title: Total cardiovascular disease burden: comparing intensive with moderate statin therapy insights from the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial.
abstract: OBJECTIVE
  This post-hoc analysis of the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial was designed to assess the comparative treatment efficacy of high-dose atorvastatin and usual-dose simvastatin for the prevention of events subsequent to the first event, using the Wei, Lin, and Weissfeld method.
  
  
  BACKGROUND
  Time-to-first-event analysis of data is frequently utilized to provide efficacy outcome information in coronary heart disease prevention trials. However, during the course of such long-term trials, a large number of events occur subsequent to the first event, the analysis of which will be precluded by this approach.
  
  
  METHODS
  The Wei, Lin, and Weissfeld method allows the analysis of repeated occurrence of events of the same type or of entirely different natures. It regards the recurrence times as multivariate event (failure) times, and models the marginal (individual) distribution for each event with the Cox proportional hazards model.
  
  
  RESULTS
  In the IDEAL trial, compared with patients taking simvastatin 20 to 40 mg daily, patients receiving atorvastatin 80 mg daily had their relative risk of a first cardiovascular event reduced by 17% (p < 0.0001), of a second by 24% (p < 0.0001), of a third by 19% (p = 0.035), of a fourth by 24% (p = 0.058), and of a fifth by 28% (p = 0.117).
  
  
  CONCLUSIONS
  Our results indicate that intensive statin therapy continues to be more effective than standard statin therapy, even beyond the first event, and suggest that clinicians should not hesitate to prescribe high-dose statin therapy for patients experiencing multiple recurrent cardiovascular events.
authors.affiliation: Department of Medicine, Division of Cardiology, Helsinki University Central Hospital, 00290 Helsinki, Finland. matti.j.tikkanen@helsinki.fi
authors.forename: Matti J
authors.initials: MJ
authors.lastname: Tikkanen
authors.forename: Michael
authors.initials: M
authors.lastname: Szarek
authors.forename: Rana
authors.initials: R
authors.lastname: Fayyad
authors.forename: Ingar
authors.initials: I
authors.lastname: Holme
authors.forename: Nilo B
authors.initials: NB
authors.lastname: Cater
authors.forename: Ole
authors.initials: O
authors.lastname: Faergeman
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Anders G
authors.initials: AG
authors.lastname: Olsson
authors.forename: Mogens Lytken
authors.initials: ML
authors.lastname: Larsen
authors.forename: Christina
authors.initials: C
authors.lastname: Lindahl
authors.forename: Terje R
authors.initials: TR
authors.lastname: Pedersen
mesh_terms: D000789:Angina, Unstable / Q000517:prevention & control*; D000069059:Atorvastatin; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D009204:Myocardial Revascularization / Q000706:statistics & numerical data*; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000008:administration & dosage*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin