title: Effects of intense low-density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack: the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.
abstract: OBJECTIVE
  The intention-to-treat analysis of data from the placebo-controlled Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial found 80 mg atorvastatin per day reduced the risk of stroke and major coronary events in patients with recent stroke or transient ischemic attack. This benefit was present despite only a 78% net difference in adherence to randomized treatment over the course of the trial. In this exploratory analysis, our aim was to evaluate the benefit and risks associated with achieving a >or=50% low-density lipoprotein cholesterol (LDL-C) reduction from baseline.
  
  
  METHODS
  This post hoc analysis was based on 55,045 LDL-C measurements among the 4731 patients enrolled in SPARCL (average, 11.6 measurements per patient) during a mean follow-up of 4.9 years. At each postrandomization LDL-C assessment, percent change in LDL-C from baseline for each patient was classified as no change or increase from baseline (32.7% of measurements), <50% LDL-C reduction (39.4%), or >or=50% reduction (27.9%).
  
  
  RESULTS
  Compared with no change or an increase in LDL-C, analysis of time-varying LDL-C change showed that patients with >or=50% LDL-C reduction had a 31% reduction in stroke risk (hazard ratio, 0.69, 95% CI, 0.55 to 0.87, P=0.0016), a 33% reduction in ischemic stroke (P=0.0018), no statistically significant increase in hemorrhagic stroke (P=0.8864), and a 37% reduction in major coronary events (P=0.0323). There was no increase in the incidence of myalgia or rhabdomyolysis. Persistent liver enzyme elevations were more frequent in the group with >or=50% LDL-C reduction.
  
  
  CONCLUSIONS
  As compared with having no change or an increase in LDL-C, achieving a >or=50% lowering was associated with a greater reduction in the risk of stroke and major coronary events with no increase in brain hemorrhages.
authors.affiliation: Department of Neurology and Stroke Centre, Bichat University Hospital, Denis Diderot University and Medical School, 46, rue Henri Huchard, 75018, Paris, France. amarenco@ccr.jussieu.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Amarenco
authors.forename: Larry B
authors.initials: LB
authors.lastname: Goldstein
authors.forename: Michael
authors.initials: M
authors.lastname: Szarek
authors.forename: Henrik
authors.initials: H
authors.lastname: Sillesen
authors.forename: Amy E
authors.initials: AE
authors.lastname: Rudolph
authors.forename: Alfred
authors.initials: A
authors.lastname: Callahan
authors.forename: Michael
authors.initials: M
authors.lastname: Hennerici
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: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D008078:Cholesterol, LDL / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002546:Ischemic Attack, Transient / Q000097:blood* / Q000517:prevention & control*; D008055:Lipids / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D012306:Risk; D020521:Stroke / Q000097:blood* / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D008055:Lipids