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.).

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.

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.

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.

Overlap of diseases underlying ischemic stroke: the ASCOD phenotyping.

BACKGROUND AND PURPOSE: ASCOD phenotyping (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; and D, dissection) assigns a degree of likelihood to every potential cause (1 for potentially causal, 2 for causality is uncertain, 3 for unlikely causal but disease is present, 0 for absence of disease, and 9 for insufficient workup to rule out the disease) commonly encountered in ischemic stroke. We used ASCOD to investigate the overlap of underlying vascular diseases and their prognostic implication. METHODS: A single rater applied ASCOD in 405 patients enrolled in the Asymptomatic Myocardial Ischemia in Stroke and Atherosclerotic Disease study. RESULTS: A was present in 90% of patients (A1=43% and A2=15%), C in 52% (C1=23% and C2=14%), and S in 66% (S1=11% and S2=2%). On the basis of grades 1 and 2, 25% of patients had multiple underlying diseases, and 80% when all 3 grades were considered. The main overlap was found between A and C; among C1 patients, A was present in 92% of cases (A1=28%, A2=20%, and A3=44%). Conversely, among A1 patients, C was present in 47% of cases (C1=15%, C2=15%, and C3=17%). Grades for C were associated with gradual increase in the 3-year risk of vascular events, whereas risks were similar across A grades, meaning that the mere presence of atherosclerotic disease qualifies for high risk, regardless the degree of likelihood for A. CONCLUSIONS: ASCOD phenotyping shows that the large overlap among the 3 main diseases, and the high prevalence of any form of atherosclerotic disease, reinforces the need to systematically control atherosclerotic risk factors in all ischemic strokes.

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.

Spectrum of transient visual symptoms in a transient ischemic attack cohort.

BACKGROUND AND PURPOSE: Transient visual symptoms (TVS) are common complaints. They can be related to transient ischemic attacks, but the nature of the symptoms often remains uncertain, and data on prognosis are scarce. We studied the prevalence, presentation, and effect of different types of TVS, paying particular attention to the association with high-risk pathology of embolism. METHODS: A total of 2398 patients with suspected transient ischemic attack admitted to the SOS-TIA clinic between January 2003 and December 2008 underwent immediate evaluation and treatment. RESULTS: Eight hundred twenty-six (34.5%) patients had TVS, including 422 (17.6%) patients with isolated TVS. Transient monocular blindness was the most frequent TVS (36.3%), followed by diplopia (13.4%), homonymous lateral hemianopia (12.3%), bilateral positive visual phenomena (10.8%), and lone bilateral blindness (4.5%). Positive diffusion-weighted imaging was found in 11.8%, 8.1%, 8.1%, and 5.0% of patients with homonymous lateral hemianopia, diplopia, lone bilateral blindness, and transient monocular blindness, respectively. Among 1850 patients (595 patients with TVS) with definite/possible transient ischemic attack or minor stroke, a major source of embolism of cardiac or arterial origin was found less frequently in patients with isolated or nonisolated TVS than in patients without TVS (19.6%; 19.7% versus 28.1%, respectively; P<0.001). However, we found a higher rate of atrial fibrillation in patients with homonymous lateral hemianopia (23.2%) than in patients with other TVS (4.0%; adjusted odds ratio, 6.71; 95% confidence interval, 2.99-15.06) or nonvisual symptoms (9.1%; adjusted odds ratio, 4.39; 95% confidence interval, 2.26-8.50). CONCLUSIONS: Approximately 20% of patients with TVS had a major source of embolism detected, requiring urgent management. Atrial fibrillation was particularly frequent in patients with transient homonymous lateral hemianopia.

Coronary artery disease and risk of major vascular events after cerebral infarction.

BACKGROUND AND PURPOSE: The impact of asymptomatic coronary artery disease on the risk of major vascular events in patients with cerebral infarction is unknown. METHODS: Four hundred five patients with acute cerebral infarction underwent carotid, femoral artery, thoracic, and abdominal aorta ultrasound examination. Of 342 patients with no known coronary heart disease, 315 underwent coronary angiography. We evaluated the 2-year risk of major vascular events (myocardial infarction, resuscitation after cardiac arrest, hospitalization for unstable angina or heart failure, stroke, or major peripheral arterial disease events) in patients with known coronary heart disease (n=63), and in the no known coronary heart disease group (n=315) as a function of coronary angiographic status (n=315). RESULTS: At 2 years, the estimated risk of major vascular events was 11.0% (95% confidence interval, 8.2-14.7). According to baseline coronary angiography, estimated risk was 3.4% in patients with no coronary artery disease (n=120), 8.0% with asymptomatic coronary artery stenosis <50% (n=113), 16.2% with asymptomatic coronary artery stenosis ≥ 50% (n=81), and 24.1% with known coronary heart disease (P<0.0001). Using no coronary artery disease as the reference, the age- and sex-adjusted hazard ratio (95% confidence interval) of vascular events was 2.10 (0.63-6.96) for asymptomatic coronary stenosis <50%, 4.36 (1.35-14.12) for asymptomatic coronary stenosis ≥ 50%, and 6.86 (2.15-21.31) for known coronary artery disease. CONCLUSIONS: In patients with nonfatal cerebral infarction, presence and extent of asymptomatic stenoses on coronary angiography are strong predictors of major vascular events within 2 years.

Is intracerebral hemorrhage a time-dependent phenomenon after successful combined intravenous and intra-arterial therapy?

BACKGROUND AND PURPOSE: Onset-to-reperfusion time (ORT) has recently emerged as an essential prognostic factor in acute ischemic stroke therapy. Although favorable outcome is associated with reduced ORT, it remains unclear whether intracranial bleeding depends on ORT. We therefore sought to determine whether ORT influenced the risk and volume of intracerebral hemorrhage (ICH) after combined intravenous and intra-arterial therapy. METHODS: Based on our prospective registry, we included 157 consecutive acute ischemic stroke patients successfully recanalized with combined intravenous and intra-arterial therapy between April 2007 and October 2011. Primary outcome was any ICH within 24 hours posttreatment. Secondary outcomes included occurrence of symptomatic ICH (sICH) and ICH volume measured with the ABC/2. RESULTS: Any ICH occurred in 26% of the study sample (n=33). sICH occurred in 5.5% (n=7). Median ICH volume was 0.8 mL. ORT was increased in patients with ICH (median=260 minutes; interquartile range=230-306) compared with patients without ICH (median=226 minutes; interquartile range=200-281; P=0.008). In the setting of sICH, ORT reached a median of 300 minutes (interquartile range=276-401; P=0.004). The difference remained significant after adjustment for potential confounding factors (adjusted P=0.045 for ICH; adjusted P=0.002 for sICH). There was no correlation between ICH volume and ORT (r=0.16; P=0.33). CONCLUSIONS: ORT influences the rate but not the volume of ICH and appears to be a critical predictor of symptomatic hemorrhage after successful combined intravenous and intra-arterial therapy. To minimize the risk of bleeding, revascularization should be achieved within 4.5 hours of stroke onset.

Dramatic recovery in acute ischemic stroke is associated with arterial recanalization grade and speed.

BACKGROUND AND PURPOSE: Dramatic recovery (DR) is a predictor of stroke outcome among others. However, after successful recanalization, systematic favorable outcome is not the rule. We sought to analyze the impact of recanalization on DR in patients with acute ischemic stroke eligible for any revascularization strategies (either intravenous or endovascular). METHODS: We analyzed data collected between April 2007 and May 2011 in our prospective clinical registry. All patients with acute ischemic stroke with National Institutes of Health Stroke Scale≥10 at admission and an identification of arterial status before treatment were included. DR was defined as National Institutes of Health Stroke Scale≤3 at 24 hours or a decrease of ≥10 points within 24 hours. RESULTS: DR occurred in 75 of 255 patients with acute ischemic stroke (29.4%). Patients with persistent occlusion had a low DR rate (11.1%) than those with no documented occlusion (36.5%) and those with occlusion followed by recanalization (35.3%; both P<0.001). Among patients with recanalization monitored by angiography, DR was higher among patients with complete recanalization than among those with partial recanalization (46.8% versus 14.3%; P<0.001) and increased with tertiles of time to recanalization (Ptrend=0.002). In multivariable logistic regression analysis, grade and time to recanalization appeared independently associated with DR; the adjusted ORs were 4.17 (95% CI, 1.61-10.77) for complete recanalization and 1.24 (95% CI, 1.04-1.48) for each 30-minute time decrease. Patients with versus without DR more frequently had modified Rankin Scale≤1 (67.6% versus 9.0%; P<0.001) and less frequently had hemorrhage (17.3% versus 33.9%; P=0.024). CONCLUSIONS: DR is strongly associated with favorable clinical outcome and is dependent on complete recanalization and time to recanalization.

Atherogenic dyslipidemia in patients with transient ischemic attack.

BACKGROUND AND PURPOSE: There is mounting evidence that atherogenic dyslipidemia (ie, low high-density lipoprotein cholesterol combined with high triglyceride concentrations) is an independent predictor of high cardiovascular risk and possibly of stroke. METHODS: All patients included in the SOS-TIA cohort underwent an initial standardized evaluation, including medical history, physical examination, routine blood biochemistry, and diagnostic testing, and were followed for 1 year. Lipid profile was evaluated under fasting conditions. Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol blood concentration ≤ 40 mg/dL and triglycerides ≥ 150 mg/dL. RESULTS: Among 1471 consecutive patients with transient ischemic attack (TIA) or minor stroke, overall prevalence of atherogenic dyslipidemia was 5.8%, but varied from 4.6% to 11.1%, depending on final diagnosis (possible TIA or TIA with a cerebral ischemic lesion, respectively). Prevalence of atherogenic dyslipidemia was independently associated with male sex, diabetes, and body mass index, but not with ABCD2 score. Atherogenic dyslipidemia also strongly associated with symptomatic intracranial stenosis ≥ 50% (adjusted odds ratio, 2.77; 95% CI, 1.38-5.55), but not with symptomatic extracranial stenosis ≥ 50% (adjusted odds ratio, 1.20; 95% CI, 0.64-2.26). Despite appropriate secondary prevention treatment, 90-day stroke risk was greater in patients with versus without atherogenic dyslipidemia (4.8% versus 1.7%; P=0.04). CONCLUSIONS: The atherogenic dyslipidemia phenotype in patients with TIA may be associated with intracranial artery stenosis and higher risk of early recurrent stroke. Additional data are needed to confirm these findings and to assess the best way to reduce important residual risk in such patients.

Outcomes of mechanical endovascular therapy for acute ischemic stroke: a clinical registry study and systematic review.

BACKGROUND AND PURPOSE: Recanalization is a powerful predictor of stroke outcome in patients with arterial occlusion. Intravenous recombinant tissue plasminogen activator is limited by its recanalization rate, which may be improved with mechanical endovascular therapy (MET). However, the benefit and safety of MET remain to be determined. The aim of this study was to give reliable estimates of efficacy and safety outcomes of MET. METHODS: We analyzed data from our prospective clinical registry and conducted a systematic review of all previous studies using MET published between January 1966 and November 2009. RESULTS: From April 2007 to November 2009, 47 patients with acute stroke were treated with MET at Bichat Hospital. The literature search identified 31 previous studies involving a total of 1066 subjects. In the meta-analysis, including our registry data, the overall recanalization rate was 79% (95% CI, 73-84). Meta-analysis of clinical outcomes showed a pooled estimate of 40% (95% CI, 34-46; 27 studies) for favorable outcome, 28% (95% CI, 23-33; 28 studies) for mortality, and 8% (95% CI, 6-10; 27 studies) for symptomatic intracranial hemorrhage. The likelihood of a favorable outcome increased with the use of thrombolysis (OR, 1.99; 95% CI, 1.23-3.22) and with proportion of patients with isolated middle cerebral artery occlusion (OR per 10% increase, 1.14; 95% CI, 1.04-1.25). CONCLUSIONS: MET is associated with acceptable safety and efficacy in stroke patients, and it may be a therapeutic option in those presenting with isolated middle cerebral artery occlusion.

Prevalence of coronary atherosclerosis in patients with cerebral infarction.

BACKGROUND AND PURPOSE: there is an overlap between stroke and coronary heart disease, but the exact prevalence of coronary artery disease in patients with nonfatal cerebral infarction is unclear, particularly when there is no known history of coronary heart disease. METHODS: we consecutively enrolled 405 patients presenting with acute cerebral infarction documented by neuroimaging who underwent carotid and femoral artery, thoracic, and abdominal aorta ultrasound examinations. Of the 342 patients with no known coronary heart disease, 315 underwent coronary angiography a median of 8 days (interquartile range, 6-11) after stroke onset. RESULTS: coronary plaques on angiography, regardless of stenosis severity, were present in 61.9% of patients (95% confidence interval [CI], 56.5-67.3) and coronary stenoses ≥ 50% were found in 25.7% (95% CI, 20.9-30.5). The overall prevalence of coronary plaque increased with the number of arterial territories (carotid or femoral arteries) involved, with an adjusted odds ratio of coronary artery disease of 1.25 (95% CI, 0.58-2.71) for presence of plaque in 1 territory, and 4.31 (95% CI, 1.92-9.68) for presence of plaque in both territories, compared with no plaque in either territory. The presence of plaque in both femoral and carotid arteries had an age- and sex-adjusted positive predictive value of 84% for presence of coronary plaque and a negative predictive value of 44%. CONCLUSIONS: there is a high burden of silent coronary artery disease in patients with nonfatal cerebral infarction and no known coronary heart disease, even in the absence of systemic atherosclerosis. The prevalence is even higher in patients with evidence of carotid and/or femoral plaque.

Yield of systematic transcranial Doppler in patients with transient ischemic attack.

OBJECTIVE: Urgent evaluation and treatment of transient ischemic attack (TIA) patients in a dedicated TIA clinic may reduce the 90-day stroke risk by 80%. ABCD2 (Age, Blood pressure, Clinical features, Duration, Diabetes) score and magnetic resonance imaging abnormalities help to identify patients at high risk of stroke. Our aim was to determine whether the use of transcranial Doppler (TCD) examination on arrival at the TIA clinic yields additional information that facilitates the identification of patients at high risk of stroke recurrence. METHODS: Between January 2003 and December 2007, 1,881 patients were admitted to SOS-TIA clinic (a TIA clinic with around-the-clock access). Clinical and vascular assessment included TCD performed by a neurologist immediately after admission. Stroke prevention measures were initiated on arrival, in accordance with guidelines. All patients were followed for 1 year after presentation to the SOS-TIA clinic. RESULTS: A total of 1,823 TCD examinations were performed within 4 hours of admission. Intracranial narrowing or occlusion was found in 8.8% of patients, and was independently associated with age, hypertension, and diabetes. After 1-year follow-up on best preventive therapy, the incidence of recurrent vascular events (intracranial revascularization for TIA recurrence, stroke, myocardial infarction, and vascular death combined) was 7.0% in patients with intracranial narrowing or occlusion and 2.4% in those without (log-rank, p = 0.007). The hazard ratio of combined outcome for the presence of intracranial narrowing or occlusion was 2.29 (95% confidence interval [CI], 1.15-4.56; p = 0.02) in multivariate analysis including age, gender, hypertension, and diabetes, and was 2.50 (95%CI, 1.24-5.05; p = 0.01) in multivariate analysis including ABCD2 score > or =4. INTERPRETATION: Immediate TCD examination on arrival at the TIA clinic is feasible and could help to identify patients at high risk of vascular events recurrence. This study supports a systematic intracranial vascular examination in the initial management of TIA.

Impact of a combined intravenous/intra-arterial approach in octogenarians.

BACKGROUND: Intravenous (IV) alteplase is not currently recommended in octogenarian patients, and the benefit/risk ratio of endovascular (intra-arterial, IA) therapy remains to be determined. The aim of this study was to determine the impact of a combined IV-IA approach in octogenarians. METHODS: From a single-centre interventional study, we report age-specific outcomes of patients treated by a combined IV-IA thrombolytic approach. Patients ≥80 years with documented arterial occlusion treated by conventional IV thrombolysis constituted the control group. RESULTS: Among 84 patients treated by the IV-IA approach, those ≥80 years (n = 25) had a similar rate of early neurological improvement to that of patients <80 years, whereas the 90-day favourable outcome rate was lower in octogenarians (adjusted odds ratio, OR, 0.21; 95% confidence interval, CI, 0.06-0.75). No difference in symptomatic intracranial haemorrhage was observed whereas a higher rate of 90-day mortality (adjusted OR, 3.27; 95% CI, 0.76-14.14) and asymptomatic intracranial haemorrhage (adjusted OR, 6.39; 95% CI, 1.54-26.63) were found in patients ≥80 years old. Among octogenarians, and compared to IV-thrombolysis-treated patients (n = 24), patients treated by the IV-IA approach had a higher rate of recanalization (76 vs. 33%, p = 0.003) associated with increased early neurological improvement (32 vs. 8%, p = 0.07). Although there was a higher rate of asymptomatic intracranial haemorrhage (44 vs. 8%, p = 0.005) observed in the IV-IA group, no difference existed in symptomatic intracranial haemorrhage rates and 90-day favourable outcome. CONCLUSION: The IV-IA approach in octogenarians was associated with lower efficacy at 3 months and higher mortality and asymptomatic haemorrhagic complications than in patients <80 years old. Definite recommendations cannot be given, but an endovascular approach may cause more harm than positive effects in patients over 80 years and should not be considered outside an approved protocol.

Outcomes of intravenous recombinant tissue plasminogen activator therapy according to gender: a clinical registry study and systematic review.

BACKGROUND AND PURPOSE: The natural history of stroke is worse in women than in men. Controversial data have been published on the efficacy of thrombolysis with recombinant tissue plasminogen activator (rtPA) according to gender. We evaluated gender differences in the efficacy and safety outcomes of intravenous rtPA using a clinical registry and systematic review. METHODS: Since January 2002, we collected baseline characteristics and efficacy and safety outcomes for patients who received intravenous rtPA in our center. We performed a systematic PubMed literature search for previous observational studies that examined gender effects on outcomes after intravenous rtPA treatment. RESULTS: No gender difference in good outcome at 3 months (adjusted OR for women, 1.41; 95% CI, 0.76 to 2.60) and in 90-day mortality (adjusted OR, 1.38; 95% CI, 0.59 to 3.19) was found in our registry. We identified 16 studies that evaluated the gender effect among intravenous rtPA-treated patients. None of these studies supported a gender difference in favorable outcome, and one suggested an increased risk of mortality in men. In unadjusted partial meta-analysis in 4074 women and 5840 men including our registry data, we found a trend toward a lower risk of symptomatic intracranial hemorrhage in women (crude OR, 0.87; 95% CI, 0.68 to 1.10). CONCLUSIONS: These results suggest no gender difference in outcome among patients treated with intravenous rtPA.

Does ABCD2 score below 4 allow more time to evaluate patients with a transient ischemic attack?

BACKGROUND AND PURPOSE: The National Institute for Clinical Excellence (NICE) recommends that patients with a transient ischemic attack and ABCD(2) score > or =4 and those with >2 transient ischemic attacks within 1 week be admitted for urgent complete etiologic evaluation within 24 hours and that those with an ABCD(2) score <4 be evaluated less urgently within 1 week. METHODS: Using data from 1176 patients with a definite or possible transient ischemic attack or minor stroke included in the SOS-TIA registry (January 2003 to June 2007), we studied the usefulness of the conventional ABCD(2) score cutoff as well as the NICE criteria for urgent admission to a stroke unit defined as presence of symptomatic internal carotid artery stenosis > or =50%, symptomatic intracranial artery stenosis > or =50%, or major cardiac source of embolism. RESULTS: Among 697 patients with an ABCD(2) score <4, 20% required immediate consideration for emergency treatment (eg, symptomatic internal carotid stenosis > or =50% in 9.1% of patients, symptomatic intracranial stenosis in 5.0%, atrial fibrillation in 5.9%, other major cardiac source of embolism in 2.1%) in comparison to 31.6% of 497 patients with an ABCD(2) score > or =4. The sensitivity and specificity of ABCD(2) score > or =4 or NICE criteria for discriminating between patients requiring admission or not were <62% with low positive predictive values (<30%) and high negative predictive values (> or =80%). CONCLUSIONS: One in 5 patients with an ABCD(2) score <4 had high-risk disease requiring urgent treatment decision-making. When triaging on an ABCD(2) score, we recommend adding systematic carotid ultrasound (or a default angiographic CT scan) and electrocardiography within 24 hours before postponing complete transient ischemic attack evaluation.

Comparison of intravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and confirmed arterial occlusion (RECANALISE study): a prospective cohort study.

BACKGROUND: The efficacy of intravenous (IV) alteplase is restricted by the speed of recanalisation and the site of the occlusion. The aim of this study was to ascertain the effect of a combined IV-endovascular approach (intra-arterial alteplase and, if required, additional thrombectomy) in patients with stroke due to arterial occlusion. METHODS: We compared recanalisation rates, neurological improvement at 24 h, and functional outcome at 3 months between two periods (February, 2002, to March, 2007, vs April, 2007, to October, 2008) in patients in a prospective registry who were treated with different regimens of alteplase within 3 h of symptom onset. Patients with confirmed occlusion who were treated before April, 2007, were treated with IV alteplase; after April, 2007, patients were treated with a systematic IV-endovascular approach. Analysis was by intention to treat. FINDINGS: 46 (87%) of 53 patients treated with the IV-endovascular approach achieved recanalisation versus 56 (52%) of 107 patients in the IV group (adjusted relative risk [RR] 1.49, 95% CI 1.21-1.84; p=0.0002). Early neurological improvement (NIHSS score of 0 or 1 or an improvement of 4 points or more at 24 h) occurred in 32 (60%) patients in the IV-endovascular group and 42 (39%) patients in the IV group (adjusted RR 1.36, 0.97-1.91; p=0.07). Favourable outcome (mRS of 0-2 at 90 days) occurred in 30 (57%) patients in the IV-endovascular group and 47 (44%) patients in the IV group (adjusted RR 1.16, 0.85-1.58; p=0.35). The mortality rate at 90 days was 17% in both groups, and symptomatic intracranial haemorrhage was reported in five (9%) patients in the IV-endovascular group and in 12 (11%) patients in the IV group. Better clinical outcome was associated with recanalisation in both groups and with time to recanalisation in the IV-endovascular group. INTERPRETATION: An IV-endovascular approach is associated with higher recanalisation rates than is IV alteplase in patients with stroke and confirmed arterial occlusion. In patients treated with an IV-endovascular approach, a shorter time from symptom onset to recanalisation is associated with better clinical outcomes.

Twelve-month outcome in patients with stroke and atrial fibrillation not suitable to oral anticoagulant strategy: the WATCH-AF registry.

Aims: Long-term oral anticoagulant (LTOAC) reduces ischaemic stroke recurrences. Because of bleeding history, frailty, cognitive impairment, comorbidities or patient refusal, many cannot be discharged from stroke unit on LTOAC. Proportion and outcome of these patients is not well known. Methods: The Warfarin Aspirin Ten-a inhibitor Cerebral infarction and Haemorrhage and atrial fibrillation (AF) prospective registry enrolled consecutive patients with an acute stroke associated with AF. Scales to evaluate stroke severity, disability, functional independence, cognition, risk of fall, ischaemic and haemorrhagic risk stratification were systematically collected at admission, discharge, 3 and 12 months poststroke. The two main 12-month endpoints were death or dependency (modified Rankin Scale >3) and recurrent stroke. Results: Among 400 patients (370 brain infarctions, 30 brain haemorrhages), 274 were discharged on LTOAC, 31 died before discharge and 95 (24%) were not discharge on anticoagulant (frailty, bedridden or demented, EHRA/ESC contraindication to anticoagulant). Death or dependency and recurrent stroke occurred in 19.8% and 9.9%, respectively, in patient on anticoagulant, and 33.5% and 27.2% in those not on anticoagulant (both p<0.001). Patient not anticoagulated at discharge had a 1.6-fold increase in the risk of death or dependency at 12 months (HR 1.65; 95% CI 1.05 to 2.61; p=0.032) and a 2.5-fold increase in the risk of stroke (HR 2.46; 95% CI 1.36 to 4.44; p=0.003). Conclusions: One-fourth of patients with stroke associated with AF are not discharged on anticoagulation and have a dramatic increase in the risk of death or dependency at 12 months as well as recurrent stroke. Alternative treatments should be trialled in these patients.