Randomised Controlled Trial of Vitamin E in Patients with
Coronary Disease: Cambridge Heart Antioxidant Study (CHAOS)
Randomised Controlled Trial of Vitamin E in Patients with Coronary Disease: Cambridge Heart Antioxidant Study (CHAOS)
Stephens NG; Parsons A; Schofield PM;
Kelly F; Cheeseman K; Mitchinson MJ.
Lancet, 1996 Mar 23, 347(9004):781-6. Pub type:
Clinical Trial; Journal Article; Randomized Controlled Trial
Abstract:
BACKGROUND:
Vitamin
E (alpha-tocopherol) is thought to have a role in prevention of
atherosclerosis, through inhibition of oxidation of low-density
lipoprotein. Some epidemiological studies have shown an
association between high dietary intake or high serum
concentrations of alpha-tocopherol and lower rates of ischaemic
heart disease.
We tested the hypothesis that treatment with a high dose of alpha-tocopherol would reduce subsequent risk of myocardial infarction (MI) and cardiovascular death in patients with established ischaemic heart disease.
METHODS:
In this double-blind, placebo-controlled study with stratified
randomisation, 2002 patients with angiographically proven
coronary atherosclerosis were enrolled and followed up for a
median of 510 days (range 3-981). 1035 patients were assigned
alpha-tocopherol (capsules containing 800 IU daily for first 546
patients; 400 IU daily for remainder); 967 received identical
placebo capsules. The primary endpoints were a combination of
cardiovascular death and non-fatal MI as well as non-fatal MI
alone.
FINDINGS:
Plasma
alpha-tocopherol concentrations (measured in subsets of patients)
rose in the actively treated group (from baseline mean 34.2
micromol/L to 51.1 micromol/L with 400 IU daily and 64.5
micromol/L with 800 IU daily) but did not change in the placebo
group. Alpha-tocopherol treatment significantly reduced the risk
of the primary trial endpoint of cardiovascular death and
non-fatal MI (41 vs 64 events; relative risk 0.53 [95% Cl
0.34-0.83; p=0.005). The beneficial effects on this composite
endpoint were due to a significant reduction in the risk of
non-fatal MI (14 vs 41; 0.23 [0.11-0.47]; p=0.005); however,
there was a non-significant excess of cardiovascular deaths in
the alpha-tocopherol group (27 vs 23; 1.18 [0.62-2.27]; p=0.61).
All-cause mortality was 36 of 1035 alpha-tocopherol-treated
patients and 27 of 967 placebo recipients.
INTERPRETATION:
We
conclude that in patients with angiographically proven
symptomatic coronary atherosclerosis, alpha-tocopherol treatment
substantially reduces the rate of non-fatal MI, with beneficial
effects apparent after 1 year of treatment. The effect of
alpha-tocopherol treatment on cardiovascular deaths requires
further study.
