Summary Background Clazosentan, an endothelin receptor antagonist, significantly and dose-dependently reduced angiographic vasospasm after aneurysmal subarachnoid haemorrhage (aSAH). We investigated ...whether clazosentan reduced vasospasm-related morbidity and all-cause mortality. Methods In this randomised, double-blind, placebo-controlled, phase 3 study, we randomly assigned patients with aSAH secured by surgical clipping to clazosentan (5 mg/h, n=768) or placebo (n=389) for up to 14 days (27 countries, 102 sites, inpatient and outpatient settings) using an interactive web response system. The primary composite endpoint (week 6) included all-cause mortality, vasospasm-related new cerebral infarcts, delayed ischaemic neurological deficit due to vasospasm, and rescue therapy for vasospasm. The main secondary endpoint was dichotomised extended Glasgow outcome scale (GOSE; week 12). This trial is registered with ClinicalTrials.gov , number NCT00558311. Findings In the all-treated dataset, the primary endpoint was met in 161 (21%) of 764 clazosentan-treated patients and 97 (25%) of 383 placebo-treated patients (relative risk reduction 17%, 95% CI −4 to 33; p=0·10). Poor functional outcome (GOSE score ≤4) occurred in 224 (29%) clazosentan-treated patients and 95 (25%) placebo-treated patients (−18%, −45 to 4; p=0·10). Lung complications, anaemia, and hypotension were more common with clazosentan. Mortality (week 12) was 6% in both groups. Interpretation Clazosentan at 5 mg/h had no significant effect on mortality and vasospasm-related morbidity or functional outcome. Further investigation of patients undergoing endovascular coiling of ruptured aneurysms is needed to fully understand the potential usefulness of clazosentan in patients with aSAH. Funding Actelion Pharmaceuticals.
The safety and efficacy of bypass surgery to achieve cerebral revascularization for cerebral hypoperfusion are controversial. However, bypass surgery still plays an important role for a select group ...of patients. The indication to perform a high-flow or low-flow bypass in cases of acute symptomatic artery occlusion is not defined. Neurologic symptoms in acute symptomatic occlusion are usually blood pressure dependent, and acute blood flow restoration may be considered. This report reviews the case of a patient with an acute carotid occlusion in which a two-stage bypass technique was used to achieve revascularization and discusses the issues influencing the decision-making.
Abstract Background The purpose of this study was to examine a possible association between standard meteorological variables and their changes and the occurrence and clinical features of SAH. ...Methods Univariate association between the clinical/radiographic variables of patients with SAH and standard meteorological variables was evaluated. Next, a multivariate analysis was performed to find independent meteorological predictors for the occurrence of SAH by using a binary logistic regression analysis. Results Univariate analysis showed significant differences between bleeding days and non-bleeding days for the number of change days (maximal atmospheric difference of the day >10 hPa) ( P < .001); for the maximal relative humidity ( P < .05); for the maximal difference of vapor pressure of the day 24 hours before the bleeding day ( P < .006) and between cluster days and noncluster days for the number of change days ( P < .001); for the maximal difference of temperature of the day ( P < .035); and for the maximal, minimal, and mean relative humidity ( P < .027, P < .018, and P < .03, respectively). In the multivariate models, the variable “change day” (OR, 3.7; 95% CI, 1.2-11.3) and direction of the atmospheric pressure difference of the day (OR, 2.6; 95% CI, 1.8-7.8) were retained as independent predictors for the occurrence of SAH. For the variable cluster day as dependent variable, only change day was maintained in the model (OR, 6.9; 95% CI, 4.7-10.8). Conclusions Atmospheric pressure changes of more than 10 hPa within 24 hours are an independent predictor of clustering of patients with SAH. Hypertension is an independent risk factor for the occurrence of SAH at change day.
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