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Randomized Trial of Aspirin and Cataracts in U.S. Physicians

Purpose | Background | Description | Patient Eligibility | Recruitment Status | Current Status | Results | Publications | Resource Centers | NEI Representative

Purpose

Background

Cataract is one of the most common causes of impaired vision as well as the third leading cause of blindness in the United States. Cataract surgery is one of the safest and most successful of all operations. The National Eye Institute has estimated that if the progression of cataract could be slowed enough to delay the need for surgery by even 10 years, the current annual number could be reduced by 45 percent.

Little is known about the relative importance of various potential risk factors in the development of cataract. Most current information on risk factors has come from anecdotal reports or from relatively small case-control studies. One major project, the Framingham Eye Study, has identified several factors that were significantly associated with subsequent cataract formation, including diabetes and dietary factors. Diabetes has long been thought to increase the risk of developing cataract.

Description

Recently, aspirin has been proposed as a drug that can prevent cataract formation or slow its progression. Aspirin may affect tryptophan levels in patients with cataract, or it may inhibit aldose reductase, an enzyme associated with the development of diabetic cataract. Thus, data from this study sought to determine whether one 325-mg aspirin tablet, taken on alternate days, protects against cataract formation. The data also sought to reveal other additional cataract risk factors that emerge after simultaneous controlling for other variables.

The other primary objective of this trial was to assess the antioxidant effects of beta-carotene (50 mg on alternate days) on cataract development. In addition, factors that have been suggested to be cataractogenic were assessed in prospective cohort studies. These factors included age, blood pressure, blood cholesterol, height, diabetes, medication use, cigarette smoking, and history of previous eye trauma or surgery. In addition, the possible associations between history of vitamin E and selenium intake and cataract were explored.

This trial was part of the Physicians' Health Study, an ongoing, randomized, placebo-controlled clinical trial of aspirin in the prevention of cardiovascular mortality and of beta-carotene in the prevention of cancer. Following randomization, each of the 22,071 physicians enrolled was assigned to one of four groups to take either aspirin or its placebo and beta-carotene or its placebo. Follow-up questionnaires were sent 6 and 12 months after randomization and every 12 months thereafter. The randomized aspirin component of the trial was terminated early (January 1988), after an average followup of approximately 5 years, because of a statistically extreme 44 percent reduced risk of a first myocardial infarction in the aspirin group.

Since this study is conducted by mail among physicians nationwide, examinations cannot be performed on all patients to determine when they have reached an end point. Reported diagnoses of cataract are confirmed by medical record review. The primary analysis will be of incidence of cataract in the aspirin and placebo groups. In addition, the Cox proportional hazards model will be used to determine whether there is a difference in time to cataract diagnosis between the two groups. It has been postulated that the potent antioxidant properties of beta-carotene might make it effective in preventing cataract development. The investigators will thus determine whether there is a difference in the numbers of cataracts between the beta-carotene/placebo groups and the aspirin/placebo groups.

Patient Eligibility

The study population consisted of 22,071 male U.S. physicians, aged 40 to 84 years in 1982, with no history of myocardial infarction, cancer, kidney disease, renal disease, or any other contraindication to the use of aspirin or beta-carotene, including regular use of corticosteroids.

Patient Recruitment Status

Recruitment began in April 1982 and was completed in December 1984.

Current Status of Study

Completed. This study was terminated in January 1988.

Results

There were 173 age-related cataracts among those physicians assigned to aspirin therapy and 180 among those given placebo (relative risk, 0.95; 95 percent confidence interval, 0.74 to 1.22). Cataract extractions were less frequent in the aspirin group than in the placebo group, but this difference was not statistically significant (relative risk 0.80; 95 percent confidence interval, 0.56 to 1.15). Among younger men (aged 40 to 59 years), the relative risks were 0.62 (95 percent confidence interval, 0.40 to 0.94) for cataract development and 0.67 (95 percent confidence interval, 0.38 to 1.31) for cataract extraction.

These randomized trial data tend to exclude any large benefit of aspirin. While the overall findings concerning cataract development seem to be null, the data on extraction of age-related cataract, while not statistically significant, cannot exclude possible small-to-moderate benefit of alternate-day aspirin therapy on the extraction of age-related cataract.

Publications

Glynn RJ, Christen WG, Bernheimer J, Manson JE, Hennekens CH: Body mass index: An independent predictor of cataract. Arch Ophthalmol 113: 1131-1137, 1995.

Christen WG, Glynn RJ, Seddon JM, Manson JE, Buring JE, Hennekens CH: Confirmation of self-reported cataract in the Physicians' Health Study. Ophthalmic Epidemiol 1: 85-91, 1994.

Manson JE, Christen WG, Seddon JM, Glynn RJ, Hennekens CH: A prospective study of alcohol consumption and risk of cataract. Am J Prev Med 10: 156-161, 1994.

Seddon JM, Christen WG, LaMotte FS, Manson JE, Glynn RJ, Buring JE, Hennekens CH: The use of vitamin supplements and the risk of cataract among U.S. male physicians. Am J Pub Health 84: 788-792, 1994.

Christen WG, Manson JE, Seddon JM, Glynn RJ, Buring JE, Rosner B, Hennekens CH: A prospective study of cigarette smoking and risk of cataract in men. JAMA 268: 989-993, 1992.

Seddon JM, Christen WG, Manson JE, Buring JE, Sperduto RD, Hennekens CH: Low dose aspirin and risk of cataract in a randomized trial of US Physicians. Arch Ophthalmol 109: 252-255, 1991.

Resource Centers

Chairman's Office
Charles H. Hennekens, M.D.
Brigham and Women's Hospital, Inc.
900 Commonwealth Avenue East
Boston, MA 02215
Telephone: (617) 732-4965
Fax: (617) 731-3843

Data Analysis Center
William Christen, Ph.D.
Brigham and Women's Hospital, Inc.
900 Commonwealth Avenue East
Boston, MA 02215
Telephone: (617) 278-0795
Fax: (617) 734-1437

NEI Representative

Maryann Redford, D.D.S., M.P.H.
National Eye Institute
National Institutes of Health
Executive Plaza South, Suite 350
6120 Executive Boulevard, MSC 7164
Bethesda, MD 20892-7164
Telephone: (301) 496-5983
Fax: (301) 402-0528
E-mail: maryann.redford@nei.nih.gov

Last Updated: 9/21/01



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