Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding. (Funded by Bayer and Janssen Research and Development; NAVIGATE ESUS ClinicalTrials.gov number, NCT02313909 .).

In phase 1 of the study, 3 mg/kg daily of cannabidiol (CBD) was given for 30 days to 8 healthy human volunteers. Another 8 volunteers received the same number of identical capsules containing glucose as placebo in a double-blind setting. Neurological and physical examinations, blood and urine analysis, ECG and EEG were performed at weekly intervals. In phase 2 of the study, 15 patients suffering from secondary generalized epilepsy with temporal focus were randomly divided into two groups. Each patient received, in a double-blind procedure, 200-300 mg daily of CBD or placebo. The drugs were administered for as long as 4½ months. Clinical and laboratory examinations, EEG and ECG were performed at 15- or 30-day intervals. Throughout the experiment the patients continued to take the antiepileptic drugs prescribed before the experiment, although these drugs no longer controlled the signs of the disease. All patients and volunteers tolerated CBD very well and no signs of toxicity or serious side effects were detected on examination. 4 of the 8 CBD subjects remained almost free of convulsive crises throughout the experiment and 3 other patients demonstrated partial improvement in their clinical condition. CBD was ineffective in 1 patient. The clinical condition of 7 placebo patients remained unchanged whereas the condition of 1 patient clearly improved. The potential use of CBD as an antiepileptic drug and its possible potentiating effect on other antiepileptic drugs are discussed.

Background:

RESUMO -Foram estudados retrospectivamente 262 pacientes com diagnóstico clínico de acidente vascular cerebral isquêmico (AVCi) permanente, com idade igual ou superior a 60 anos, selecionados dos 1015 registros da Liga de Aterosclerose da Clínica Neurológica da ISCMSP, de 1990ISCMSP, de a 2002. O estudo focalizou as freqüências dos fatores de risco modificáveis para AVCi nesta população idosa, considerando-se sexo e faixa etária dos pacientes. Os resultados evidenciaram que a hipertenção arterial sistêmica é significativamente freqüente (87,8%) entre pacientes idosos com AVCi, independentemente do sexo e da faixa etária. Tabagismo (46,9%) e etilismo (35,1%) revelaram-se fatores de riscos modificáveis freqüentes especialmente entre os homens. As cardiopatias (27,0%), o Diabete Melito (19,9%) e as dislipidemias (15,6%) também se revelaram fatores de risco modificáveis freqüentes em pacientes idosos com AVCi, em ambos os sexos e em ambas as faixas etárias estudadas (60 a 70 anos e mais que 71 anos). Foi relativamente baixa a freqüência de hiperuricemia nesta amostra.PALAVRAS-CHAVE: acidente vascular cerebral isquêmico, idosos, AVC, fatores de risco. Study of the main risk factors frequencies for ischemic cerebrovascular disease in elderly patientsABSTRACT -Two hundred and sixty two patients with clinical diagnosis of permanent ischemic stroke, all of them aged 60 or more were retrospectively studied from the 1015 cerebrovascular diseases (CVD) records of the Atherosclerosis Ligue of the Neurology Clinics of the ISCMSP, from 1990 to 2002. The study emphasized modifiable risk factors frequencies for ischemic stroke in this population, considering gender and age of the patients. Results have evidenced that systemic arterial hypertension is a main risk factor significantly frequent in old people (87.8%), independently of gender and age. Smoking (46.9%) and alcohol consumption (35.1%) have revealed to be very frequent important modifiable risk factors especially among men. Lower frequencies have been presented for cardiac diseases (27.0%), Diabetes Melitus (19.9%), and dislipidemia (15.6%) as risk factors for ischemic stroke in old people of both genders and all ages after 60. There was relatively low frequency of hiperuricemia in this set of patients.KEY WORDS: ischemic stroke, elderly patients, stroke, risk factors.As doenças do aparelho circulatório acarretam taxas de mortalidade proporcional de 32,3%, e constituem as principais causas de óbito no Brasil. Este grupo é liderado pela doença cerebrovascular (DCV), que é responsável por um terço das mortes. 4,5 . O AVC isquêmico (AVCi), ou seja, o déficit neuroló-gico resultante da insuficiência de suprimento sangüíneo cerebral, que pode ser transitório (episódio isquêmico transitório) ou permanente, representa, na população nacional, segundo diferentes estatís-ticas, de 53,0% 6 a 85,0% 6-8 dos casos de AVC, predominando a sua forma permanente. A detecção e o controle dos fatores de risco são tarefas prioritárias, pois permitem redução significativa da inci-

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Background: Embolic strokes of undetermined source comprise up to 20% of ischemic strokes. The stroke recurrence rate is substantial with aspirin, widely used for secondary prevention. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source international trial will compare the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus aspirin for secondary prevention in patients with recent embolic strokes of undetermined source. Main hypothesis: In patients with recent embolic strokes of undetermined source, rivaroxaban 15 mg once daily will reduce the risk of recurrent stroke (both ischemic and hemorrhagic) and systemic embolism (primary efficacy outcome) compared with aspirin 100 mg once daily. Design: Double-blind, randomized trial in patients with embolic strokes of undetermined source, defined as nonlacunar cryptogenic ischemic stroke, enrolled between seven days and six months from the qualifying stroke. The planned sample size of 7000 participants will be recruited from approximately 480 sites in 31 countries between 2014 and 2017 and followed for a mean of about two years until at least 450 primary efficacy outcome events have occurred.

The second part of these Guidelines covers the topics of antiplatelet, anticoagulant, and statin therapy in acute ischemic stroke, reperfusion therapy, and classification of Stroke Centers. Information on the classes and levels of evidence used in this guideline is provided in Part I. A translated version of the Guidelines is available from the Brazilian Stroke Society website (www.sbdcv.com.br).

Background and Purpose— The sources of emboli in patients with embolic stroke of undetermined source (ESUS) are multiple and may not respond uniformly to anticoagulation. In this exploratory subgroup analysis of patients with carotid atherosclerosis in the NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism)-ESUS trial, we assessed whether the treatment effect in this subgroup is consistent with the overall trial population and investigated the association of carotid atherosclerosis with recurrent ischemic stroke. Methods— Carotid atherosclerosis was analyzed either as the presence of mild (ie, 20%–49%) atherosclerotic stenosis or, separately, as the presence of carotid plaque. Primary efficacy outcome was ischemic stroke recurrence. Safety outcomes were major bleeding and symptomatic intracerebral bleeding. Results— Carotid plaque was present in 40% of participants and mild carotid stenosis in 11%. There was no significant difference in ischemic stroke recurrence between rivaroxaban- and aspirin-treated patients among 490 patients with carotid stenosis (5.0 versus 5.9/100 patient-years, respectively, hazard ratio [HR], 0.85; 95% CI, 0.39–1.87; P for interaction of treatment effect with patients without carotid stenosis 0.78) and among 2905 patients with carotid plaques (5.9 versus 4.9/100 patient-years, respectively, HR, 1.20; 95% CI, 0.86–1.68; P for interaction of treatment effect with patients without carotid stenosis 0.2). Among patients with carotid plaque, major bleeding was more frequent in rivaroxaban-treated patients compared with aspirin-treated (2.0 versus 0.5/100 patient-years, HR, 3.75; 95% CI, 1.63–8.65). Patients with carotid stenosis had similar rate of ischemic stroke recurrence compared with those without (5.4 versus 4.9/100 patient-years, respectively, HR, 1.11; 95% CI, 0.73–1.69), but there was a strong trend of higher rate of ischemic stroke recurrence in patients with carotid plaque compared with those without (5.4 versus 4.3/100 patient-years, respectively, HR, 1.23; 95% CI, 0.99–1.54). Conclusions— In ESUS patients with carotid atherosclerosis, we found no difference in efficacy between rivaroxaban and aspirin for prevention of recurrent stroke, but aspirin was safer, consistent with the overall trial results. Carotid plaque was much more often present ipsilateral to the qualifying ischemic stroke than contralateral, supporting an important etiological role of nonstenotic carotid disease in ESUS. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02313909.