To the Editor: In their randomized controlled trial, Dr Sesso and colleagues1 tested the hypothesis that antioxidant supplements could reduce the risk of a composite end point of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Patients were randomly allocated to antioxidant treatment (400 IU of vitamin E every other day or 500 mg of vitamin C daily) or to placebo and followed up for 8 years. During the follow-up neither vitamin E nor vitamin C reduced the risk of major cardiovascular events, suggesting that these supplements are not indicated to prevent atherosclerotic progression and its vascular complications. This finding is in line with the majority of interventional trials with antioxidants showing that antioxidants such as vitamins E and C are unable to influence vascular outcome in patients at risk of or with previous cardiovascular disease.2
However, potential confounding factors should be considered. Based on recent data suggesting that statins enhance the antioxidant properties of circulating vitamin E,3 we reviewed the trials of vitamin E to see how many patients concomitantly used statins and vitamin E.4 Among the 9 trials examined, 5 reported data on statin use. The concomitant use of statins was reported in at least one-third of the population screened, either on entry in the study or during the follow-up. In the Heart Protection Study,5 for instance, about 20% of vitamin E–allocated patients used statins at study entry; this figure reached values greater than 50% during the follow-up. Therefore, it is possible that these trials were biased by the concomitant use of statins. Assuming that patients included in these studies could have potentially benefited from vitamin E supplementation because of enhanced oxidative stress, the concomitant use of a statin may have rendered vitamin E supplementation unnecessary if it normalized vitamin E plasma levels.
In the study by Sesso et al,1 it is possible that many patients were treated with statins because of hypercholesterolemia (>35%) or history of cardiovascular disease (>5%) or diabetes (>6%), but no data were provided. Therefore, the authors should report data on concomitant statin use to see whether this treatment was a potential confounding factor.
Financial Disclosures: None reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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