Cerebral vasospasm is the classic cause of delayed neurological deterioration 
leading to cerebral ischemia and infarction, and thus, poor outcome and 
occasionally death, after aneurysmal subarachnoid hemorrhage (SAH). Advances in 
diagnosis and treatment, principally nimodipine, intensive care management, 
hemodynamic manipulations, and endovascular neuroradiology procedures, have 
improved the prospects for these patients, but outcomes remain disappointing. A 
phase 2b clinical trial (CONSCIOUS-1) demonstrated marked prevention of 
vasospasm with the endothelin antagonist, clazosentan, yet patient outcome was 
not improved. The most likely explanation is that the study was underpowered to 
detect the relatively small improvements in outcome that would be seen with 
prevention of vasospasm, especially when assessed using relatively insensitive 
measures such as the modified Rankin and Glasgow outcome scales. Other possible 
explanations for this result are that adverse effects of treatment affected the 
beneficial effects of the drug. It also is possible that alternative causes of 
neurological deterioration and poor outcome after SAH, including delayed effects 
of acute global cerebral ischemia, thromboembolism, microcirculatory 
dysfunction, and cortical spreading depression, play a role. Clazosentan reduced 
angiographic vasospasm in a dose-dependent manner in patients with aneurysmal 
SAH following coiling or clipping of the aneurysm. Reducing the incidence of 
vasospasm should have an important effect on clinical outcome. A phase 3 
clinical trial (CONSCIOUS-2) will focus on quantifying this outcome in patients 
undergoing aneurysm clipping receiving placebo or 5 mg/h of clazosentan.