Percutaneous transluminal angioplasty and stenting for symptomatic intracranial arterial stenosis: a systematic review and meta-analysis

OBJECTIVES: The cumulative safety and efficacy measures of percutaneous transluminal angioplasty and stenting (PTAS) for secondary stroke prevention in patients with symptomatic intracranial arterial stenosis (sICAS) have not previously been evaluated using a meta-analytical approach. METHODS: We conducted a systematic review and random effects meta-analysis of all available randomized controlled trials (RCTs) evaluating the safety and efficacy of PTAS (in comparison with medical therapy) for sICAS. RESULTS: Three RCTs (678 total patients) were included in the quantitative analysis. PTAS was associated with a higher risk of recurrent ischemic stroke in the territory of qualifying artery both within 30 days [risk ratio (RR) = 2.21, 95% confidence interval (CI) 1.10-4.43] and 1 year (RR = 1.92, 95% CI 1.10-3.36). PTAS was also related to a higher risk of any ischemic stroke within 30 days from the index event (RR = 2.08, 95% CI 1.17-3.71). The risk for intracranial hemorrhage was found to be higher in PTAS patients both within 30 days (RR = 10.60, 95% CI 1.98-56.62) and 1 year (RR = 8.15, 95% CI 1.50-44.34). The composite outcome of any stroke or death within 1 year (RR = 2.29, 95% CI 1.13-4.66) and 2 years (RR = 1.52, 95% CI 1.04-2.21) was higher in PTAS than in medical therapy. PTAS was associated with a higher risk of any stroke or death within 2 years in the sICAS subgroup located in posterior circulation (RR = 2.37, 95% CI 1.27-4.42). CONCLUSIONS: PTAS is associated with adverse early and long-term outcomes and should not be recommended in patients with sICAS. Further research to identify subgroups of patients who could also serve as candidates for future interventional trials along with efforts to reduce procedure-related complications are needed

Intravenous thrombolysis for acute ischemic stroke in Greece: the Safe Implementation of Thrombolysis in Stroke registry 15-year experience

Background: Intravenous thrombolysis (IVT) remains the only approved systemic reperfusion treatment for acute ischemic stroke (AIS), however there are scarce data regarding outcomes and complications of IVT in Greece. We evaluated safety and efficacy outcomes of IVT for AIS in Greece using the Safe Implementation of Thrombolysis in Stroke: International Stroke Thrombolysis Register (SITS-ISTR) dataset. Methods: All AIS patients treated with IVT in Greece between December 2002 and July 2017 and recorded in the SITS-ISTR were evaluated. Demographics, risk factors, baseline stroke severity [defined using National Institutes of Health Stroke Scale (NIHSS)], and onset-to-treatment time (OTT) were recorded. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 3-month mortality rates. The efficacy outcomes evaluated a reduction in baseline NIHSS score at 2 and 24 h following IVT onset, 3-month favorable functional outcome [FFO; modified Rankin scale (mRS) scores of 0-1] and 3-month functional independence (FI; mRS-scores of 0-2). The safety and efficacy outcomes were assessed comparatively with previously published data from SITS national and international registries. Results: A total of 523 AIS patients were treated with IVT in 12 Greek centers participating in the SITS-ISTR during the study period (mean age 62.4 ± 12.7; 34.6% women; median baseline NIHSS score: 11 points; median OTT: 150 min). The rates of sICH were 1.4%, 2.3%, and 3.8% according to the SIST-MOST, ECASS II, and NINDS criteria respectively. The median reduction in NIHSS score at 2 and 24 h was 3 [interquartile range (IQR): 1-5] and 5 (IQR: 2-8) points respectively. The 3-month FI, FFO and mortality were 66.5%, 55.6% and 7.9%. All safety and efficacy outcomes were comparable with available data from SITS-ISTR in other European countries. Conclusions: Our study underscores the safety and efficacy of IVT for AIS in Greece. Additional action is necessary in order to increase the availability of IVT in the Greek population and to include more centers in the SITS-ISTR

Hemorrhagic transformation in acute ischemic stroke patients and atrial fibrillation: time to initiation of anticoagulants and outcome

Background: In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results: HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions: In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes

Background: The aim of this study in patients with acute posterior ischemic stroke (PS) and atrial fibrillation (AF) were to evaluate the risks of recurrent ischemic event and severe bleeding and these risks in relation with oral anticoagulant therapy (OAT) and its timing. Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of: stroke recurrence, TIA, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2,470 patients were available for the analysis: 473 (19.1%) with PS and 1,997 (80.9%) AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Conclusions: Patients with posterior or anterior stroke and AF appear to have similar risks of ischemic or hemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT

Anticoagulation After Stroke in Patients With Atrial Fibrillation : To Bridge or Not With Low-Molecular-Weight Heparin?

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.Peer reviewe

Association between non alcoholic steatohepatitis and arterial stiffness in patients with metabolic syndrome before and after hypolipidemic treatment

At present there is no effective treatment for non-alcoholic fatty liver disease (NAFLD) or its advanced form, non-alcoholic steatohepatitis (NASH). The aim of the study was to investigate the effect of rosuvastatin monotherapy on NASH and pulse wave velocity (PWV). This prospective study included 20 biopsy proven patients with NASH, MetS and dyslipidaemia. Patients received lifestyle advice and were treated for 12 months with rosuvastatin (10 mg/day) monotherapy. A repeat biopsy, repeat ultrasonography of the liver and repeat PWV measurements were performed at the end of the study in all patients. Liver enzymes, fasting plasma glucose, serum uric acid , and lipid profile were assessed every 3 months. The primary endpoint was resolution of NASH and improvement in PWV values. The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients in combination with concomitant reduction of PWV values, while the 20th, which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, γ-glutamyltranspeptidase, and alkaline phosphatase activities were normalised by the 6th treatment month. Fasting plasma glucose and glycated haemoglobin were significantly reduced. Lipid values were normalised by the 3rd treatment month. No patient had MetS by the 9th treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group. These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve MetS within 12 months in combination with arterial stiffness improvement. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.Προς το παρόν δεν υπάρχει καμία αποτελεσματική θεραπεία για τη μη αλκοολική λιπώδη νόσο του ήπατος (Non Alcoholic Fatty Liver disease, NAFLD) ή την προχωρημένη μορφή της τη μη αλκοολική στεατοηπατίτιδα (Non Alcoholic Steatohepatitis, NASH), η οποία μπορεί να εξελίχθη σε κίρρωση του ήπατος και τελικά σε ηπάτωμα. Σκοπός της μελέτης ήταν να διερευνηθεί η επίδραση της ροσουβαστατίνης σε ασθενείς με μεταβολικό σύνδρομο (Metabolic Syndrome, MetS) και NASH. Καθώς και η πιθανή συσχέτιση των μεταβολών της NASH με τις μεταβολές της αρτηριακής σκληρίας μετά τη χορήγηση υπολιπιδαιμικής αγωγής. Η προοπτική αυτή μελέτη περιελάμβανε 20 ασθενείς με MetS, δυσλιπιδαιμία και αποδεδειγμένη με βιοψία NASH. Οι ασθενείς έλαβαν συμβουλές τρόπου ζωής και έλαβαν θεραπεία για 12 μήνες με ροσουβαστατίνη (10 mg/ημέρα) ως μονοθεραπεία. Επανάληψη βιοψίας και επανάληψη του υπερηχογραφήματος του ήπατος διεξήχθησαν στο τέλος της μελέτης σε όλους τους ασθενείς. Τα ηπατικά ένζυμα, η γλυκόζη πλάσματος νηστείας, τα επίπεδα του ουρικού οξέος, και το προφίλ των λιπιδίων αξιολογούνταν κάθε 3 μήνες. Το πρωτεύον καταληκτικό σημείο ήταν ο βαθμός υποστροφής της μη αλκοολικής στεατοηπατίτιδας σε συνδυασμό με την ελάττωση των τιμών της ταχύτητας του σφυγμικού κύματος (Pulse Wave Velocity, PWV). Η επαναληπτική βιοψία ήπατος και το επαναληπτικό υπερηχογράφημα έδειξε πλήρη υποστροφής της NASH σε 19 ασθενείς καθώς και σημαντική βελτίωση των τιμών της PWV σε διαδοχικές ανά εξάμηνο μετρήσεις. Ο 20ος ασθενής, ο οποίος δεν είχε καμία βελτίωση, αλλά ούτε επιδείνωση, εμφάνισε αρτηριακή υπέρταση και αύξηση των επιπέδων των τριγλυκεριδίων κατά τη διάρκεια της μελέτης, κατά πάσα πιθανότητα λόγω των αλλαγών στον τρόπο ζωής, συμπεριλαμβανομένης και της κατάχρησης αλκοόλ. Οι δραστηριότητες των ηπατικών ενζύμων του ορού αλανινική αμινοτρανσφεράση, ασπαρτική αμινοτρανσφεράση, γάμμα-γλουταμυλοτρανσπεπτιδάση και αλκαλική φωσφατάση ομαλοποιήθηκαν από τον 6ο μήνα της θεραπείας. Η γλυκόζη νηστείας του πλάσματος και η τιμή της γλυκοζυλιωμένης αιμοσφαιρίνης μειώθηκαν στατιστικά. Οι τιμές των λιπιδίων ομαλοποιήθηκαν από τον 3ο μήνα της θεραπείας. Κανένας ασθενής δεν είχε MetS από τον 9ο μήνα της θεραπείας. Ο δείκτης μάζας σώματος και η περίμετρος της μέσης παρέμειναν αμετάβλητες κατά τη διάρκεια της μελέτης. Έτσι, οι μεταβολές στην ηπατική παθολογία και λειτουργία θα πρέπει να αποδοθούν αποκλειστικά στη μονοθεραπεία με ροσουβαστατίνη. Τα ευρήματα αυτά υποδηλώνουν ότι η μονοθεραπεία με ροσουβαστατίνη θα μπορούσε να βελτιώσει την αποδεδειγμένη με βιοψία στεατοηπατίτιδα με παράλληλη ευνοϊκή επίδραση της αρτηριακής σκληρίας και να προκαλέσει σημαντική βελτίωση των παραμέτρων του MetS εντός 12 μηνών. Αυτές οι επιδράσεις αλλά και η μείωση της γλυκόζης νηστείας του πλάσματος και των επιπέδων ουρικού οξέος στον ορό μπορεί να μειώσουν σημαντικά τον κίνδυνο της σχετιζόμενης με το καρδιαγγειακό σύστημα, αλλά και με το ήπαρ, νοσηρότητας και θνησιμότητας σε ασθενείς με μη αλκοολική στεατοηπατίτιδα. Αυτά τα ευρήματα χρειάζονται επιβεβαίωση από μεγαλύτερες μελέτες

Potential Utility of Neurosonology in Paroxysmal Atrial Fibrillation Detection in Patients with Cryptogenic Stroke

Background: Occult paroxysmal atrial fibrillation (PAF) is a common and potential treatable cause of cryptogenic stroke (CS). We sought to prospectively identify independent predictors of atrial fibrillation (AF) detection in patients with CS and sinus rhythm on baseline electrocardiogram (ECG), without prior AF history. We had hypothesized that cardiac arrhythmia detection during neurosonology examinations (Carotid Duplex (CDU) and Transcranial Doppler (TCD)) may be associated with higher likelihood of AF detection. Methods: Consecutive CS patients were prospectively evaluated over a six-year period. Demographics, clinical and imaging characteristics of cerebral ischemia were documented. The presence of arrhythmia during spectral waveform analysis of CDU/TCD was recorded. Left atrial enlargement was documented during echocardiography using standard definitions. The outcome event of interest included PAF detection on outpatient 24-h Holter ECG recordings. Statistical analyses were performed using univariate and multivariate logistic regression models. Results: A total of 373 patients with CS were evaluated (mean age 60 ± 11 years, 67% men, median NIHSS-score 4 points). The rate of PAF detection of any duration on Holter ECG recordings was 11% (95% CI 8%–14%). The following three variables were independently associated with the likelihood of AF detection on 24-h Holter-ECG recordings in both multivariate analyses adjusting for potential confounders: age (OR per 10-year increase: 1.68; 95% CI: 1.19–2.37; p = 0.003), moderate or severe left atrial enlargement (OR: 4.81; 95% CI: 1.77–13.03; p = 0.002) and arrhythmia detection during neurosonology evaluations (OR: 3.09; 95% CI: 1.47–6.48; p = 0.003). Conclusion: Our findings underline the potential utility of neurosonology in improving the detection rate of PAF in patients with CS