title: High-dose atorvastatin is superior to moderate-dose simvastatin in preventing peripheral arterial disease.
abstract: OBJECTIVE
  To study whether high-dose versus usual-dose statin treatment reduces the incidence of peripheral artery disease (PAD) and what is the effect of high-dose statin treatment on cardiovascular disease (CVD) outcome in patients with PAD.
  
  
  RESULTS
  In the Incremental Decrease in End Points Through Aggressive Lipid Lowering trial, 8888 post-myocardial infarction patients were randomised to high-dose or usual-dose statin therapy (atorvastatin 80 mg/day vs simvastatin 20-40 mg/day). We investigated the effect of high-dose versus usual-dose statins on the pre-specified outcome PAD incidence, and additionally performed a posthoc analysis of the efficacy of high-dose statins in reducing CVD risk among patients with PAD. During a median follow-up of 4.8 years, 94 patients (2.2%) receiving atorvastatin and 135 patients (3.2%) receiving simvastatin developed PAD (HR=0.70, 95% CI 0.53 to 0.91; p=0.007). The risk of major coronary events was almost twofold higher in patients with PAD at baseline, but was no longer significant after adjusting for the adverse cardiovascular risk profile. In PAD patients, major coronary events occurred in fewer patients in the atorvastatin group (14.4%) than in the simvastatin group (20.1%), but the difference did not reach statistical significance. (HR=0.68, 95% CI 0.41 to 1.11; p=0.13). Atorvastatin treatment significantly reduced overall cardiovascular (p=0.046) and coronary events (p=0.004), and coronary revascularisation (p=0.007) in these patients.
  
  
  CONCLUSIONS
  High-dose statin therapy with atorvastatin significantly reduced the incidence of PAD compared with usual-dose statin therapy with simvastatin. Patients with a history of PAD at baseline were at higher risk of future coronary events and this risk was reduced by high-dose atorvastatin treatment.
  
  
  BACKGROUND
  NCT00159835 (URL: http://clinicaltrials.gov/show/NCT00159835).
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Stoekenbroek
authors.affiliation: Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: S Matthijs
authors.initials: SM
authors.lastname: Boekholdt
authors.affiliation: Pfizer Inc., New York, New York, USA.
authors.forename: Rana
authors.initials: R
authors.lastname: Fayyad
authors.affiliation: Pfizer Inc., New York, New York, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Laskey
authors.affiliation: Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki and the Folkhälsan Research Center, Helsinki, Finland.
authors.forename: Matti J
authors.initials: MJ
authors.lastname: Tikkanen
authors.affiliation: University of Oslo and Centre of Preventive Medicine, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Terje R
authors.initials: TR
authors.lastname: Pedersen
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D009204:Myocardial Revascularization / Q000706:statistics & numerical data; D009426:Netherlands / Q000453:epidemiology; D058729:Peripheral Arterial Disease / Q000453:epidemiology / Q000517:prevention & control*; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage*; D012537:Scandinavian and Nordic Countries / Q000453:epidemiology; D019821:Simvastatin / Q000008:administration & dosage*
chemical_list: D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin