The antioxidant vitamins C and E

of high-dose AT supplementation on CVD outcomes in hemodialysis patients with
preexisting CVD. Hemodialysis patients with preexisting CVD (n = 196) aged 40–75
y at baseline from six dialysis centers were enrolled and randomly assigned to receive
800 IU/d RRR-AT (n = 97) or matching placebo (n = 99). Patients were followed for a
median of 519 d. The primary end point was a composite variable consisting of MI
(fatal and nonfatal), ischemic stroke, peripheral vascular disease (excluding the arteriovenous
fistula), and unstable angina. Secondary outcomes included each of the component
outcomes, total mortality, and CVD mortality. Lipid-adjusted AT levels were
monitored; they rose from 22.0 ± 7.7 µmol/L in the AT group to 27.8 ± 9.3 µmol/L
on-treatment and were unchanged in the placebo group (23.3 ± 10.7 µmol/L at baseline
and 20.2 ± 6.9 µmol/L on-treatment). Treatment with AT significantly decreased
primary cardiovascular end points (54% reduction in primary end point risk in the AT
group; P = 0.014). There was a 39% nonsignificant reduction in CAD mortality (RR,
0.61; 95% CI, 0.28–1.3; P = 0.25). Also, AT supplementation was associated with a
70% reduction in total MI rate (P = 0.016). Furthermore, treatment with AT was associated
with a 62% reduction in peripheral vascular disease but was not significant
(RR, 0.38; 95% CI, 0.1–1.4; P = 0.13). There were no significant differences between
the number of side effects reported for the placebo and AT groups. Thus, like
CHAOS, the SPACE study also reported a significant reduction in composite CVD
end points and MI with AT supplementation in patients with preexisting CVD. In
addition, plasma AT levels were measured in this study. Thus, it appears that higher
doses of AT (800 IU/d) would be beneficial for secondary prevention of CAD because
this dose exerts both antioxidant and anti-inflammatory effects.
Collaborative Group for the Primary Prevention Project (PPP)
In the Primary Prevention Project (PPP), the investigators followed 4495 people
with hypertension, hypercholesterolemia, diabetes, obesity, family history of premature
MI, or those who were elderly (25). The mean age of the patients was 64.4 y
and 58% were women. The patients were prescribed either aspirin (100 mg/d) or
all-rac-AT (300 mg/d). This was a 2 × 2 factorial design study with a mean followup
period of 3.6 y. The primary end point of this study was cardiovascular death,
nonfatal MI, and nonfatal stroke. In this study, aspirin lowered the frequency of all
end points, and was significant for cardiovascular death with a RR of 0.56
(0.31–0.99) and total cardiovascular events 0.77 (0.62–0.95). Also, severe bleeding
was more frequent in the aspirin group than in the nonaspirin group (1.1 vs. 0.3%; P
= 0.0008). However, AT supplementation had no benefit on the primary end point,
i.e., RR 1.07 (0.74–1.56), total cardiovascular events or disease 0.94 (0.77–1.16).
The investigators reported a benefit of AT therapy on peripheral artery disease, i.e.,
RR 0.54 (0.3–0.99). Thus, this study reported a 46% reduction in the incidence of
peripheral artery disease among patients taking vitamin E (P = 0.043). Like the
other clinical trials, this study suffers from certain weaknesses. There was no objective
measure of compliance, i.e., measurement of plasma AT or biomarkers of
oxidative stress and inflammation. Second, as the authors themselves point out, the
Copyright © 2002 AOCS Press