Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration.
<h4>Background</h4>HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined.<h4>Methodology/principal findings</h4><h4>Objectives</h4>To evaluate the effect of simvast...
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oai:doaj.org-article:af9016b6ce98442ab17214514f70a60a2021-11-18T08:39:31ZProof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration.1932-620310.1371/journal.pone.0083759https://doaj.org/article/af9016b6ce98442ab17214514f70a60a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24391822/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined.<h4>Methodology/principal findings</h4><h4>Objectives</h4>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.<h4>Design</h4>A proof of concept double-masked randomized controlled study.<h4>Participants</h4>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.<h4>Intervention</h4>Simvastatin 40 mg/day or placebo, allocated 1:1.<h4>Main outcome measures</h4>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.<h4>Conclusion/significance</h4>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.<h4>Trial registration</h4>Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065.Robyn H GuymerPaul N BairdMary VarsamidisLucy BusijaPeter N DimitrovKhin Zaw AungGalina A MakeyevaAndrea J RichardsonLyndell LimLiubov D RobmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e83759 (2013) |
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Medicine R Science Q Robyn H Guymer Paul N Baird Mary Varsamidis Lucy Busija Peter N Dimitrov Khin Zaw Aung Galina A Makeyeva Andrea J Richardson Lyndell Lim Liubov D Robman Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration. |
| description |
<h4>Background</h4>HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined.<h4>Methodology/principal findings</h4><h4>Objectives</h4>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.<h4>Design</h4>A proof of concept double-masked randomized controlled study.<h4>Participants</h4>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.<h4>Intervention</h4>Simvastatin 40 mg/day or placebo, allocated 1:1.<h4>Main outcome measures</h4>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.<h4>Conclusion/significance</h4>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.<h4>Trial registration</h4>Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065. |
| format |
article |
| author |
Robyn H Guymer Paul N Baird Mary Varsamidis Lucy Busija Peter N Dimitrov Khin Zaw Aung Galina A Makeyeva Andrea J Richardson Lyndell Lim Liubov D Robman |
| author_facet |
Robyn H Guymer Paul N Baird Mary Varsamidis Lucy Busija Peter N Dimitrov Khin Zaw Aung Galina A Makeyeva Andrea J Richardson Lyndell Lim Liubov D Robman |
| author_sort |
Robyn H Guymer |
| title |
Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration. |
| title_short |
Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration. |
| title_full |
Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration. |
| title_fullStr |
Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration. |
| title_full_unstemmed |
Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration. |
| title_sort |
proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/af9016b6ce98442ab17214514f70a60a |
| work_keys_str_mv |
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| _version_ |
1718421522019778560 |