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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)

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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)

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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)

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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)

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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)

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Results 2/3

www.pronutritionist.netKromhout D et al. N Engl J Med 2010; August 29. (e-pub ahead of print)

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P=0.93

P=0.20

All treatments provided as margarines

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)

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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)

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