Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration

Robyn Heather Guymer, Paul N Baird, Mary Varsamidis, Lucy Busija, Peter Dimitrov, Khin Zaw Aung, Galina A Makeyeva, Andrea J Richardson, Lyndell L P Lim, Liubov Robman

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

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. Methodology/Principal Findings: Objectives: 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. Design: A proof of concept double-masked randomized controlled study. Participants: 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. Intervention: Simvastatin 40 mg/day or placebo, allocated 1:1. Main outcome measures: 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. Conclusion/Significance: 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. Trial Registration: Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065
Original languageEnglish
Article numbere83759
Number of pages10
JournalPLoS ONE
Volume8
Issue number12
DOIs
Publication statusPublished - 2013

Cite this