Proof of Concept, Randomized, Placebo-Controlled Study of the Effect of Simvastatin on the Course of Age-Related Macular Degeneration
Proof of Concept, Randomized, Placebo-Controlled Study of the Effect of Simvastatin on the Course of Age-Related Macular Degeneration
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DOI：
10.1371/journal.pone.0083759
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发表时间：
2013-12-31
期刊：
影响因子：
3.7
通讯作者：
Robman, Liubov D.
中科院分区：
文献类型：
--
作者：
Guymer, Robyn H.;Baird, Paul N.;Robman, Liubov D.
背景资料：HMG辅酶A还原酶抑制剂是无处不在的，在我们的社会，但他们在年龄相关性黄斑变性（AMD）的潜在作用仍有待determined.Methodology/主要调查结果：目的：评价辛伐他汀对AMD进展的影响和载脂蛋白E（ApoE）和补体因子H（CFH）基因多态性的影响修改。设计：一项概念验证双盲随机对照研究。参会人员：114名年龄在53至91岁之间的参与者，患有双侧中度AMD或单侧非晚期AMD（对侧眼患有晚期AMD），至少一只眼睛的BCVA >= 20/60，血脂正常。干预：辛伐他汀40 mg/天或安慰剂，1：1分配。主要结果测量：AMD进展为晚期AMD或非晚期AMD的严重程度。结果安慰剂组AMD的累积进展率为70%，辛伐他汀组为54%。根据年龄、性别、吸烟和基线AMD严重程度调整的意向治疗多变量logistic回归分析显示，辛伐他汀组的进展风险显著降低2倍：OR 0.43（0.18-0.99），p = 0.047。按基线AMD严重程度分层的事后分析显示，在入组前对侧眼患有晚期AMD的患者中，治疗没有获益：OR 0.97（0.27-3.52），p = 0.96，调整年龄、性别和吸烟后。然而，与安慰剂组相比，双侧中度AMD组的进展风险显著降低[校正OR 0.23（0.07-0.75），p = 0.015]。在CFH基因的CC（Y 402 H）风险基因型中观察到最显著的效果[OR 0.08（0.02-0.45），p = 0.004]。辛伐他汀干预的危害没有证据detected.Conclusion/Significance：辛伐他汀可以减缓非晚期AMD的进展，特别是对于那些有风险的CFH基因型CC（Y 402 H）。进一步探索他汀类药物治疗AMD的潜在用途，重点是遗传亚组，是必要的。
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.