title: Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot trial.
abstract: Although statins are being used for secondary prevention of ischemic stroke, recent experimental data have shown new pleiotropic effects of these drugs responsible for their role in neuroprotection. We conducted a pilot, double-blind, randomized, multicenter clinical trial to study for the first time safety and efficacy of simvastatin in the acute phase of ischemic stroke. Simvastatin/placebo was given at 3-12 h from symptom onset to 60 patients with cortical strokes. Efficacy on the evolution of several inflammation markers [interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, C-reactive protein, sApo/Fas, tumor necrosis factor-alpha, E-selectin, L-selectin and nitrites+nitrates] and neurological outcome was evaluated at baseline, day 1, 3, 5, 7 and 90. No differences were found amongst the biomarkers studied regarding treatment allocation. Although simvastatin patients improved significantly by the third day (46.4% vs. 17.9%, P = 0.022), a non-significant increase in mortality and greater proportion of infections (odds ratio 2.4, confidence interval 1.06-5.4) in the simvastatin group were the main safety concerns. Therefore, a larger clinical trial is needed to confirm the net benefit of this therapeutic approach.
authors: Neurovascular Research Laboratory, Neurovascular Unit, Hospital Universitario Vall d'Hebron, Barcelona, Spain. 31862jmv@comb.es
authors: J
authors: J
authors: Montaner
authors: P
authors: P
authors: Chacón
authors: J
authors: J
authors: Krupinski
authors: F
authors: F
authors: Rubio
authors: M
authors: M
authors: Millán
authors: C A
authors: CA
authors: Molina
authors: P
authors: P
authors: Hereu
authors: M
authors: M
authors: Quintana
authors: J
authors: J
authors: Alvarez-Sabín
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D007239:Infections / Q000209:etiology; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects; D020521:Stroke / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D019821:Simvastatin