Atorvastatin After Aneurysmal Subarachnoid Hemorrhage
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, have recently been demonstrated to improve endothelial function. Additionally, numerous studies have shown statins as having antiinflammatory and cell-signaling effects together with a selective up-regulation of the eNOS activity. These findings are of potential benefit for the prevention of cerebral vasospasm after a aneurysmal subarachnoid hemorrhage. Indeed, one of the possible mechanisms for this vasospasm is the eNOS depletion or even increase of eNOS expression after the hemorrhage. The purpose of this study is to observe the immediate effect of statins after aneurysmal subarachnoid hemorrhage (aSAH) in cerebral vasospasm and outcome at one year.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Atorvastatin Effect in Incidence and Ischemic Complications of Vasospasm After Subarachnoid Aneurysmal Hemorrhage: a Cohort Study|
- S100B assay measured daily from days 1-15 [ Time Frame: Day 1 through 15 ] [ Designated as safety issue: No ]
- Ischemic lesion volume [ Time Frame: admission upon death or hospital discharge ] [ Designated as safety issue: No ]Ischemic lesion voulume was measured on the last available CT prior to death or hospital discharge
|Study Start Date:||December 2005|
|Study Completion Date:||December 2007|
|Primary Completion Date:||December 2007 (Final data collection date for primary outcome measure)|
Up to now, the preventive and curative treatment of vasospasm secondary to subarachnoid aneurismal hemorrhage has been based on three major approaches: increasing arterial pressure and cerebral blood flow with the use of triple H therapy, increasing the ischemic threshold of neurons with nimodipine and reopening proximal arteries with angioplasty and/or intra-arterial administration of nimodipine, verapamil, milrinone or papaverine. Recently, several teams have observed the efficacy of diverse statins in the prevention of vasospasm by improving the imbalance between the nitric oxide and the endothelin pathways, a major actor in the physiopathology of vasospasm. Indeed, this family of molecules improve the bioavailability of endogenous nitric oxide and upregulate the endothelial NO synthase.
In humans, statin administered within the first 72 hours showed to significantly reduce the incidence of vasospasm up to 50% an therefore, induce a lower morbidity and mortality of this severely ill population. The aim of this study is to demonstrate that atorvastatin reduces the incidence of cerebral vasospasm-related morbidity and mortality within 1 year post aneurysmal subarachnoid hemorrhage (aSAH) treated by either clipping or endovascular coiling.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01569100
|Principal Investigator:||Louis Puybasset, Pr||Departments of Anesthesiology and Critical Care, Pitie-Salpetriere Hospital, APHP, University Pierre et Marie Curie, Paris, France|