before and after adjusting for demographics, comorbidities, and statin use. Among 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), median hsCRP was 2.16 mg/L. There were 83 recurrent ischemic strokes (including 45 lacunes) and 115 major vascular events (stroke, myocardial infarction, and vascular death). Compared with the bottom quartile, those in the top quartile (hsCRP>4.86 mg/L) were at increased risk of recurrent ischemic stroke (unadjusted HR, 2.54; 95% CI, 1.30-4.96), even after adjusting for demographics and risk factors (adjusted HR, 2.32; 95% CI, 1.15-4.68). hsCRP predicted increased risk of major vascular events (top quartile adjusted HR, 2.04; 95% CI, 1.14-3.67). There was no interaction with randomized antiplatelet treatment. Among recent lacunar stroke patients, hsCRP levels predict the risk of recurrent strokes and other vascular events. hsCRP did not predict the response to dual antiplatelets. http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Abstract 67: HsCRP Predicts Recurrent Stroke and Vascular Events among Patients with Lacunar Stroke: The Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) Study

Objective: To determine whether high sensitivity C-reactive protein (hsCRP) predicts recurrent stroke and other vascular events among recent lacunar stroke patients. Background: Inflammatory markers have been associated with risk of first stroke. Their role in predicting recurrence is unclear. Methods: The Levels of Inflammatory Markers in the Treatment of Stroke study is an international prospective study of inflammatory markers among recent lacunar stroke patients enrolled in the NIH-funded randomized Secondary Prevention of Small Subcortical Strokes trial. Patients had blood samples drawn, saved at -80 degrees C, and run at a central lab for hsCRP using nephelometry. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals (HR, 95% CI) for associations of hsCRP with recurrence risk before and after adjusting for demographics, comorbidities, and statin use. Results: Among 1244 lacunar stroke patients (mean 63.3 ± 10.8 years), median hsCRP was 2.16 mg/L (interquartile range 0.93-4.86), and levels differed by age, sex, smoking, and LDL. Median time between stroke and hsCRP measurement was 60 days, and levels were inversely and weakly correlated with proximity to stroke date (r=-0.06, p=0.039). There were 83 recurrent ischemic strokes (45 lacunes), 16 hemorrhages, and 115 major vascular events (stroke, MI, vascular death). Compared to the bottom quartile, those in the top quartile of hsCRP (&gt;4.86 mg/dl) were at increased risk of recurrent ischemic stroke (unadjusted HR 2.54, 95% CI 1.30-4.96), and the risk persisted after adjusting for age, sex, race, region, hypertension, smoking, prior history of stroke, diabetes, lipid levels, and statin use (adjusted HR 2.28, 95% CI 1.14-4.57). HsCRP was associated with an increased risk of major vascular events (top quartile adjusted HR 1.98, 95% CI 1.11-3.54). Results were similar using clinical thresholds of high risk hsCRP (&gt; 3 mg/dl). There was no interaction of randomized antiplatelet treatment with hsCRP levels for stroke risk. Conclusions: Among recent lacunar stroke patients, elevated hsCRP levels predict increased risk of recurrent strokes and other vascular events. Levels of inflammatory markers did not predict a response to dual antiplatelet treatment.

Abstract T P336: Risk of Stroke and Vascular Events and Response to Antiplatelet Therapy in Young Adults with Recent Lacunar Strokes: The SPS3 Study

Background: Incidence of lacunar strokes increases with age. Young stroke adults have better survival rate, but due to longer life expectancy they are at higher risk of stroke recurrence. Objective: The aim of this study was to examine stroke recurrence and major vascular events in young adults with lacunar strokes, and to explore the effectiveness of antiplatelet therapy for secondary stroke prevention among participants in the Secondary Prevention Small Subcortical Stroke trial (SPS3). Methods: The SPS3 study was a double blind, multicenter secondary stroke prevention trial for patients with symptomatic lacunar infarcts. It evaluated the use of antiplatelets (aspirin+clopidrogel vs aspirin) for stroke prevention. Outcomes were ischemic strokes (IS), hemorrhagic strokes (ICH), major vascular events (MVE), and deaths. Univariate analyses were used to compare the frequency rates of these events among young (&lt;50 yrs) and older adults (50+yrs). Interactions between the outcomes and antiplatelet therapy based on age were also examined. Results: Of 3020 patients, 323 (11%) were &lt;50 year old (mean age 46, 67% M). Mean follow-up was 3.4 years. There were no differences on risk of ischemic stroke recurrence or MVE in two groups. The younger group had a 4-fold reduced risk of death (p&lt;0.001) and significantly lower risk of ICH (p=0.03). There was an interaction between age and antiplatelet therapy for all strokes (p=0.02), IS (p=0.04) and MVE (0.01). The young group in the aspirin+clopidogrel arm had lower risk of all strokes (HR=0.51;95%CI:0.25-1.04.p=0.06), of ischemic strokes (HR=0.62;95%CI:0.30-1.27,p=0.2) and of major vascular events (HR=0.45;95%CI:0.23-0.88,p=0.02). Conclusion: In this exploratory analysis, dual antiplatelet therapy with aspirin+clopidogrel significantly reduced the risk of all strokes, major vascular events and deaths among young adults with recent lacunar strokes. The risk of bleeding was not increased. Response to antiplatelet therapy in young adults with stroke may differ from that in older adults, thus our results deserve further investigations.

Pharmacological Secondary Prevention of Ischemic Stroke

The causes of ischemic stroke are widely diverse, ranging from large artery atherosclerosis to cardioembolism, and it is important to use preventive therapy toward the goal reducing the future risk of recurrent ischemic stroke, myocardial infarction, and vascular death. Antithrombotic therapy is one of the fundamental medical approaches for secondary prevention of ischemic stroke, which is broadly divided into two general categories, those that exert their effect via platelet inhibition (antiplatelet agents), and those that influence various factors in the clotting cascade (anticoagulants). In general, the clinical guidelines recommend antiplatelet agents for patients with non-cardioembolic stroke, while anticoagulants is indicated for patients with presumed or proven cardioembolic stroke. Many clinical trials have attempted to test the efficacy and safety of antithrombotics in ischemic stroke. This review will discuss on currently available antithrombotic agents that have demonstrated efficacy for secondary prevention of ischemic stroke. (Brain & NeuroRehabilitation 2014; 7: 76-85)

Transcranial Doppler Ultrasonography CO2 Reactivity Does Not Predict Recurrent Ischaemic Stroke in Patients with Symptomatic Carotid Artery Occlusion

Background: Patients with transient ischaemic attacks (TIAs) or minor disabling ischaemic stroke associated with an internal carotid artery (ICA) occlusion have a high risk of recurrent stroke in case of compromised cerebral blood flow. Recent studies showed that increased oxygen extraction fraction measured by positron emission tomography (PET) is still an independent predictor of subsequent stroke under current medical treatment, but PET facilities are not widely available. Transcranial Doppler (TCD) ultrasonography CO₂ reactivity is a cheap and non-invasive alternative to measure haemodynamic compromise. The aim of our study was to investigate whether TCD CO₂ reactivity is an independent predictor of recurrent ischaemic stroke in a large cohort of patients with symptomatic ICA occlusion in a time where rigorous control of vascular risk factors has been widely implemented in clinical practice. Methods: Between July 1995 and December 2009, we included consecutive patients with TIAs or minor disabling ischaemic stroke (modified Rankin Scale ≤3) associated with ICA occlusion who were referred to the University Medical Centre Utrecht, The Netherlands. All patients were treated with antiplatelet therapy and received rigorous control of vascular risk factors, including statins, treatment for diabetes and hypertension and lifestyle advices. CO₂ reactivity was measured with TCD within 3 months after presentation. We determined the predictive value of TCD CO₂ reactivity for recurrent ischaemic stroke using Cox proportional hazard analysis. Results: We included 201 patients with a median follow-up time of 7.1 years. Mean CO₂ reactivity was 15% (±20 standard deviation). The annual rate for ipsilateral ischaemic stroke was 2.2% [95% confidence interval (CI) 1.4-3.2] and for any recurrent stroke 3.2% (95% CI 2.3-4.4). We did not find a significant relationship between CO₂ reactivity and the risk of ipsilateral [hazard ratio (HR) for every increase in percentage point 1.01, 95% CI 0.99-1.02] or any recurrent ischaemic stroke (HR 1.01, 95% CI 0.998-1.02). Multivariable analysis showed a significant relationship with history of stroke (HR 4.0, 95% CI 1.8-9.0) for ipsilateral recurrent stroke, and age (HR for increase per year 1.05, 95% CI 1.01-1.09) and a history of stroke (HR 3.4, 95% CI 1.7-6.6) for any recurrent stroke. Conclusions: In patients with TIAs or non-disabling stroke associated with occlusion of the carotid artery, the long-term annual risk of stroke is generally low with careful control of vascular risk factors. Impaired CO₂ reactivity measured within 3 months after presentation does not identify the subgroup of patients at high risk of recurrent ischaemic stroke.

Transcatheter closure of patent foramen ovale does not reduce the risk of recurrent ischemic stroke versus medical therapy alone: A meta-analysis of randomized controlled trials

Patent foramen ovale Transcatheter closure Medical therapy Ischemic stroke Randomized controlled trial

Learning curve of Wingspan stenting for intracranial atherosclerosis: single-center experience of 95 consecutive patients

BackgroundSymptomatic brain hemorrhage was a significant cause of periprocedural stroke or death following stenting in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis trial, which...

Cerebral Microbleeds and Recurrent Stroke Risk

To evaluate cerebral microbleeds (CMBs) and future stroke risk (including intracerebral hemorrhage [ICH]) in patients with ischemic stroke (IS) or transient ischemic attack. A systematic review and meta-analysis of prospective cohorts with recent IS/transient ischemic attack. We critically appraised studies and calculated pooled odds ratios (ORs), using the Mantel-Haenszel fixed-effects method, for ICH or recurrent IS, in patients with versus without CMBs. We pooled data from 10 cohorts, including 3067 patients. CMBs were associated with a significant increased risk of any recurrent stroke (OR, 2.25; 95% confidence interval [95% CI], 1.70-2.98; P<0.0001), ICH (OR, 8.52; 95%CI, 4.23-17.18; P=0.007), and IS (OR, 1.55; 95%CI, 1.12-2.13; P<0.0001). When stratified by study population ethnicity (Asian versus Western [mainly white European]), the association of CMBs with ICH was significant for Asian cohorts (5 studies; n=1915; OR, 10.43; 95%CI, 4.59-23.72; P<0.0001) but borderline and of lower magnitude for Western cohorts (4 studies; n=885; OR, 3.87; 95%CI, 0.91-16.4; P=0.066). By contrast, there was a significant association of CMBs with recurrent IS in Western (3 studies; n=899) but not Asian cohorts (4 studies; n=1357; OR, 2.23; 95%CI, 1.29-3.85; P=0.004 compared with OR, 1.30; 95%CI, 0.88-1.93; P=0.192, respectively). There is consistent evidence of an increased risk of recurrent stroke after IS or transient ischemic attack in patients with CMBs. The risk for spontaneous ICH appears to be greater than the risk for recurrent IS. Our findings also suggest that the balance of risk for ICH versus IS differs between Asian and Western cohorts.

Effects of Clopidogrel Added to Aspirin in Patients with Recent Lacunar Stroke

BackgroundLacunar infarcts are a frequent type of stroke caused mainly by cerebral small-vessel disease. The effectiveness of antiplatelet therapy for secondary prevention has not been defined.MethodsWe conducted a double-blind, multicenter trial involving 3020 patients with recent symptomatic lacunar infarcts identified by magnetic resonance imaging. Patients were randomly assigned to receive 75 mg of clopidogrel or placebo daily; patients in both groups received 325 mg of aspirin daily. The primary outcome was any recurrent stroke, including ischemic stroke and intracranial hemorrhage.ResultsThe participants had a mean age of 63 years, and 63% were men. After a mean follow-up of 3.4 years, the risk of recurrent stroke was not significantly reduced with aspirin and clopidogrel (dual antiplatelet therapy) (125 strokes; rate, 2.5% per year) as compared with aspirin alone (138 strokes, 2.7% per year) (hazard ratio, 0.92; 95% confidence interval [CI], 0.72 to 1.16), nor was the risk of recurrent ischemic stroke (hazard ratio, 0.82; 95% CI, 0.63 to 1.09) or disabling or fatal stroke (hazard ratio, 1.06; 95% CI, 0.69 to 1.64). The risk of major hemorrhage was almost doubled with dual antiplatelet therapy (105 hemorrhages, 2.1% per year) as compared with aspirin alone (56, 1.1% per year) (hazard ratio, 1.97; 95% CI, 1.41 to 2.71; P<0.001). Among classifiable recurrent ischemic strokes, 71% (133 of 187) were lacunar strokes. All-cause mortality was increased among patients assigned to receive dual antiplatelet therapy (77 deaths in the group receiving aspirin alone vs. 113 in the group receiving dual antiplatelet therapy) (hazard ratio, 1.52; 95% CI, 1.14 to 2.04; P=0.004); this difference was not accounted for by fatal hemorrhages (9 in the group receiving dual antiplatelet therapy vs. 4 in the group receiving aspirin alone).ConclusionsAmong patients with recent lacunar strokes, the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and did significantly increase the risk of bleeding and death. (Funded by the National Institute of Neurological Disorders and Stroke and others; SPS3 ClinicalTrials.gov number, NCT00059306.)

Ischemic Brain Injury After Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is the second most common cause of stroke and accounts for 8% to 15% of strokes in Western societies with an estimated incidence of 10 to 25 per 100 000 persons.1–3 Despite advances in the field of stroke and neurocritical care,4 the 30-day mortality has not changed significantly over the past 20 years.3 Indeed, ICH has the highest rates of dependence or death among stroke types and proven treatments are lacking. Clinical trials aimed at limiting hemorrhage growth, procoagulant agents for hemostasis,5 and surgical evacuation6 have not translated into improved clinical outcomes. Antihypertensive therapy for the purpose of reducing hematoma growth has been a mainstay of acute management. Guidelines recommend maintaining mean arterial pressure <130 mm Hg during the acute phase7; however, controversies exist given the lack of randomized clinical trial data and uncertainties about the rapidity and target level of blood pressure (BP)-lowering. Recent Phase 2 clinical trials evaluating acute BP control have shown promise in reducing hematoma expansion with an adequate safety profile and Phase 3 trials are underway.8,9 Besides hematoma growth, other pathophysiological processes occur in the setting of ICH and may serve as potential therapeutic targets. In the acute period after ICH, a rapid rise in intracranial pressure (ICP) from an expanding hematoma may reduce cerebral perfusion pressure. In this setting, interventions aimed at BP-lowering and hemostasis may theoretically induce thrombosis or exacerbate brain ischemia, particularly in patients with pre-existing cerebrovascular disease. A recent publication suggests that aggressive BP-lowering may actually cause acute brain ischemia and worsen outcomes after ICH.10 In this review, we outline the data on secondary acute ischemic injury after ICH, review the prevalence of remote ischemic lesions and risk factors associated with their occurrence, explore potential …