More Than 50 Percent Reduction in LDL Cholesterol in Patients With Target LDL <70 mg/dL After a Stroke.

BACKGROUND: Whether a strategy to target an LDL (low-density lipoprotein) cholesterol <70 mg/dL is more effective when LDL is reduced >50% from baseline rather than <50% from baseline has not been investigated. METHODS: The Treat Stroke to Target trial was conducted in France and South Korea in 61 sites between March 2010 and December 2018. Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned to a target LDL cholesterol of <70 mg/dL or 100±10 mg/dL, using statin and/or ezetimibe as needed. We used the results of repeated LDL measurements (median, 5 [2-6] per patient) during 3.9 years (interquartile range, 2.1-6.8) of follow-up. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death. Cox regression model including lipid-lowering therapy as a time-varying variable, after adjustment for randomization strategy, age, sex, index event (stroke or transient ischemic attack), and time since the index event. RESULTS: Among 2860 patients enrolled, patients in the lower target group who had >50% LDL cholesterol reduction from baseline during the trial had a higher baseline LDL cholesterol and a lower LDL cholesterol achieved as compared to patients who had <50% LDL cholesterol reduction (155±32 and 62 mg/dL versus 121±34 and 74 mg/dL, respectively, P<0.001 for both). In the <70 mg/dL target group, patients with >50% LDL reduction had a significant reduction in the primary outcome as compared to the higher target group (hazard ratio, 0.61 [95% CI, 0.43-0.88]; P=0.007) and patients with <50% LDL reduction from baseline had little reduction (hazard ratio, 0.96 [95% CI, 0.73-1.26]; P=0.75). CONCLUSIONS: In this post hoc analysis of the TST trial, targeting an LDL cholesterol of <70 mg/dL reduced the risk of primary outcome compared with 100±10 mg/dL provided LDL cholesterol reduction from baseline was superior to 50%, thereby suggesting that the magnitude of LDL cholesterol reduction was as important to consider as the target level to achieve. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01252875. URL: https://clinicaltrialsregister.eu; Unique identifier: EUDRACT2009-A01280-57.

A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke.

BACKGROUND: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied. METHODS: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes. RESULTS: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups. CONCLUSIONS: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).

Intracranial Hemorrhage in the TST Trial.

BACKGROUND AND PURPOSE: Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH. METHODS: Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL (low-density lipoprotein) cholesterol of <70 mg/dL or 100±10 mg/dL, using statin or ezetimibe. RESULTS: Among 2860 patients enrolled, 31 incident ICH occurred over a median follow-up of 3 years (18 and 13 in the lower and higher target group, 3.21/1000 patient-years [95% CI, 2.38-4.04] and 2.32/1000 patient-years [95% CI, 1.61-3.03], respectively). While there were no baseline predictors of ICH, uncontrolled hypertension (HR, 2.51 [95% CI, 1.01-6.31], P=0.041) and being on anticoagulant (HR, 2.36 [95% CI, 1.00-5.62], P=0.047)] during the trial were significant predictors. On-treatment low LDL cholesterol was not a predictor of ICH. CONCLUSIONS: Targeting an LDL cholesterol of <70 mg/dL compared with 100±10 mg/dL in patients with atherosclerotic ischemic stroke nonsignificantly increased the risk of ICH. Incident ICHs were not associated with low LDL cholesterol. Uncontrolled hypertension and anticoagulant therapy were associated with ICH which has important clinical implications. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.

Yield of Dual Therapy With Statin and Ezetimibe in the Treat Stroke to Target Trial.

BACKGROUND: In atherosclerotic stroke, lipid-lowering treatment with a target LDL (low-density lipoprotein) cholesterol of <70 compared with 100±10 mg/dL reduced the risk of subsequent cardiovascular events. This post hoc analysis explored the relative effects of the combination of statin and ezetimibe (dual therapy) and statin monotherapy in achieving the lower LDL cholesterol target and in reducing the risk of major vascular events, as compared with the higher target group. METHODS: Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned to a target LDL cholesterol of <70 or 100±10 mg/dL, using statin and/or ezetimibe as needed. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death. Cox regression model including lipid-lowering therapy as a time varying variable, after adjustment for randomization strategy, age, sex, index event (stroke or transient ischemic attack), and time since the index event. RESULTS: Among 2860 patients enrolled, patients who were on dual therapy during the trial in the lower target group had a higher baseline LDL cholesterol as compared to patients on statin monotherapy (141±38 versus 131±36, respectively, P<0.001). In patients on dual therapy and on statin monotherapy, the achieved LDL cholesterol was 66.2 and 64.1 mg/dL respectively, and the primary outcome was reduced during dual therapy as compared with the higher target group (HR, 0.60 [95% CI, 0.39-0.91]; P=0.016) but not during statin monotherapy (HR, 0.92 [95% CI, 0.70-1.20]; P=0.52), with no significant increase in intracranial bleeding. CONCLUSIONS: In the TST trial (Treat Stroke to Target), targeting an LDL cholesterol of < 70 mg/dL with a combination of statin and ezetimibe compared with 100±10 mg/dL consistently reduced the risk of subsequent stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01252875. URL: clinicaltrialsregister.eu; Unique identifier: EUDRACT2009-A01280-57.

Evaluation of non-stenotic carotid atherosclerotic plaques with combined FDG-PET imaging and CT angiography in patients with ischemic stroke of unknown origin.

OBJECTIVES: Non-stenotic plaques are an underestimated cause of ischemic stroke. Imaging aspects of high-risk carotid plaques can be identified on CT angiography (CTA) and 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET) imaging. We evaluated in patients with cryptogenic ischemic stroke the usefulness of FDG-PET-CTA. METHODS: 44 patients imaged with CTA and FDG-PET were identified retrospectively. Morphological features were identified on CTA. Intensity of FDG uptake in carotid arteries was quantified on PET. RESULTS: Patients were imaged 7 ± 8 days after stroke. 44 non-stenotic plaques with increased 18F-FDG uptake were identified in the carotid artery ipsilateral to stroke and 7 contralateral. Most-diseased-segment TBR on FDG-PET was higher in artery ipsilateral vs. contralateral to stroke (2.24 ± 0.80 vs. 1.84 ± 0.50; p < .05). In the carotid region with high FDG uptake, prevalence of hypodense plaques and extent of hypodensity on CTA were higher in artery ipsilateral vs. contralateral to stroke (41% vs. 11%; 0.72 ± 1.2 mm2 vs. 0.13 ± 0.43 mm2; p < .05). CONCLUSIONS: In patients with ischemic stroke of unknown origin and non-stenotic plaques, we found an increased prevalence of high-risk plaques features ipsilateral vs. contralateral to stroke on FDG-PET-CTA imaging suggesting a causal role for these plaques.

Carotid Atherosclerosis Evolution When Targeting a Low-Density Lipoprotein Cholesterol Concentration <70 mg/dL After an Ischemic Stroke of Atherosclerotic Origin.

BACKGROUND: The TST trial (Treat Stroke to Target) showed the benefit of targeting a low-density lipoprotein cholesterol (LDL-C) concentration of <70 mg/dL in terms of reducing the risk of major cardiovascular events in 2860 patients with ischemic stroke with atherosclerotic stenosis of cerebral vasculature. The impact on carotid atherosclerosis evolution is not known. METHODS: TST-PLUS (Treat Stroke to Target-Plaque Ultrasound Study) included 201 patients assigned to an LDL-C concentration of <70 mg/dL and 212 patients assigned to a target of 100±10 mg/dL. To achieve these goals, investigators used the statin and dosage of their choice and added ezetimibe as needed. Ultrasonographers were certified and carotid ultrasound examinations were performed using M'Ath software at baseline and at 2, 3, and 5 years. All images were uploaded to the Intelligence in Medical Technologies database directly from the carotid ultrasound device. The central core laboratory performed all offline measurements of the intima-media thickness of both common carotid arteries blinded from the randomization arm. The main outcomes were newly diagnosed atherosclerotic plaque on carotid bifurcation or internal carotid artery using the Mannheim consensus definition and between-group comparison of common carotid arteries intima-media thickness change. RESULTS: After a median follow-up of 3.1 years, the achieved LDL-C concentrations were 64 mg/dL (1.64 mmol/L) in the lower-target group and 106 mg/dL (2.72 mmol/L) in the higher-target group. Compared with the higher-target group, patients in the lower-target group had a similar incidence of newly diagnosed carotid plaque: 46/201 (5-year rate, 26.1%) versus 45/212 (5-year rate, 29.7%). The change in common carotid arteries intima-media thickness was -2.69 µm (95% CI, -6.55 to 1.18) in the higher-target group and -10.53 µm (95% CI, -14.21 to -6.85) in the lower-target group, resulting in an absolute between-group difference of -7.84 µm (95% CI, -13.18 to -2.51; P=0.004). CONCLUSIONS: In patients with ischemic stroke and atherosclerosis, an LDL-C target of <70 mg/dL (1.8 mmol/L) did not reduce the incidence of new carotid plaques but produced significantly greater regression of carotid atherosclerosis than an LDL-C target of 90 to 110 mg/dL. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252875.

Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke.

BACKGROUND: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events. METHODS: We evaluated patients who had had a TIA or minor stroke within 7 days before enrollment in the registry. Among 61 sites that participated in the 1-year outcome study, we selected 42 sites that had follow-up data on more than 50% of their enrolled patients at 5 years. The primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes (whichever occurred first), with an emphasis on events that occurred in the second through fifth years. In calculating the cumulative incidence of the primary outcome and secondary outcomes (except death from any cause), we treated death as a competing risk. RESULTS: A total of 3847 patients were included in the 5-year follow-up study; the median percentage of patients with 5-year follow-up data per center was 92.3% (interquartile range, 83.4 to 97.8). The composite primary outcome occurred in 469 patients (estimated cumulative rate, 12.9%; 95% confidence interval [CI], 11.8 to 14.1), with 235 events (50.1%) occurring in the second through fifth years. At 5 years, strokes had occurred in 345 patients (estimated cumulative rate, 9.5%; 95% CI, 8.5 to 10.5), with 149 of these patients (43.2%) having had a stroke during the second through fifth years. Rates of death from any cause, death from cardiovascular causes, intracranial hemorrhage, and major bleeding were 10.6%, 2.7%, 1.1%, and 1.5%, respectively, at 5 years. In multivariable analyses, ipsilateral large-artery atherosclerosis, cardioembolism, and a baseline ABCD2 score for the risk of stroke (range, 0 to 7, with higher scores indicating greater risk) of 4 or more were each associated with an increased risk of subsequent stroke. CONCLUSIONS: In a follow-up to a 1-year study involving patients who had a TIA or minor stroke, the rate of cardiovascular events including stroke in a selected cohort was 6.4% in the first year and 6.4% in the second through fifth years. (Funded by AstraZeneca and others.).

Vascular origin in acute transient visual disturbance: A prospective study.

BACKGROUND AND PURPOSE: This study was undertaken to validate a clinical score of vascular origin in patients with acute transient visual disturbances (TVDs) without diplopia. METHODS: We conducted a prospective study in an ophthalmology emergency department and a transient ischemic attack (TIA) clinic. Patients underwent clinical evaluation including a tailored questionnaire, brain, vascular, and ophthalmologic investigations, and 3-month follow-up. TVDs were classified according to vascular or nonvascular origin by three independent experts based on all clinical, cerebrovascular, and ophthalmologic investigations, but blind to the questionnaire results. A clinical score was derived based on clinical variables independently associated with a vascular origin, and was externally validated in an independent cohort. RESULTS: An ischemic origin of TVD was found in 45% (67/149) of patients in the derivation cohort. Age and six questions were independently associated with an ischemic origin. A nine-point score (≥70 years old = 2; monocular visual loss = 2; black or white vision = 1; single episode = 1; lack of headache = 2; diffuse, constricted, altitudinal, or lateralized visual loss pattern on drawings = 1) showed good discriminative power in identifying ischemic origin (c-statistic = 0.82) and was replicated in the validation cohort (n = 130, 25% of ischemic origin, c-statistic = 0.75). With a score ≥ 4, sensitivity was 85% (95% confidence interval = 68-95) and specificity was 52% (95% confidence interval = 41-62). In both cohorts, ophthalmologic evaluation found a vascular cause in 4% and was noncontributive in 85%. After 3 months, no patients had a stroke, TIA, or retinal infarct. CONCLUSIONS: Our score may assist in predicting a vascular origin of TVD. Ophthalmologic evaluation, when not readily available, should not delay the neurovascular evaluation.

Oral microbiota and atherothrombotic carotid plaque vulnerability in periodontitis patients. A cross-sectional study.

BACKGROUND: An increased risk of atherothrombotic vascular events has been reported in periodontitis patients. Periodontitis is associated with dysbiotic subgingival biofilms and bacteremia. OBJECTIVE: We hypothesized (a) that the oral microbiome is associated with the carotid microbiome and (b) that periodontitis could contribute to plaque vulnerability. The aim of this study was to determine the associations between periodontitis, the carotid microbiome, and the local innate immune response in carotid atherothrombotic plaques vulnerable to rupture. METHODS: In this cross-sectional study, 45 patients admitted for carotid endarterectomy underwent a preoperative periodontal examination. The volume of intraplaque hemorrhage reflected by the hemoglobin level released in carotid-conditioned media was considered as a criterion of carotid plaque vulnerability. Levels of antibodies against periodontal bacteria were determined in sera. The signature of the oral microbiota was assessed by microbial whole-genome sequencing, nested PCR, and immunostaining in carotid plaque samples. Markers of neutrophil recruitment (leukotriene B4), neutrophil activation (myeloperoxidase, defensins), and cytokines were measured in carotid-conditioned media and/or plasma. RESULTS: All patients exhibited periodontitis. One hundred and forty-four bacterial genera were detected in the carotid microbiome. While Streptococcus was found in 84% of the carotid samples, periodontitis-associated genera were detected in 21%. P. gingivalis DNA and gingipains were also identified in carotid samples. There were significant inverse correlations between periodontal attachment loss/serum anti-P. gingivalis Immunoglobulin A and cytokine inhibiting neutrophils (all P < .01). There were also significant positive correlations between lipopolysaccharides, myeloperoxidase/human neutrophil peptides1-3, and hemoglobin levels (all P < .01). CONCLUSIONS: In patients at risk of stroke, the carotid plaque microbiome was highly diverse and compatible with an oral origin. Periodontitis was significantly associated with neutrophil activation markers and plaque vulnerability to rupture.

Prevalence and Outcome of Potential Candidates for Left Atrial Appendage Closure After Stroke With Atrial Fibrillation: WATCH-AF Registry.

BACKGROUND AND PURPOSE: As a result of contraindications (eg, frailty, cognitive impairment, comorbidities) or patient refusal, many patients with stroke and atrial fibrillation cannot be discharged on oral anticoagulant. Among them, the proportion of potential candidates for left atrial appendage closure (LAAC) and their 12-month outcome is not well known. METHODS: The prospective WATCH-AF registry (Warfarin Aspirin Ten-A Inhibitors and Cerebral Infarction and Hemorrhage and Atrial Fibrillation) enrolled consecutive patients admitted within 72 hours of an acute stroke associated with atrial fibrillation in 2 stroke centers. Scales to evaluate stroke severity, disability, functional independence, risk of fall, cognition, ischemic and hemorrhagic risk-stratification, and comorbidities were systematically collected at admission, discharge, 3, 12 months poststroke. The 2 main end points were death or dependency (modified Rankin Scale score >3) and recurrent stroke (brain infarction and brain hemorrhage). RESULTS: Among 400 enrolled patients (370 with brain infarction, 30 with brain hemorrhage), 31 died before discharge and 57 (14.3%) were possible European Heart Rhythm Association/European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Rhythm Society candidates for LAAC. At 12 months, the rate of death or dependency was 17.9%, and the rate of stroke recurrence was 9.8% in the 274/400 (68.5%) patients discharged on a long-term oral anticoagulant strategy, as compared with 17.5% and 24.7%, respectively, in 57 patients candidate for LAAC. As compared with patients on a long-term oral anticoagulant strategy, there was a 2-fold increase in the risk of stroke recurrence in the group with an indication for LAAC (adjusted hazard ratio, 2.58 [95% CI, 1.40-4.76]; P=0.002). CONCLUSIONS: Fourteen percent of patients with stroke associated with atrial fibrillation were potential candidates for LAAC. The 12-month stroke risk of these candidates was 3-fold the risk of anticoagulated patients.

Ten-year risks of recurrent stroke, disability, dementia and cost in relation to site of primary intracerebral haemorrhage: population-based study.

BACKGROUND: Patients with primary intracerebral haemorrhage (ICH) are at increased long-term risks of recurrent stroke and other comorbidities. However, available estimates come predominantly from hospital-based studies with relatively short follow-up. Moreover, there are also uncertainties about the influence of ICH location on risks of recurrent stroke, disability, dementia and quality of life. METHODS: In a population-based study (Oxford Vascular Study/2002-2018) of patients with a first ICH with follow-up to 10 years, we determined the long-term risks of recurrent stroke, disability, quality of life, dementia and hospital care costs stratified by haematoma location. RESULTS: Of 255 cases with primary ICH (mean/SD age 75.5/13.1), 109 (42.7%) had lobar ICH, 144 (56.5%) non-lobar ICH and 2 (0.8%) had uncertain location. Annual rates of recurrent ICH were higher after lobar versus non-lobar ICH (lobar=4.0%, 2.7-7.2 vs 1.1%, 0.3-2.8; p=0.02). Moreover, cumulative rate of dementia was also higher for lobar versus non-lobar ICH (n/% lobar=20/36.4% vs 16/20.8%, p=0.047), and there was a higher proportion of disability at 5 years in survivors (15/60.0% vs 9/31.0%, p=0.03). The 10-year quality-adjusted life years (QALYs) were also lower after lobar versus non-lobar ICH (2.9 vs 3.8 for non-lobar, p=0.04). Overall, the mean 10-year censor-adjusted costs were £19 292, with over 80% of costs due to inpatient hospital admission costs, which did not vary by haematoma location (p=0.90). CONCLUSION: Compared with non-lobar ICH, the substantially higher 10-year risks of recurrent stroke, dementia and lower QALYs after lobar ICH highlight the need for more effective prevention for this patient group.

An International Report on the Adaptations of Rapid Transient Ischaemic Attack Pathways During the COVID-19 Pandemic.

BACKGROUND: This report aims to describe changes that centres providing transient ischaemic attack (TIA) pathway services have made to stay operational in response to the SARS-CoV-2 pandemic. METHODS: An international cross-sectional description of the adaptions of TIA pathways between 30th March and 6th May 2020. Experience was reported from 18 centres with rapid TIA pathways in seven countries (Australia, France, UK, Canada, USA, New Zealand, Italy, Canada) from three continents. RESULTS: All pathways remained active (n = 18). Sixteen (89%) had TIA clinics. Six of these clinics (38%) continued to provide in-person assessment while the majority (63%) used telehealth exclusively. Of these, three reported PPE use and three did not. Five centres with clinics (31%) had adopted a different vascular imaging strategy. CONCLUSION: The COVID pandemic has led TIA clinics around the world to adapt and move to the use of telemedicine for outpatient clinic review and modified investigation pathways. Despite the pandemic, all have remained operational.

One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke.

BACKGROUND: Previous studies conducted between 1997 and 2003 estimated that the risk of stroke or an acute coronary syndrome was 12 to 20% during the first 3 months after a transient ischemic attack (TIA) or minor stroke. The TIAregistry.org project was designed to describe the contemporary profile, etiologic factors, and outcomes in patients with a TIA or minor ischemic stroke who receive care in health systems that now offer urgent evaluation by stroke specialists. METHODS: We recruited patients who had had a TIA or minor stroke within the previous 7 days. Sites were selected if they had systems dedicated to urgent evaluation of patients with TIA. We estimated the 1-year risk of stroke and of the composite outcome of stroke, an acute coronary syndrome, or death from cardiovascular causes. We also examined the association of the ABCD(2) score for the risk of stroke (range, 0 [lowest risk] to 7 [highest risk]), findings on brain imaging, and cause of TIA or minor stroke with the risk of recurrent stroke over a period of 1 year. RESULTS: From 2009 through 2011, we enrolled 4789 patients at 61 sites in 21 countries. A total of 78.4% of the patients were evaluated by stroke specialists within 24 hours after symptom onset. A total of 33.4% of the patients had an acute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, and 10.4% had atrial fibrillation. The Kaplan-Meier estimate of the 1-year event rate of the composite cardiovascular outcome was 6.2% (95% confidence interval, 5.5 to 7.0). Kaplan-Meier estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. In multivariable analyses, multiple infarctions on brain imaging, large-artery atherosclerosis, and an ABCD(2) score of 6 or 7 were each associated with more than a doubling of the risk of stroke. CONCLUSIONS: We observed a lower risk of cardiovascular events after TIA than previously reported. The ABCD(2) score, findings on brain imaging, and status with respect to large-artery atherosclerosis helped stratify the risk of recurrent stroke within 1 year after a TIA or minor stroke. (Funded by Sanofi and Bristol-Myers Squibb.).

Clinical Significance of Isolated Atypical Transient Symptoms in a Cohort With Transient Ischemic Attack.

BACKGROUND AND PURPOSE: Contrary to typical transient symptoms (TS), atypical TS, such as partial sensory deficit, dysarthria, vertigo/unsteadiness, unusual cortical visual deficit, and diplopia, are not usually classified as symptoms of transient ischemic attack when they occur in isolation, and their clinical relevance is frequently denied. METHODS: Consecutive patients with recent TS admitted in our transient ischemic attack clinic (2003-2008) had systematic brain, arterial, and cardiac investigations. We compared the prevalence of recent infarction on brain imaging, major investigational findings (symptomatic intracranial or extracranial atherosclerotic stenosis ≥50%, cervical arterial dissection, and major source of cardiac embolism), and 1-year risk of major vascular events in patients with isolated typical or atypical TS and nonisolated TS, after exclusion of the main differential diagnoses. RESULTS: Among 1850 patients with possible or definite ischemic diagnoses, 798 (43.1%) had isolated TS: 621 (33.6%) typical and 177 (9.6%) atypical. Acute infarction on brain imaging was similar in patients with isolated atypical and typical TS but less frequent than in patients with nonisolated TS, observed in 10.0%, 11.5%, and 15.3%, respectively (P<0.0001). Major investigational findings were found in 18.1%, 26.4%, and 26.3%, respectively (P=0.06). One-year risk of a major vascular events was not significantly different in the 3 groups. CONCLUSIONS: Transient ischemic attack diagnosis should be considered and investigated in patients with isolated atypical TS.

Symptomatic Patients Remain at Substantial Risk of Arterial Disease Complications Before and After Endarterectomy or Stenting.

BACKGROUND AND PURPOSE: After carotid endarterectomy (CEA) or carotid artery stenting (CAS) in patients with transient ischemic attack or minor ischemic stroke, recurrent stroke risk falls to a low rate on modern medical treatment. METHODS: We used data from 4583 patients with recent transient ischemic attack or minor stroke enrolled in the TIAregistry.org to perform a nested case-control analysis to evaluate pre- and post-CEA/CAS risk. Cases were defined as patients with a CEA/CAS during the 1-year follow-up period. For each case, 2 controls with a follow-up time greater than the time from qualifying event to CEA/CAS were randomly selected, matched by age and sex. Primary outcome was defined as major vascular events (MVE, including stroke, cardiovascular death, and myocardial infarction). RESULTS: The median delay from symptom onset of qualifying event to CEA/CAS was 11 days (interquartile range, 6-23). Overall, patients with CEA/CAS had a higher 1-year risk of MVE than other patients (14.8% versus 5.8%; adjusted hazard ratio, 2.40; 95% confidence interval, 1.61-3.60; P<0.001). During the matched preprocedural period, MVE occurred in 14 (7.5%) cases and in 13 (3.5%) controls, with an adjusted odds ratio =2.46 (95% confidence interval, 1.07-5.64; P=0.03). In the postprocedural period, the risk of MVE was also higher in cases than in controls (adjusted P<0.03). CONCLUSIONS: Patients with CEA/CAS had a higher 12-month risk of MVE, as well as during pre- and postprocedural periods. These results suggest that patients in whom CEA/CAS is anticipated are likely to be an informative population for inclusion in studies testing new antithrombotic strategies started soon after symptom onset.

Differences in Characteristics and Outcomes Between Asian and Non-Asian Patients in the TIAregistry.org.

BACKGROUND AND PURPOSE: This study provides the contemporary causes and prognosis of transient ischemic attack (TIA) and minor stroke in Asians and the direct comparisons with non-Asians. METHODS: The TIAregistry.org enrolled 4789 patients (1149 Asians and 3640 non-Asians) with a TIA or minor ischemic stroke within 7 days of onset. Every participating facility had systems dedicated to urgent intervention of TIA/stroke patients by specialists. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome. RESULTS: Approximately 80% of patients were evaluated within 24 hours of symptom onset. At 1 year, there were no differences in the rates of composite cardiovascular events (6.8% versus 6.0%; P=0.38) and stroke (6.0% versus 4.8%; P=0.11) between Asians and non-Asians. Asians had a lower risk of cerebrovascular disease (stroke or TIA) than non-Asians (adjusted hazard ratio, 0.79; 95% confidence interval, 0.63-0.98; P=0.03); the difference was primarily driven by a lower rate of TIA in Asians (4.2% versus 8.3%; P<0.001). Moderately severe bleeding was more frequent in Asians (0.8% versus 0.3%; P=0.02). In multivariable analysis, multiple acute infarcts (P=0.005) and alcohol consumption (P=0.02) were independent predictors of stroke recurrence in Asians, whereas intracranial stenosis (P<0.001), ABCD2 score (P<0.001), atrial fibrillation (P=0.008), extracranial stenosis (P=0.03), and previous stroke or TIA (P=0.03) were independent predictors in non-Asians. CONCLUSIONS: The short-term stroke risk after a TIA or minor stroke was lower than expected when urgent evidence-based care was delivered, irrespective of race/ethnicity or region. However, the predictors of stroke were different for Asians and non-Asians.

Global Survey of the Frequency of Atrial Fibrillation-Associated Stroke: Embolic Stroke of Undetermined Source Global Registry.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is increasingly recognized as the single most important cause of disabling ischemic stroke in the elderly. We undertook an international survey to characterize the frequency of AF-associated stroke, methods of AF detection, and patient features. METHODS: Consecutive patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19 stroke research centers in 19 different countries. Data were analyzed by global regions and World Bank income levels. RESULTS: Of 2144 patients with ischemic stroke, 590 (28%; 95% confidence interval, 25.6-29.5) had AF-associated stroke, with highest frequencies in North America (35%) and Europe (33%) and lowest in Latin America (17%). Most had a history of AF before stroke (15%) or newly detected AF on electrocardiography (10%); only 2% of patients with ischemic stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The mean age and 30-day mortality rate of patients with AF-associated stroke (75 years; SD, 11.5 years; 10%; 95% confidence interval, 7.6-12.6, respectively) were substantially higher than those of patients without AF (64 years; SD, 15.58 years; 4%; 95% confidence interval, 3.3-5.4; P<0.001 for both comparisons). There was a strong positive correlation between the mean age and the frequency of AF (r=0.76; P=0.0002). CONCLUSIONS: This cross-sectional global sample of patients with recent ischemic stroke shows a substantial frequency of AF-associated stroke throughout the world in proportion to the mean age of the stroke population. Most AF is identified by history or electrocardiography; the yield of conventional short-duration cardiac rhythm monitoring is relatively low. Patients with AF-associated stroke were typically elderly (>75 years old) and more often women.

A history of stroke/transient ischemic attack indicates high risks of cardiovascular event and hemorrhagic stroke in patients with coronary artery disease.

BACKGROUND: Randomized trials of antithrombotics in coronary artery disease have identified previous stroke/transient ischemic attack (TIA) as a marker of increased intracranial bleeding risk. We aimed to further characterize the risk of ischemic and bleeding events associated with a history of stroke/TIA in patients with coronary artery disease. METHODS AND RESULTS: From the international REduction of Atherothrombosis for Continued Health (REACH) registry of atherothrombosis, baseline characteristics and 4-year follow-up of 26,389 patients with coronary artery disease, including 4460 patients (16.9%) with a history of stroke/TIA, were analyzed. Patients with previous stroke/TIA had a higher rate of recurrent cardiovascular events (cardiovascular death, myocardial infarction, or stroke) than patients without (adjusted hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.40-1.65; P<0.001) and specifically of nonfatal ischemic stroke (adjusted HR, 3.06; 95% CI, 2.62-3.57; P<0.001) and nonfatal hemorrhagic stroke rates (adjusted HR, 1.76; 95% CI, 1.00-3.08; P=0.05). Excess risk for nonfatal hemorrhagic stroke appeared confined to the 1st year after a stroke/TIA (adjusted HR, 3.03; 95% CI, 1.51-6.08 for the first year) and was particularly high in patients receiving dual antiplatelet therapy (adjusted HR, 5.21; 95% CI, 1.24-21.90). CONCLUSIONS: In patients with coronary artery disease, a history of stroke/TIA is associated with an independent increase in risk of death, myocardial infarction, or stroke, including both ischemic and hemorrhagic stroke (the latter being smaller in absolute terms). This excess risk of hemorrhagic stroke is particularly high in patients receiving dual antiplatelet therapy and in the 1st year after stroke/TIA. This observation is important for selection of antithrombotic therapy in these patients.

Assessment of smoking care by stroke specialists in patients with recent TIA and minor stroke: an international prospective registry-based cohort study.

OBJECTIVES: The objectives are to assess smoking abstinence and its effects on vascular risk and to report tobacco-cessation counselling and pharmacotherapy use in patients who had a recent minor stroke or transient ischaemic attack (TIA). DESIGN AND SETTING: The TIA registry.org project is a prospective, observational registry of patients with TIA and minor stroke that occurred in the previous 7 days with a 5-year follow-up, involving 61 sites with stroke specialists in 21 countries (Europe, Asia, Latin America and Middle East). Of those, 42 sites had 5-year follow-up data on more than 50% of their patients and were included in the present study. PARTICIPANTS: From June 2009 through December 2011, 3847 patients were eligible for the study (80% of the initial cohort). OUTCOMES: Tobacco counselling and smoking-cessation pharmacotherapy use in smoking patients were reported at discharge. Association between 3-month smoking status and risk of a major cardiovascular event (MACE) was analysed with multivariable Cox regression model. RESULTS: Among 3801 patients included, 835 (22%) were smokers. At discharge, only 35.2% have been advised to quit and 12.5% had smoking-cessation pharmacotherapy prescription. At 3 months, 383/835 (46.9%) baseline smokers were continuers. Living alone and alcohol abuse were associated with persistent smoking; high level of education, aphasia and dyslipidaemia with quitting. The adjusted HRs for MACE at 5 years were 1.13 (95% CI 0.90 to 1.43) in former smokers, 1.31 (95% CI 0.93 to 1.84) in quitters and 1.31 (95% CI 0.94 to 1.83) in continuers. Using time-varying analysis, current smoking at the time of MACE non-significantly increased the risk of MACE (HR 1.31 (95% CI 0.97 to 1.78); p=0.080). CONCLUSION: In the TIAregistry.org, smoking-cessation intervention was used in a minority of patients. Surprisingly, in this population in which, at 5 years, other vascular risk factors were well controlled and antithrombotic treatment maintained, smoking cessation non-significantly decreased the risk of MACE.

Diabetes mellitus, admission glucose, and outcomes after stroke thrombolysis: a registry and systematic review.

BACKGROUND AND PURPOSE: The potential detrimental effect of diabetes mellitus and admission glucose level (AGL) on outcomes after stroke thrombolysis is unclear. We evaluated outcomes of patients treated by intravenous and/or intra-arterial therapy, according to diabetes mellitus and AGL. METHODS: We analyzed data from a patient registry (n=704) and conducted a systematic review of previous observational studies. The primary study outcome was the percentage of patients who achieved a favorable outcome (modified Rankin score ≤2 at 3 months). RESULTS: We identified 54 previous reports that evaluated the effect of diabetes mellitus or AGL on outcomes after thrombolysis. In an unadjusted meta-analysis that included our registry data and previous available observational data, diabetes mellitus was associated with less favorable outcome (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.73-0.79) and more symptomatic intracranial hemorrhage (OR, 1.38; 95% CI, 1.21-1.56). However, in multivariable analysis, diabetes mellitus remained associated with less favorable outcome (OR, 0.77; 95% CI, 0.69-0.87) but not with symptomatic intracranial hemorrhage (OR, 1.11; 95% CI, 0.83-1.48). In unadjusted and in adjusted meta-analysis, higher AGL was associated with less favorable outcome and more symptomatic intracranial hemorrhage; the adjusted OR (95% CI) per 1 mmol/L increase in AGL was 0.92 (0.90-0.94) for favorable outcome, and 1.09 (1.04-1.14) for symptomatic intracranial hemorrhage. CONCLUSIONS: These results confirm that AGL and history of diabetes mellitus are associated with poor clinical outcome after thrombolysis. AGL may be a surrogate marker of brain infarction severity rather than a causal factor. However, randomized controlled evidences are needed to address the significance of a tight glucose control during thrombolysis on clinical outcome.