Randomized clinical trial France DMLA2: effect of trimetazidine on exudative and nonexudative age-relatedmacular degeneration.

ABSTRACT

PURPOSE: To evaluate the effect of trimetazidine (TMZ) in a randomized, double-blind, placebo-controlled clinical trial on the occurrence of choroidal neovascularization or geographic atrophy in age-related macular degeneration. METHODS: A total of 1,086 patients from France, Belgium, and Spain with soft drusen and/or retinal pigment epithelium abnormalities in the study eye and choroidal neovascularization in the contralateral eye were randomly assigned to receive orally placebo or TMZ 70 mg daily (35 mg × 2) and followed-up for 3 years to 5 years. RESULTS: Treatment duration ranged between 0.4 months and 67.8 months with a mean ± SD of 38 ± 16 months. Three hundred and fifty-eight patients developed choroidal neovascularization (incidence per 100 patient-years TMZ 10.86; placebo 11.13). Trimetazidine did not prevent the choroidal neovascularization (hazard ratio = 0.97; 95% confidence interval, 0.77-1.20; P = 0.781). However, there was a trend favoring TMZ for retinal atrophy, a secondary endpoint (HR = 0.76; 95% confidence interval, 0.56-1.02; P = 0.069). Overall, the difference in atrophy incidence between TMZ and placebo was not statistically different. Differences within some prespecified subgroups of patients showed superiority of TMZ in men (HR = 0.50; 95% confidence interval, 0.28-0.89; p = 0.016), in patients aged ≤75 years (HR = 0.58; 95% confidence interval, 0.38-0.88; p = 0.010), or in patients presenting with isolated pigmentary changes (HR = 0.19; 95% confidence interval, 0.05-0.70; p = 0.005). CONCLUSION: Trimetazidine failed to prevent choroidal neovascularization. Subgroup analyses suggest that this drug could be tested as preventive therapy for geographic atrophy, although the overall comparison showed no statistically significant differences in the progression of geographic atrophy.