Xinyi Leng

Early Dual versus Mono Antiplatelet Therapy for Acute Non-Cardioembolic Ischemic Stroke or Transient Ischemic Attack: An Updated Systematic Review and Meta-Analysis

Background— Emerging studies suggest that early administration of dual antiplatelet therapy may be better than monotherapy for prevention of early recurrent stroke and cardiovascular outcomes in acute ischemic stroke and transient ischemic attack (TIA). We performed a meta-analysis of randomized, controlled trials evaluating dual versus mono antiplatelet therapy for acute noncardioembolic ischemic stroke or TIA. Methods and Results— We assessed randomized, controlled trials investigating dual versus mono antiplatelet therapy published up to November 2012 and the CHANCE trial (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events), for efficacy and safety outcomes in adult patients with acute noncardioembolic ischemic stroke or TIA with treatment initiated within 3 days of ictus. In total, 14 studies of 9012 patients were included in the systematic review and meta-analysis. Dual antiplatelet therapy significantly reduced risk of stroke recurrence (risk ratio, 0.69; 95% confidence interval, 0.60–0.80; P<0.001) and the composite outcome of stroke, TIA, acute coronary syndrome, and all death (risk ratio, 0.71; 95% confidence interval, 0.63–0.81; P<0.001) when compared with monotherapy, and nonsignificantly increased risk of major bleeding (risk ratio, 1.35; 95% confidence interval, 0.70–2.59, P=0.37). Analyses restricted to the CHANCE Trial or the 7 double-blind randomized, controlled trials showed similar results. Conclusions— For patients with acute noncardioembolic ischemic stroke or TIA, dual therapy was more effective than monotherapy in reducing risks of early recurrent stroke. The results of the CHANCE study are consistent with previous studies done in other parts of the world.

Evaluating Intracranial Atherosclerosis Rather Than Intracranial Stenosis

Intracranial atherosclerosis (ICAS) is an important cause of ischemic stroke throughout the world, accounting for ≈30% to 50% and 10% of ischemic stroke and transient ischemic attack in Asians and whites, respectively.1 Several imaging modalities, such as transcranial Doppler (TCD), magnetic resonance angiography (MRA), computed tomographic angiography (CTA), and digital subtraction angiography (DSA), are used commonly in routine clinical practice to detect and assess ICAS, as well as in selection criteria of clinical trials.2–4 Although some of these imaging modalities yield flow information, such as TCD revealing velocity data or waveform turbulence and time-of-flight MRA (TOF-MRA) depicting arterial patterns based on blood flow, most attention has been drawn to the maximal percent stenosis of the arterial lumen. The focus on severity of stenosis has been reinforced because severe (70%–99%) atherosclerotic stenosis was demonstrated as an independent predictor for stroke recurrence in the territory of the stenotic artery, with the risk of ≈20% at 1 year, in the Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial.5 However, those patients with a traditionally considered moderate (50%–69%) atherosclerotic stenosis were also at considerable risk of recurrent stroke, ≈10% at 1 year in the WASID study.5,6 In more recent studies, the role of percent stenosis in predicting subsequent stroke risk has been superseded by collateral flow and hemodynamics in the same patient cohort.7,8 Characterization of the atherosclerotic lesion is also represented poorly by percentage of stenosis measured at the narrowest vessel diameter alone. Beyond the maximal luminal stenosis, many other features may reflect the characteristics of ICAS, such as plaque morphology and components, which might also be promising markers in risk stratification of patients with symptomatic ICAS.9 However, from the view of intracranial stenosis, it could also be attributed to causes …

Dual antiplatelet therapy in stroke and ICAS Subgroup analysis of CHANCE

Objective: We aimed to investigate whether the efficacy and safety of clopidogrel plus aspirin vs aspirin alone were consistent between patients with and without intracranial arterial stenosis (ICAS), in the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Methods: We assessed the interaction of the treatment effects of the 2 antiplatelet therapies among patients with and without ICAS, identified by magnetic resonance angiography (MRA) in CHANCE (ClinicalTrials.gov identifier NCT00979589). Results: Overall, 1,089 patients with MRA images available in CHANCE were included in this subanalysis, 608 patients (55.8%) with ICAS and 481 (44.2%) without. Patients with ICAS had higher rates of recurrent stroke (12.5% vs 5.4%; p < 0.0001) at 90 days than those without. But there was no statistically significant treatment by presence of ICAS interaction on either the primary outcome of any stroke (hazard ratio for clopidogrel plus aspirin vs aspirin alone: 0.79 [0.47–1.32] vs 1.12 [0.56–2.25]; interaction p = 0.522) or the safety outcome of any bleeding event (interaction p = 0.277). Conclusions: The results indicated higher rate of recurrent stroke in minor stroke or high-risk TIA patients with ICAS than in those without. However, there was no significant difference in the response to the 2 antiplatelet therapies between patients with and without ICAS in the CHANCE trial. Classification of evidence: This study provides Class II evidence that for patients with acute minor stroke or TIA with and without ICAS identified by MRA, clopidogrel plus aspirin is not significantly different than aspirin alone in preventing recurrent stroke.

Impact of collaterals on the efficacy and safety of endovascular treatment in acute ischaemic stroke: a systematic review and meta-analysis

Objective We aimed to investigate the role of pretreatment collateral status in predicting the efficacy and safety of endovascular treatment (EVT) in acute ischaemic stroke due to cervical and/or cerebral arterial occlusions. Methods Relevant full-text articles published since 1 January 2000, investigating correlations between collateral status and any efficacy or safety outcome in patients undergoing EVT in cohort or case–control studies, or randomised clinical trials, were retrieved by PubMed and manual search. Two authors extracted data from eligible studies and assessed study quality. Risk ratios (RR) were pooled for good versus poor collaterals for outcomes based on a random-effects model. Sensitivity and subgroup analyses were conducted. Results In total, 35 (3542 participants) and 23 (2652 participants) studies were included in qualitative review and quantitative meta-analysis, respectively. Overall, good pretreatment collaterals increased the rate of favourable functional outcome at 3 months (RR=1.98, 95% CI 1.64 to 2.38; p<0.001), and reduced the risks of periprocedural symptomatic intracranial haemorrhage (RR=0.59, 95% CI 0.43 to 0.81; p=0.001) and 3-month mortality (RR=0.49, 95% CI 0.38 to 0.63; p<0.001), as compared with poor collaterals, in patients with acute ischaemic stroke under EVT. No individual study could alter the estimate of overall effect of collateral status, but there were moderate to significant heterogeneities between subgroups of studies with different modes of EVT, different arterial occlusions and different collateral grading methods. Conclusions Good pretreatment collateral status is associated with higher rates of favourable functional outcome, and lower rates of symptomatic intracranial haemorrhage and mortality, in patients with acute ischaemic stroke receiving endovascular therapies.

Impact of Collateral Status on Successful Revascularization in Endovascular Treatment: A Systematic Review and Meta-Analysis.

Background: Pre-treatment collateral status may be associated with the rates of successful revascularization in acute ischemic stroke patients receiving endovascular treatment (EVT). We conducted a systematic review and meta-analysis to synthesize relevant evidence currently available. Methods: Relevant full-text articles published in English since January 1, 2000, reporting associations between collateral status and successful reperfusion and/or recanalization in acute ischemic stroke patients receiving EVT in cohort or case-control studies, or randomized clinical trials, were retrieved through search of PubMed. Study selection, data extraction and study quality assessment were carried out by 2 investigators. Risk ratios (RR) were pooled for good vs. poor collaterals for the outcomes of successful reperfusion and recanalization, based on random-effects models. Subgroup analyses were conducted to explore for potential factors that might interfere with the effects of pre-treatment collateral status on reperfusion by EVT. Results: In total, 27 studies (2,366 subjects) were included in qualitative analysis, among which 24 studies (2,239 subjects) were quantitatively analyzed. Overall, good pre-treatment collaterals significantly increased the rate of both successful reperfusion (RR 1.28, 95% CI 1.17-1.40; p < 0.001) and recanalization (RR 1.23, 95% CI 1.06-1.42; p = 0.006), as compared with poor collaterals. Subgroup analyses revealed that the effects of collateral status on successful reperfusion by EVT might be different between populations with different ethnicities. Conclusions: Good pre-treatment collaterals may enhance the rates of successful reperfusion and recanalization in EVT for acute ischemic stroke. This may partly explain the favorable effects of good pre-treatment collaterals on clinical outcomes of stroke patients receiving EVT. Thus, it would be valuable to assess the collateral status prior to EVT in acute ischemic stroke. But studies are needed to further verify if the positive effects of good collaterals on revascularization by EVT are restricted to certain subgroups of patients.

Computational fluid dynamics modeling of symptomatic intracranial atherosclerosis may predict risk of stroke recurrence.

Background Patients with symptomatic intracranial atherosclerosis (ICAS) of ≥70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset. Methods Patients with a symptomatic ICAS lesion of 70–99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year. Results Overall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (−2.46–0.79), 4.5 (2.2–20.6), and 7.4 (5.2–12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004–1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002–1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594–0.903; P = 0.014) and 0.776 (95% CI, 0.594–0.903; P = 0.002) in receiver operating characteristic analysis. Conclusions Hemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70–99% luminal stenosis.

Magnetic Resonance Angiography Signal Intensity as a Marker of Hemodynamic Impairment in Intracranial Arterial Stenosis

Background Intracranial arterial stenosis (ICAS) is the predominant cause of ischemic stroke and transient ischemic attack in Asia. Change of signal intensities (SI) across an ICAS on magnetic resonance angiography (MRA) may reflect its hemodynamic severity. Methods In-patients with a symptomatic single ICAS detected on 3D time-of-flight MRA were recruited from 2 hospitals. Baseline and 1-year follow-up data were collected. Signal intensity ratio (SIR) [ =  (mean post-stenotic SI -mean background SI)/(mean pre-stenotic SI - mean background SI)] was evaluated on baseline MRA to represent change of SIs across an ICAS. Acute infarct volume was measured on baseline diffusion-weighted images (DWI). Relationships between SIR and baseline characteristics as well as 1y outcomes were evaluated. Results Thirty-six subjects (86.1% males, mean age 55.0) were recruited. Overall, mean SIR was 0.84±0.23. Mean SIRs were not significantly different between the 23 (63.9%) anatomically severe stenoses and the 13 (36.1%) anatomically moderate stenoses (0.80±0.23 versus 0.92±0.21, p = 0.126). SIR was significantly, linearly and negatively correlated to acute infarct volume on DWI (Spearman correlation coefficient −0.471, p = 0.011). Two patients (5.6%) had recurrent ischemic strokes at 1y, not related to SIR values. Conclusions Change of signal intensities across an ICAS on MRA may reflect its hemodynamic and functional severity. Future studies are warranted to further verify the relationships between this index and prognosis of patients with symptomatic ICAS.

Good collateral circulation predicts favorable outcomes in intravenous thrombolysis: a systematic review and meta-analysis

Baseline collateral status has been correlated with outcomes of acute ischaemic stroke patients receiving intravenous thrombolysis (IVT) in previous studies. We carried out the current systematic review and meta‐analysis to synthesize currently available evidence regarding such correlations.

Interobserver Reproducibility of Signal Intensity Ratio on Magnetic Resonance Angiography for Hemodynamic Impact of Intracranial Atherosclerosis

BACKGROUND Changes of signal intensities (SIs) across intracranial atherosclerosis (ICAS) on magnetic resonance angiography (MRA) may reflect hemodynamic impact of the lesion. We evaluated the interobserver reproducibility of an index termed signal intensity ratio (SIR), developed in a previous study to represent the changes of SIs across ICAS on MRA. METHODS Symptomatic ICAS on MRA were retrospectively recruited. Two observers respectively evaluated the images and calculated the SIR as follows, blinded to each others readings: SIR=(mean poststenotic SI-mean background SI)/(mean prestenotic SI-mean background SI). Statistical analyses were performed to evaluate the interobserver reproducibility of this index. RESULTS A total of 102 symptomatic ICASs were enrolled, with 36 (35.3%) lesions of 50%-69% MRA stenoses and others being 70%-99% stenoses or flow void on MRA. Overall, mean SIRs were not significantly different between the 2 observers (.92±.17 versus .93±.17; mean difference -.006±.09; P=.496 for paired t test). Pearson correlation coefficients were >.80 for all analyses, indicating strong linear correlations between SIRs by the 2 observers. Bland-Altman analysis for SIRs of all cases showed no systematic bias between the 2 observers. For different cut-points ranging from .75 to 1.00, the kappa statistics were mostly greater than .6 and interobserver agreements were all greater than 80%, implying substantial agreement between observers. CONCLUSIONS SIR was demonstrated to be highly reproducible between observers in the present study. Future studies are warranted to further explore the role of this index in comprehensive evaluation and risk stratification of symptomatic ICAS.

Signal intensity ratio as a novel measure of hemodynamic significance for intracranial atherosclerosis

Dear Editor Factors affecting hemodynamic significance of symptomatic intracranial arterial stenosis (ICAS), for instance, collateralization, could alter subsequent stroke risk (1), so hemodynamic significance of ICAS may yield a good predictor for stroke risk in patients with symptomatic ICAS. Based on the signal contrast mechanism, flow-related enhancement (2) of time-of-flight (TOF) magnetic resonance angiography (MRA), and hemodynamic features of flowing blood in the case of stenosis, we assumed that changes of signal intensities (SIs) across an arterial stenosis might yield information on its hemodynamic significance. Therefore, in a pilot study, we developed and evaluated a novel index, named SI ratio (SIR), to quantify the hemodynamic significance of ICAS using TOF MRA. The index SIR was calculated as follows: SIR = (mean poststenotic SI – mean background SI)/(mean prestenotic SI – mean background SI), where mean prestenotic, mean poststenotic (Fig. 1a), and left/right background SIs (Fig. 1b) were measured as shown in Fig. 1. SIRs of 26 arteries (18 middle cerebral arteries and eight intracranial internal carotid arteries) selected from patients with 50–99% symptomatic ICAS identified by three-dimensional TOF MRA (3·0 T) were measured and calculated by the same expert twice, and reproducibility of repeated measures was evaluated. Figure 1 MRA maximum intensity projections (MIPs) of an ischemic stroke patient with a short flow void of right MCA. Mean prestenotic and poststenotic SIs were measured using regions of interest (ROI) on the MIP showing the greatest degree of stenosis as follows ... Mean SIRs were both 0·84 for repeated measures, with ranges of 0·35–1·25 and 0·39–1·25, respectively. Mean absolute and relative differences between repeated measures were 0·037 and 5%, respectively. Intrarater agreement was 88% for the 26 arteries studied, and Pearson’s correlation coefficient for repetitive measures was 0·975. Measurement and calculation of the index SIR on TOF MRA were easy to perform and highly reproducible, which makes it feasible to be carried out in clinical practice. Future studies are warranted to further test this novel method for evaluating hemodynamic significance of ICAS and to find out whether it is related to outcomes of patients with symptomatic ICAS.