Age-related maculopathy in a randomized trial of low-dose aspirin among USphysicians

Objective: To examine the development of age-related maculopathy (ARM) in a large-scale trial of low-dose aspirin treatment. Methods: The Physicians' Health Study I was a randomized, double-masked, pl acebo-controlled trial of low-dose aspirin (325 mg every other day) and bet a carotene (50 mg every other day) in the prevention of cardiovascular dise ase and cancer conducted among 22 071 US male physicians aged 40 to 84 year s in 1982. A total of 21216 participants did not report ARM at baseline, we re followed up for at least 7 years, and are included in this analysis. Main Outcome Measures: Total ARM, defined as a self-report confirmed by med ical record evidence of an initial diagnosis subsequent to randomization, a nd ARM with vision loss, defined as total ARM but with vision loss to 20/30 or worse attributable to ARM. Results: Early termination of the randomized aspirin component of the Physi cians' Health Study I, after an average of 60.2 months of treatment and fol low-up due to a statistically extreme 44% reduced risk of first myocardial infarction, resulted in a far lower number of incident cases of ARM during the aspirin treatment period than would have accrued without early terminat ion. Thus, during an average of 60.2 months of follow-up, a total of 117 ca ses of ARM were confirmed, including 57 cases responsible for vision loss t o 20/30 or worse. There were 51 cases of ARM in the aspirin group and 66 in the placebo group (relative risk, 0.77; 95% confidence interval, 0.54-1.11 ). For ARM, with vision loss, there were 25 cases in the aspirin group and 32 in the placebo group (relative risk, 0.78; 95% confidence interval, 0.46 -1.32). Conclusions: These randomized trial data tend to exclude any large benefici al effect of 5 years of low-dose aspirin treatment on ARM. However, a small er, but potentially important, beneficial effect cannot be ruled out and wo uld require testing in randomized trials of adequate size and duration.