AREDS results show sustained treatment benefit for AMD

AREDS is a prospective natural history study that also was a randomized, multicenter, double-masked, placebo-controlled evaluation of the AREDS formulation of high-dose antioxidants and zinc in 4,757 participants. This randomized portion of the study ended in 2001. A total of 3,687 participants were followed for an additional 5 years to determine the long-term progression rates to advanced AMD and moderate vision loss, Dr. Chew explained. She is deputy director, Division of Epidemiology and Clinical Research, National Eye Institute, National Institutes of Health, Bethesda, MD.

The participants had been assigned randomly to receive either antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg), zinc, 80 mg as zinc oxide and copper as 2 mg as cupric oxide; antioxidants plus zinc; or placebo. Dr. Chew reported the results for the participants with category 2, 3, and 4 disease (those with multiple small and nonextensive intermediate drusen; those with at least extensive intermediate drusen or large drusen with no evidence of advanced AMD in either eye; and those with advanced AMD in one eye, respectively) who were at higher risk of progression.

"The placebo group at 5 years after treatment had a 28% risk of developing advanced AMD, compared with a 20% risk with the combination treatment," Dr. Chew added. "This translates into a 25% reduction in the risk of progression to advanced AMD."

Persistent effect

The most important finding of this study is that the treatment effect persisted 10 years after the start of the study.

"Ten years after treatment in the placebo group, 44% of patients developed advanced AMD compared with 34% of patients who received the combination treatment consisting of antioxidant vitamins and zinc with copper," Dr. Chew said. "This translates into a 27% reduction in the risk of progression to advanced AMD."

Although the patients no longer are assigned randomly to a particular treatment, they all have been counseled about continuing to take the formulation of minerals and vitamins. The rate of moderate vision loss also was lower in the group randomly assigned to combination treatment compared with the placebo group, 44% versus 56%, respectively.

The results also showed no beneficial treatment effect on the early stages of AMD, and the AREDS formulation did not prevent progression of drusen.

No increased mortality was observed in patients taking the AREDS formulation of minerals and vitamins; patients randomly assigned to zinc alone had a decreased risk of mortality.

"The clinical significance of this last finding is unknown," Dr. Chew said.

The beneficial effect of this formulation of antioxidants and zinc persisted for at least 10 years of follow-up, according to Dr. Chew. No beneficial effects were found in patients with early stages of AMD, and no increase in mortality was seen in patients taking the AREDS formulation, she said.

"We recommend the AREDS formulation to participants with extensive intermediate drusen or large drusen in both eyes and patients with advanced AMD in one eye," she said. "The median treatment of 6.5 years appeared to continue to impart a protective effect 10 years later."