Placebo-controlled Primary Prevention Trial Research Articles

The Safety of Antioxidant Vitamins

Meyers et al¹recently reviewed the safety of antioxidant vitamins and asserted that the antioxidants are safe. Recent clinical studies, however, suggest that a more circumspect approach regarding their administration is warranted, especially since supplementation usage may be as high as 40% in the US population.¹ The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a randomized, 2×2 factorial trial of antioxidants in 29 133 Finnish middle-aged male smokers that was designed to test the efficacy of α-tocopherol (50 mg/d) and β-carotene (20 mg/d) in the prevention of lung cancer, demonstrated an apparent excess of deaths from lung cancer and ischemic heart disease in those treated with β-carotene.²In addition, there was a possible increased risk of hemorrhagic stroke in the α-tocopherol— treated group when compared with the placebo-treated group. The Beta-Carotene and Retinol Efficacy Trial, a multicenter, randomized, double-blind, placebo-controlled primary prevention trial involving 18314 smokers, former smokers, and

Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease

Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo. A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years. After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

HMG CoA Reductase Inhibitors and Quality of Life

<h3>To the Editor.</h3> —The Air Force Coronary Atherosclerosis Prevention Study (AFCAPS) is an ongoing randomized, double-blind, placebo-controlled primary prevention trial to determine whether treatment with the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitor, lovastatin, will prevent coronary heart disease in persons with mild to moderate elevations of total and low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol levels. A total of 6605 participants without clinical evidence of coronary heart disease are enrolled, including men aged 45 to 73 years and women aged 55 to 73 years. Participants will be followed annually for total coronary heart disease events during a minimum of 5 years. A trial of this size and duration provides an opportunity to evaluate the long-term impact of cholesterol-lowering drug treatment on patient quality of life (QoL). In fact, it may be argued that it is imperative to assess the impact of long-term pharmacologic therapy on QoL in asymptomatic