Vitamin E: as in effective?

Vitamin E seems to have practically become a standard among my patients. This week I heard Dr. Zorba Paster endorse its use during his popular call-in public radio talk show, Zorba Paster on Your Health. A wellness newsletter from the University of California at Berkeley and academic cardiologists at continuing medical education presentations have encouraged its use. The New England Journal of Medicine has published correspondence encouraging widespread use.1 But does it work? In this Evidence Matters, I review the three randomized trials of high-dose vitamin E for secondary prevention of coronary heart disease: CHAOS (Cambridge Heart Antioxidant Study, GISSI (Gruppo Italiano per lo Studio della Spravivenza nell’Infarto Miocardio), and HOPE (Heart Outcomes Prevention Evaluation). The enthusiasm for vitamin E use was fueled by the publication of the CHAOS results 4 years ago. After a rather short follow-up period, nonfatal myocardial infarction (MI) was reduced in patients assigned to vitamin E. Of patients receiving vitamin E, 1.4% had an MI compared with 4.2% of those receiving placebo. These results seem phenomenal if reported as a reduction in relative risk (RR) (77% lower risk with vitamin E use). However, it has been shown that focusing on RR reduction promotes acceptance of therapies more than when absolute risk benefits are reported.2, 3 So, note carefully that fewer than 3% of patients seemed to have been spared an infarction. Finally, one of the tenets of evidence-based medicine is that all relevant outcomes must be examined. In this regard, CHAOS falls short of confirming vitamin E’s benefit: It failed to positively impact mortality. For these reasons, the CHAOS results were actually inconclusive. Nonetheless, the impressive RR reduction for MI associated with vitamin E use in CHAOS was, I believe, a factor in the increasing popularity of vitamin E supplementation. Thanks to the GISSI and the HOPE investigators, in the past year we have been given data that are more conclusive. These trials included more patients, lasted longer, and reported a larger number of events. Unfortunately, the magic bullet—a vitamin supplement that would provide a simple, easy way to improve heart disease outcomes—has remained elusive. The GISSI investigators, in contrast to the CHAOS investigators, found no effect whatsoever on nonfatal cardiovascular events. Furthermore, despite including twice as many patients as the CHAOS investigators, they found no mortality benefit from vitamin E. The HOPE study used the more rigorous placebo-controlled, double-blind trial design, and again, vitamin E conferred no benefit. These results are important for two reasons. First, with more and more effective secondary prevention strategies for atherosclerotic disease, it is becoming increasingly important for patients not to be distracted by useless strategies. Some