Complementary Alternative Cardiovascular Medicine

62 Alternative Cardiovascular Medicine
infarction, stroke, or death from CVD (18). In a substudy of the HOPE
trial, Study to Evaluate Carotid Ultrasound changes in patients treated
with Ramipril and 400 IU vitamin E (SECURE), which lasted more than
4.5 yr, ramipril had a beneficial effect and vitaminE had a neutral effect
on atherosclerosis progression (19).
The GISSI-Prevenzione trial randomly assigned 11,324 patients who
survived recent (≤3 mo) myocardial infarction (MI) to supplements of
ω-3 fatty acids (1.0 g/d), vitamin E (300 mg), both, or placebo on top of
optimal pharmacological treatment and lifestyle advice (20). This was a
multicenter trial conducted in Italy for 3 to 5 yr. Supplements of ω-3 fatty
acids significantly decreased mortality and sudden death. Vitamin E had
no significant effects on cardiovascular deaths and /or nonfatal MI.
The Heart Protection Study (HPS) recently published (21) the findings
of a large trial with 20,536 UK adults (aged 40–80 yr) with coronary
disease, other occlusive arterial disease, or diabetes. The subjects were
randomly allocated to receive antioxidant vitamin supplementation
(600 mg vitamin E, 200 mg vitamin C, and 20 mg β-carotene daily) or
matching placebo in a 5-yr treatment period. Primary outcomes were
major coronary events (for overall analysis) and fatal or nonfatal vascular
events (for subcategory analyses), with subsidiary assessment of
cancer and other major morbidity. Although these vitamins increased
blood vitamin concentrations substantially, they did not show significant
differences in all-cause mortality or deaths resulting from vascular
and nonvascular causes. There were significant differences in nonfatal
MI or coronary death, nonfatal or fatal stroke, or coronary or noncoronary
revascularization. For the first occurrence of any of these “major vascular
events,” there were no differences. Among these high-risk subjects,
antioxidant vitamins were safe.
The HPS provided unequivocal evidence about the net effects of several
years of such treatment on total mortality among high-risk patients.
A “2 × 2 factorial” design was used to allow all patients to contribute
fully to the assessment of the separate effects of the cholesterol-lowering
drug and the vitamin supplement, as well as provide information about
their combined effects.
However, it can be argued that assessing the effect of antioxidants,
such as vitamin E, for a 4- to 6-yr period may not be long enough (22).
The findings for vitamin E in the Primary Prevention Project (PPP) could
be regarded as a false-negative result, because of the inadequate power
of a study that was stopped prematurely with the evidence of aspirin’s
benefit (23). The study was conducted in 4495 people with at least one
major recognized risk factor for CVD. This was a randomized con-