None listed
Conditions
Brief summary
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.
Interventions
Two tablets of simvastatin, 20 mg each, daily. The planned duration of the intervention/control is five years.
Sponsors
Centre for Eye Research Australia
Study design
Allocation
Randomised controlled trial
Intervention model
Single group
Primary purpose
Prevention
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(1) The ability to assess the macula in at least one eye, (2) VA better than or equal to 6/18 in the study eye(s). (3) High risk drusen in both eyes: one or more large soft druse (125 microns), or >10 intermediate drusen (62.5 microns) ORLate AMD (CNV, GA) in one eye and any drusen or pigment change in the study eye.Note: the study eye is allowed to have non-central GA and/or non-neovascular PED (4) cholesterol level within the normal limits according to the person's medical history (5) not currently on any cholesterol-lowering medication.
Exclusion criteria
(1) Medical and ophthalmic conditions which potentially affects visual function, including visually significant cataract (as defined by WILMER's grading method-that is nuclear opacity score of 2.00 or greater, cortical opacity score of greater than 3, any posterior subcapsular cataract), history of diabetes and glaucoma(2) Use of medications which may affect visual function, such as plaquenil, chloroquine, major tranquilizers.(3) cholesterol levels outside the normal limits given person's medical history.(a)Existing coronary heart disease:-- cholesterol > 4 mmol/L(b) Diabetics, people with hypertension, peripheral vascular disease, family history of hypercholesterolaemia or coronary heart disease:-- cholesterol > 6.5mmol/L or cholesterol > 5.5 if HDL <1.0mmol/L(c) people with HDL <1.0mmol/L:--cholesterol >6.5mmol/L(d) men aged 35 to 75 years or postmenopausal women up to 75 years:-- cholesterol >7.5 or triglycerides > 4.0mmol/L(e) people with none of the above:--cholesterol >9.0 or triglycerides >8.0mmol/L(4)Statins is clinically contraindicated:(a) Allergy(b) ALT > 2 times the upper limit of normal(c) Previous severe adverse reactions to statin.
Outcome results
None listed