title: Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration.
abstract: BACKGROUND
  HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined.
  
  
  RESULTS
  
  
  
  OBJECTIVE
  To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes.
  
  
  METHODS
  A proof of concept double-masked randomized controlled study.
  
  
  METHODS
  114 participants aged 53 to 91 years, with either bilateral intermediate AMD or unilateral non-advanced AMD (with advanced AMD in fellow eye), BCVA ≥ 20/60 in at least one eye, and a normal lipid profile.
  
  
  METHODS
  Simvastatin 40 mg/day or placebo, allocated 1:1.
  
  
  METHODS
  Progression of AMD either to advanced AMD or in severity of non-advanced AMD. Results. The cumulative AMD progression rates were 70% in the placebo and 54% in the simvastatin group. Intent to treat multivariable logistic regression analysis, adjusted for age, sex, smoking and baseline AMD severity, showed a significant 2-fold decrease in the risk of progression in the simvastatin group: OR 0.43 (0.18-0.99), p = 0.047. Post-hoc analysis stratified by baseline AMD severity showed no benefit from treatment in those who had advanced AMD in the fellow eye before enrolment: OR 0.97 (0.27-3.52), p = 0.96, after adjusting for age, sex and smoking. However, there was a significant reduction in the risk of progression in the bilateral intermediate AMD group compared to placebo [adjusted OR 0.23 (0.07-0.75), p = 0.015]. The most prominent effect was observed amongst those who had the CC (Y402H) at risk genotype of the CFH gene [OR 0.08 (0.02-0.45), p = 0.004]. No evidence of harm from simvastatin intervention was detected.
  
  
  CONCLUSIONS
  Simvastatin may slow progression of non-advanced AMD, especially for those with the at risk CFH genotype CC (Y402H). Further exploration of the potential use of statins for AMD, with emphasis on genetic subgroups, is warranted.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065.
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Guymer
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Varsamidis
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia ; Biostatistics Unit, Faculty of Health, Deakin University, Burwood, Victoria, Australia.
authors.forename: Lucy
authors.initials: L
authors.lastname: Busija
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Dimitrov
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Khin Zaw
authors.initials: KZ
authors.lastname: Aung
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Galina A
authors.initials: GA
authors.lastname: Makeyeva
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Richardson
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Lyndell
authors.initials: L
authors.lastname: Lim
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Liubov D
authors.initials: LD
authors.lastname: Robman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053329:Apolipoprotein E2 / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008268:Macular Degeneration / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011379:Prognosis; D012307:Risk Factors; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D053329:Apolipoprotein E2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017242:Complement Factor H; D019821:Simvastatin