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Randomized Controlled Trial
. 2013 Dec 31;8(12):e83759.
doi: 10.1371/journal.pone.0083759. eCollection 2013.

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

Robyn H Guymer  1 , Paul N Baird  1 , Mary Varsamidis  1 , Lucy Busija  2 , Peter N Dimitrov  1 , Khin Zaw Aung  1 , Galina A Makeyeva  1 , Andrea J Richardson  1 , Lyndell Lim  1 , Liubov D Robman  1
Affiliations
Randomized Controlled Trial

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

Robyn H Guymer et al. PLoS One. .

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.

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.

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Conflict of interest statement

Competing Interests: Co-author Paul Baird is a PLOS ONE Editorial Board member. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Flowchart of study participation.
Figure 2
Figure 2. Forest plot of odds ratios (95% confidence intervals) for the effect of simvastatin on AMD progression from different models of the analysis.
See this image and copyright information in PMC

References

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