In this RC trial omega-3 fat supplementation as margarine did not bring any benefit in patients with recent myocardial infarction

1. www.pronutritionist.net
n–3 Fatty Acids and
Cardiovascular Events after
Myocardial Infarction
Kromhout D et al.
N Engl J Med 2010; August 29.
(e-pub ahead of print)
Page 1 Kromhout D et al. N Engl J Med 2010; August 29.
(e-pub ahead of print)

2. Page 2
Background
• Resent studies have shown that supplementation
with eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) may reduce
– cardiovascular and all-cause mortality with patients with
cardiac disease (GISSI-Prevenzione Investigators 1999)
– the risk of fatal coronary heart disease (JELIS Study, only
EPA supplementation, Yomoyoma et al. 2007)
• A protective effect of the plant-derived n−3 fatty acid
alpha-linolenic acid (ALA) is less studied
• Cohort studies have suggested that low doses of n−3
fatty acids should be sufficient to reduce
cardiovascular risk
Kromhout D et al. N Engl J Med 2010; August 29.
(e-pub ahead of print)
www.pronutritionist.net

3. Methods (1/2)
• double-blind, placebo-controlled trial
• n = 4837 (age 60-80 years)
– all had had a myocardial infarction and were
receiving state-of-the-art antihypertensive,
antithrombotic, and lipidmodifying therapy
– 78 % were men
• Patients were randomly assigned to four
groups:
– a margarine supplemented with a combination of
EPA and DHA
– a margarine supplemented with ALA
– a margarine supplemented with EPA–DHA and ALA
– a placebo margarine
Page 3 Kromhout D et al. N Engl J Med 2010; August 29.
(e-pub ahead of print)
www.pronutritionist.net

4. Methods (2/2)
• All patients were given placebo margarine during
the first 4 to 6 weeks after randomization
• Study duration was 40 months
• The primary end point:
– fatal and nonfatal cardiovascular events and cardiac
interventions
• Secondary end points:
– incident of cardiovascular disease
– fatal cardiovascular disease
– fatal coronary heart disease
– ventricular-arrhythmia -related events
– death from any cause
www.pronutritionist.netKromhout D et al. N Engl J Med 2010; August
29. (e-pub ahead of print)
4

5. Results (1/3)
• mean intake of trial margarine was 18.8±4.7 g per day
– 90.5% of the patients consumed a mean of 20.6±2.8 g per day
• patients in EPA–DHA groups received
– 226 mg of EPA and 150 mg of DHA per day
• Baseline intake of EPA-DHA was 120-130 mg per day
• patients in ALA groups received
– 1.9 g of ALA per day
• Adverse effects did not differ between the groups
Page 5 Kromhout D et al. N Engl J Med 2010; August 29.
(e-pub ahead of print)
www.pronutritionist.net

6. Results 2/3
www.pronutritionist.netKromhout D et al. N Engl J Med 2010; August
29. (e-pub ahead of print)
6
P=0.93
P=0.20
All treatments provided as margarines

7. Results (3/3)
• Low-dose supplementation with EPA–DHA or
ALA did not significantly reduce the rate of
major cardiovascular events
– However, there was a 27% reduction in major
cardiovascular events with ALA among women vs
EPA-DHA or placebo
• Patients with diabetes had a higher risk of all
cardiovascular end points than did patients
without diabetes
www.pronutritionist.netKromhout D et al. N Engl J Med 2010; August
29. (e-pub ahead of print)
7

8. Discussion
• Previous randomized, controlled trials involving patients with
cardiac disease or at risk, did show protective effects of EPA,
either with or without DHA, on various composite
cardiovascular end points
• This discrepancy between those trials and current one may be
related to differences between patient populations in
– age
– sex distribution
– presence or absence of a history of coronary artery disease
• Authors did not speculate in their discussion if total intake of
EPA+DHA c. 500 mg (376 mg from margarine & dietary
baseline intake of 120-130 mg) was insufficient. In JELIS and
GISSI Prevenzione studies supplementation of EPA and DHA
was at least double (1 800 mg EPA and 850 mg EPA+DHA
respectively). It is possible that higher intake of omega-3 fatty
acids is required
Page 8 Kromhout D et al. N Engl J Med 2010; August 29.
(e-pub ahead of print)
www.pronutritionist.net