Cardiovascular disease, in particular coronary artery disease (CAD), remains the 
most important cause of morbidity and mortality in developed countries and, in 
the near future, more so in the developing world. Atherosclerotic plaque 
formation is the underlying basis for CAD. Growth of the plaque leads to 
coronary stenosis, causing a progressive decrease in blood flow that results in 
angina pectoris. Acute myocardial infarction and unstable angina were recently 
recognised as related to plaque rupture, not progressive coronary stenosis. 
Acute thrombus formation causes an abrupt coronary occlusion. The 
characteristics of the fibrin cap, contents of the plaque, rheological factors 
and active inflammation within the plaque contribute to plaque rupture. 
Oxidative processes are important in plaque formation. Oxidized low density 
lipoproteins (LDL) but not unoxidized LDL is engulfed by resident intimal 
macrophages, transforming them into foam cells which develop into fatty streaks, 
the precursors of the atherosclerotic plaque. Inflammation is important both in 
plaque formation and rupture. Animal studies have shown that antioxidants reduce 
plaque formation and lead to plaque stabilisation. In humans, high intakes of 
antioxidants are associated with lower incidence of CAD, despite high serum 
cholesterol levels. This observation suggests a role for inflammation in CAD and 
that reducing inflammation using antioxidants may ameliorate these processes. 
Men and women with high intakes of vitamin E were found to have less CAD. 
Vitamin E supplementation was associated with a significant reduction in 
myocardial infarction and cardiovascular events in the incidence of recurrent 
myocardial infarction. In the hierarchy of evidence in evidence-based medicine, 
data from large placebo-controlled clinical trials is considered necessary. 
Results from various mega-trials have not shown benefits (nor adverse effects) 
conferred by vitamin E supplementation, suggesting that vitamin E has no role in 
the treatment of CAD. These results do not seem to confirm, at the clinical 
level, the effect of antioxidants against active inflammation during plaque 
rupture. However, a closer examination of these studies showed a number of 
limitations, rendering them inconclusive in addressing the role of vitamin E in 
CAD prevention and treatment. Further studies that specifically address the 
issue of vitamin E in the pathogenesis of atherosclerosis and in the treatment 
of CAD need be performed. These studies should use the more potent antioxidant 
property of alpha-tocotrienol vitamin E.