Abstract
BackgroundHMG 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/SignificanceSimvastatin 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 RegistrationAustralian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065
Highlights
The possible use of HMG Co-A reductase inhibitors, or statins, to slow age-related macular degeneration (AMD) progression, has been considered for some time
Baseline characteristics were similar between the two study groups, except that the number of participants with unilateral advanced AMD was twice as large in the simvastatin group compared to the placebo group (x2 df = 1 = 9.2, p = 0.002)
At 3 years follow-up, the total progression of AMD from baseline was 31/57 (54%) individuals in the simvastatin group and 40/57 (70%) individuals in the placebo group (Table 2). This was mainly explained by the increased number of participants worsening in the severity of non-advanced AMD in the placebo group compared to the simvastatin group (49% vs. 32%, respectively, Table 3)
Summary
The possible use of HMG Co-A reductase inhibitors, or statins, to slow AMD progression, has been considered for some time. HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined
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