Negative interaction of aspirin and streptokinase in acute ischemic stroke: further analysis of the Multicenter Acute Stroke Trial-Italy.

BACKGROUND: Thrombolytic therapy improves the functional outcome in acute ischemic stroke, but the risk of death and cerebral hemorrhage remains high. Aspirin given together with a thrombolytic agent may worsen the risk-to-benefit ratio. We performed a further Multicenter Acute Stroke Trial-Italy (MAST-I) which is the only randomized, controlled trial that has tested the effect of this combination to evaluate the risk of aspirin use plus streptokinase. PATIENTS AND METHODS: We made a post hoc analysis of the MAST-I results comparing streptokinase plus aspirin (156 patients) with streptokinase alone (157 patients). We evaluated the risk of death and cerebral hemorrhage. RESULTS: The combined regimen significantly increased early case fatality from day 3-10 (53 vs. 30; OR 2.1; CI 1.2-3.6). The death excess was solely due to treatments and was not explained by the main prognostic predictors (multifactorial analysis). The cause of death in the combination group was mainly cerebral (42 vs. 24; OR 2.0; CI 1.3-3.7) and associated with hemorrhagic transformation (22 vs. 11; OR 2.2; CI 1.0-5.0). The rate of stroke reoccurrence was not increased in patients treated with streptokinase alone (15 vs. 11; OR 1.4; CI 0.6-3.4). CONCLUSIONS: Stroke patients treated with streptokinase plus aspirin have an increased risk of early death, probably due to cerebral hemorrhagic complications. Whenever thrombolytics are chosen for acute stroke treatment, aspirin and other antiplatelet agents should be avoided.

Hemorrhage after an acute ischemic stroke.MAST-I Collaborative Group.

BACKGROUND AND PURPOSE: Hemorrhagic transformation is frequently seen on CT scans obtained in the subacute phase of ischemic stroke. Its prognostic value is controversial. METHODS: We analyzed 554 patients with acute ischemic stroke enrolled in the Multicenter Acute Stroke Trial-Italy (MAST-I) study in whom a second CT scan was performed on day 5. Presence of 1) intraparenchymal hemorrhages (hematoma or hemorrhagic infarction), 2) extraparenchymal bleeding (intraventricular or subarachnoid) and 3) cerebral edema (shift of midline structure, sulcal effacement or ventricular compression) alone or in association were evaluated. Death or disability at 6 months were considered as "unfavorable outcome." RESULTS: Patients who developed intraparenchymal hemorrhages, extraparenchymal bleeding, or cerebral edema had unfavorable outcome (83%, 100%, and 80%, respectively), but multivariate analysis demonstrated that only extraparenchymal bleeding (collinearity) and cerebral edema (OR=6.8; 95% CI, 4.5 to 10.4) were significant independent prognostic findings. Unfavorable outcome correlated with size of intraparenchymal hemorrhage (chi2 for trend=30.5, P<0.0001). Nevertheless, when a large hematoma was present the negative effect was mostly due to concomitant extraparenchymal bleeding (chi2=51.6, P<0.0001), and when hemorrhagic infarction was detected the negative effect was mostly explained by the association with cerebral edema (chi2=36.6, P<0.0001). CONCLUSIONS: Extraparenchymal bleeding and cerebral edema are the main prognostic CT scan findings in the subacute phase of ischemic stroke. Stroke patients with a high risk for developing these 2 types of brain damage should be identified. Measures to prevent and adequately treat their development should be implemented.

Reliability of hemorrhagic transformation diagnosis in acute ischemic stroke.

BACKGROUND AND PURPOSE: Diagnosis of hemorrhagic transformation (HT) could influence the prognosis and the management of acute ischemic stroke. The interobserver reliability of CT-scan HT classification is evaluated in the present study. METHODS: Fifty 5-day CT scans of patients enrolled in the Multicenter Acute Stroke Trial-Italy (MAST-I) were reviewed independently by two neuroradiologists and one neurologist with CT training. They evaluated the presence and type of intraparenchymal HT (hemorrhagic infarction types I, II, and III and intracerebral hemorrhage) (five-item scale), as well as the presence of intraventricular and/or subarachnoid bleeding according to standardized definitions. RESULTS: Agreement for exclusion of HT and intraventricular/ subarachnoid bleeding was good between the neuroradiologists (kappa = 0.70 and kappa = 0.72) and excellent between the neurologist and each neuroradiologist (kappa = 0.87 and kappa = 0.77, kappa = 0.83, and kappa = 0.81, respectively). The overall agreement for the five-item HT scale between the two neuroradiologists was good (kappa n = 0.65) because of discordance over the last three items. Better overall agreement was obtained with a three-item scale: no hemorrhage, petechial type I hemorrhagic infarction, and other HT (type II and type III hemorrhagic infarction and intracerebral hemorrhage) together (kappa w = 0.82 CONCLUSIONS: Exclusion of HT is a reliable CT diagnosis when made by neuroradiologists and also by a neurologist with CT training. Five- and three-item scales of HT types showed good to excellent reliability. The validity of the scale for predicting short- and long-term outcome should be evaluated in future studies.

Prevalence and outcome of symptomatic carotid lesions in young adults. National Research Council Study Group.

OBJECTIVE: To estimate the prevalence and outcome of symptomatic internal carotid artery lesions in young adults. DESIGN: Multicentre hospital based observational study with five year follow up. SETTING: Seven neurological departments in northern and central Italy. SUBJECTS: 240 patients (115 men) aged 15-44 with a recent transient ischaemic attack or stroke in the carotid territory. MAIN OUTCOME MEASURES: (a) Prevalence of symptomatic internal carotid artery stenosis or occlusion detected by continuous wave Doppler ultrasonography at entry; (b) incidence rates of cerebral, cardiac, and non-vascular death; non-fatal stroke; and non-fatal myocardial infarction. RESULTS: Carotid stenoses of 50-99% and occlusions were found in 38 patients (15.8%). Both conditions were significantly more frequent in patients aged over 35 and in those with hypertension, diabetes mellitus, and stroke at entry. The standardised mortality ratio at five years was 10.5 (95% confidence interval 5.0 to 19.3). Survival of patients with stenoses of 0-49% and occlusions was significantly better than that of patients with stenoses of 50-99%. Carotid stenosis of 50-99% was an independent predictor of death (hazard ratio 7.9; 95% confidence interval 2.2 to 29) and non-fatal stroke (hazard ratio 7.4; 1.5 to 37.4). CONCLUSIONS: The prevalence of carotid stenosis or occlusion in young adults after a cerebrovascular event is low. Though patients with high grade symptomatic carotid stenosis are at risk of non-fetal and fetal events, patients with internal artery occlusion apparently have a benign prognosis.

Pathogenetic and prognostic features of lacunar transient ischaemic attack syndromes.

Lacunar ischaemic stroke syndromes are a well defined subgroup of ischaemic strokes. To determine whether a similar subgroup can be identified among patients with transient ischaemic attacks (TIAs) we studied prospectively 102 consecutive patients within 24 hours of their first TIA. Based on their history they were classified as lacunar TIA syndromes (LTIAS; n = 45) if isolated motor or sensory symptoms or their combination had involved at least two of three body parts (face, arm, leg), whereas all other subjects were grouped as non-lacunar TIA syndromes (NLTIAS; n = 57). All patients were investigated according to a standardised protocol and followed up for an average of 51.1 months. Cardiac and arterial sources of thromboembolism were more frequent among NLTIAS (p = 0.0001). Survival curve analysis demonstrated that LTIAS had a significantly lower long term mortality and incidence of major vascular events. In a multivariate regression analysis, the type of TIA (that is, NLTIAS) was an independent predictor of stroke or death. LTIAS share the same distinct pathogenetic and prognostic features of lacunar ischaemic stroke syndromes. These findings have implications for management of TIAs and for studies of their natural history and treatment.