The HOPE and HOPE-TOO Trial Investigators*
and epidemiological data suggest that vitamin E supplementation may
prevent cancer and cardiovascular events. Clinical trials have
generally failed to confirm benefits, possibly due to their
relatively short duration.
Objective To evaluate whether long-term
supplementation with vitamin E decreases the risk of cancer, cancer
death, and major cardiovascular events.
Design, Setting, and Patients A
randomized, double-blind, placebo-controlled international trial
(the initial Heart Outcomes Prevention Evaluation [HOPE] trial
conducted between December 21, 1993, and April 15, 1999) of patients
at least 55 years old with vascular disease or diabetes mellitus was
extended (HOPE–The Ongoing Outcomes [HOPE-TOO]) between April 16,
1999, and May 26, 2003. Of the initial 267 HOPE centers that had
enrolled 9541 patients, 174 centers participated in the HOPE-TOO
trial. Of 7030 patients enrolled at these centers, 916 were deceased
at the beginning of the extension, 1382 refused participation, 3994
continued to take the study intervention, and 738 agreed to passive
follow-up. Median duration of follow-up was 7.0 years.
Intervention Daily dose of natural source
vitamin E (400 IU) or matching placebo.
Main Outcome Measures Primary outcomes included
cancer incidence, cancer deaths, and major cardiovascular events
(myocardial infarction, stroke, and cardiovascular death). Secondary
outcomes included heart failure, unstable angina, and
Results Among all HOPE patients, there
were no significant differences in the primary analysis: for cancer
incidence, there were 552 patients (11.6%) in the vitamin E group vs
586 (12.3%) in the placebo group (relative risk [RR], 0.94; 95%
confidence interval [CI], 0.84-1.06; P = .30); for
cancer deaths, 156 (3.3%) vs 178 (3.7%), respectively (RR, 0.88; 95%
CI, 0.71-1.09; P = .24); and for major
cardiovascular events, 1022 (21.5%) vs 985 (20.6%), respectively
(RR, 1.04; 95% CI, 0.96-1.14; P = .34). Patients in
the vitamin E group had a higher risk of heart failure (RR, 1.13;
95% CI, 1.01-1.26; P = .03) and hospitalization for
heart failure (RR, 1.21; 95% CI, 1.00-1.47; P = .045).
Similarly, among patients enrolled at the centers participating in
the HOPE-TOO trial, there were no differences in cancer incidence,
cancer deaths, and major cardiovascular events, but higher rates of
heart failure and hospitalizations for heart failure.
Keywords: antiossidanti; prevenzione; vitamine; cancro; infarto; diabete.