Abstract: Two RCTs with a total of 144 participants met the selection criteria. Both trials compared simvastatin versus placebo in older people (older than 50 or 60 years) with high risk of developing AMD (drusen present on examination). Overall, we judged the quality of the evidence to be low, as we downgraded all outcomes due to limitations in the designs of the trials and insufficient outcome reporting. The larger trial, with 114 participants, was conducted in Australia and used a higher dose (40 mg daily) of simvastatin for three years. Participants and study personnel in this trial were adequately masked, however data were missing for 30% of participants at three years' follow-up. The smaller trial, with 30 participants, was conducted in Italy and used a lower dose (20 mg) of simvastatin for three months. This trial reported insufficient details to assess the risk of bias. Neither trial reported data for change in visual acuity. Low-quality evidence from the smaller trial, with 30 participants, did not show a statistically significant difference between the simvastatin and placebo groups in visual acuity values at three months of treatment (decimal visual acuity 0.21 ± 0.56 in simvastatin group and 0.19 ± 0.40 in placebo group) or 45 days after the completion of treatment (decimal visual acuity 0.20 ± 0.50 in simvastatin group and 0.19 ± 0.48 in placebo group). The lack of a difference in visual acuity was not explained by lens or retina status, which remained unchanged during and after the treatment period for both groups. Preliminary analyses of 42 participants who had completed 12 months' follow-up in the larger trial did not show a statistically significant difference between simvastatin and the placebo groups for visual acuity, drusen score, or visual function (effect estimates and confidence intervals were not available). Complete data for these outcomes at three years' follow-up were not reported. At three years, low-quality evidence showed an effect of simvastatin in slowing progression of AMD compared with placebo to be uncertain (odds ratio 0.51, 95% confidence interval 0.23 to 1.09). One trial did not report adverse outcomes. The second trial reported no difference between groups in terms of adverse events such as death, muscle aches, and acute hepatitis. Evidence from currently available RCTs is insufficient to conclude that statins have a role in preventing or delaying the onset or progression of AMD.

Plain-language summary: We included two trials (144 total participants) in this review. Participants included men and women, most of whom were older than 50 years, who had good visual acuity. Participants were either susceptible to or had been diagnosed with an early stage of AMD. Both trials compared simvastatin with placebo. The larger trial, with 114 participants and conducted in Australia, used a higher dose of 40 mg per day and had a treatment period of three years. The smaller trial, with 30 participants and conducted in Italy, used a lower dose of 20 mg per day and had a treatment period of three months. The evidence provided in this review was up-to-date as of March 2016. Neither trial provided sufficient evidence to determine whether statins are effective in delaying the onset or progression of AMD. Information was lacking for outcomes related to vision, quality of life, and adverse events. The overall quality of the evidence was low. In the smaller trial, the number of participants enrolled and the short treatment period may not have been sufficient for detecting the effect of statins on AMD, which develops over time. In the larger trial, 30% of participants did not attend the three-year follow-up visit, and the amount of missing data hindered our ability to draw any reliable conclusions for this trial.