| Abstract
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Background:
Results from prospective cohort studies and randomized, controlled trials
have provided evidence of a protective effect of n-3 fatty acids against
cardiovascular diseases. We examined the effect of the marine n-3 fatty
acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and of
the plant-derived alpha-linolenic acid (ALA) on the rate of cardiovascular
events among patients who have had a myocardial infarction.
Methods: In a multicenter, double-blind, placebo-controlled trial, we
randomly assigned 4837 patients, 60 through 80 years of age (78% men),
who had had a myocardial infarction and were receiving state-of-the-art
antihypertensive, antithrombotic, and lipid-modifying therapy to receive
for 40 months one of four trial margarines: a margarine supplemented with
a combination of EPA and DHA (with a targeted additional daily intake
of 400 mg of EPA–DHA), a margarine supplemented with ALA (with a
targeted additional daily intake of 2 g of ALA), a margarine supplemented
with EPA–DHA and ALA, or a placebo margarine. The primary end point
was the rate of major cardiovascular events, which comprised fatal and
nonfatal cardiovascular events and cardiac interventions. Data were analyzed
according to the intention-to-treat principle, with the use of Cox proportional-hazards
models.
Results: The patients consumed, on average, 18.8 g of margarine per day,
which resulted in additional intakes of 226 mg of EPA combined with 150
mg of DHA, 1.9 g of ALA, or both, in the active-treatment groups. During
the follow-up period, a major cardiovascular event occurred in 671 patients
(13.9%). Neither EPA–DHA nor ALA reduced this primary end point (hazard
ratio with EPA–DHA, 1.01; 95% confidence interval [CI], 0.87 to 1.17;
P=0.93; hazard ratio with ALA, 0.91; 95% CI, 0.78 to 1.05; P=0.20). In
the prespecified subgroup of women, ALA, as compared with placebo and
EPA–DHA alone, was associated with a reduction in the rate of major
cardiovascular events that approached significance (hazard ratio, 0.73;
95% CI, 0.51 to 1.03; P=0.07). The rate of adverse events did not differ
significantly among the study groups.
Conclusions: Low-dose supplementation with EPA–DHA or ALA did not
significantly reduce the rate of major cardiovascular events among patients
who had had a myocardial infarction and who were receiving state-of-the-art
antihypertensive, antithrombotic, and lipid-modifying therapy. (Funded
by the Netherlands Heart Foundation and others; ClinicalTrials.gov number,
NCT00127452.)
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