title: Results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial by stroke subtypes.
abstract: OBJECTIVE
  The SPARCL trial showed that atorvastatin 80 mg/d reduces the risk of stroke and other cardiovascular events in patients with recent stroke or transient ischemic attack (TIA). We tested the hypothesis that the benefit of treatment varies according to index event stroke subtype.
  
  
  METHODS
  Subjects with stroke or TIA without known coronary heart disease were randomized to atorvastatin 80 mg/d or placebo. The SPARCL primary end point was fatal or nonfatal stroke. Secondary end points included major cardiovascular events (MCVE; stroke plus major coronary events). Cox regression models testing for an interaction with treatment assignment were used to explore potential differences in efficacy based on stroke subtype.
  
  
  RESULTS
  For subjects randomized to atorvastatin versus placebo, a primary end point occurred in 13.1% versus 18.6% of those classified as having large vessel disease (LVD, 15.8% of 4,731 participants), in 13.1% versus 15.5% of those with small vessel disease (SVD, 29.8%), in 11.2% versus 12.7% of those with ischemic stroke of unknown cause (21.5%), in 7.6% versus 8.8% of those with TIA (30.9%), and in 22.2% versus 8.3% of those with hemorrhagic stroke (HS, 2%) at baseline. There was no difference in the efficacy of treatment for either the primary end point (LVD hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.49 to 1.02, TIA HR 0.81, CI 0.57 to 1.17, SVD HR 0.85, CI 0.64 to 1.12, unknown cause HR 0.87, CI 0.61 to 1.24, HS HR 3.24, CI 1.01 to 10.4; P for heterogeneity=0.421), or MCVEs (P for heterogeneity=0.360) based on subtype of the index event. As compared to subjects with LVD strokes, those with SVD had similar MCVE rates (19.2% versus 18.5% over the course of the trial), and similar overall reductions in stroke and MCVEs.
  
  
  CONCLUSIONS
  Atorvastatin 80 mg/d is similarly efficacious in preventing strokes and other cardiovascular events, irrespective of baseline ischemic stroke subtype.
authors.affiliation: INSERM U-698 and Denis Diderot University, Paris, France. pierre.amarenco@bch.aphp.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Amarenco
authors.forename: Oscar
authors.initials: O
authors.lastname: Benavente
authors.forename: Larry B
authors.initials: LB
authors.lastname: Goldstein
authors.forename: Alfred
authors.initials: A
authors.lastname: Callahan
authors.forename: Henrik
authors.initials: H
authors.lastname: Sillesen
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hennerici
authors.forename: Steve
authors.initials: S
authors.lastname: Gilbert
authors.forename: Amy E
authors.initials: AE
authors.lastname: Rudolph
authors.forename: Lisa
authors.initials: L
authors.lastname: Simunovic
authors.forename: Justin A
authors.initials: JA
authors.lastname: Zivin
authors.forename: K Michael A
authors.initials: KM
authors.lastname: Welch
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000069059:Atorvastatin; D002545:Brain Ischemia / Q000453:epidemiology / Q000517:prevention & control*; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000008:administration & dosage*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D010919:Placebos; D011758:Pyrroles; D000069059:Atorvastatin