Elsevier

American Heart Journal

Volume 159, Issue 4, April 2010, Pages 539-546.e2
American Heart Journal

Trial Design
Effect of low doses of n-3 fatty acids on cardiovascular diseases in 4,837 post-myocardial infarction patients: Design and baseline characteristics of the Alpha Omega Trial

https://doi.org/10.1016/j.ahj.2009.12.033Get rights and content

Background

Weekly fish consumption has been related to a lower risk of fatal coronary heart disease (CHD) and incident stroke in populations with a low fish intake. This relation has mainly been attributed to n-3 fatty acids in fish, that is, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). It is at present unclear whether α-linolenic acid (ALA), a n-3 fatty acid from vegetable origin, could also be protective against cardiovascular diseases (CVDs). There is a need for food-based trials to establish the efficacy of low doses of n-3 fatty acids in CVD prevention.

Objectives

The aim of the study was to evaluate the effect of an additional daily intake of 400 mg of EPA + DHA and 2 g of ALA on CVD morbidity and mortality in free-living subjects with a history of myocardial infarction.

Design

The multicenter Alpha Omega Trial is a randomized, double-blind, placebo-controlled trial with a 2 × 2 factorial design. Between May 2002 and December 2006, we enrolled a total of 4,837 men and women aged 60 through 80 who experienced a myocardial infarction within 10 years before entering the study. Subjects were randomized to 1 of 4 margarine spreads that were enriched with EPA + DHA and/or ALA, or placebo. Compliance was monitored via tub counts and assessment of n-3 fatty acids in plasma. Subjects were observed for 40 months for the occurrence of fatal and nonfatal CVD.

Results

The cohort was on average 69 years old at the start of the study and comprised 22% women. Subjects had their (last) myocardial infarction approximately 4 years before enrolment. Mean body mass index was 27.7 kg/m2, and 17% smoked. Average serum total and high-density lipoprotein cholesterol were 4.7 and 1.3 mmol/L, respectively, and 85% used statins. Mean blood pressure was 142/80 mm Hg, and most subjects were on antihypertensive medication (88%). Diabetes mellitus was reported by 17% of the subjects, and 7% reported a history of stroke. The overall mortality rate during the trial period was 23 per 1,000 person-years, with approximately 40% due to CVD.

Current status

Follow-up of the patients was completed in November 2009, and findings will be reported in the second part of 2010.

Section snippets

Study design

The Alpha Omega Trial is a multicenter, double-blind, placebo-controlled trial with a parallel 2 × 2 factorial design resulting in 4 treatment groups (Figure 1). Subjects were enrolled in the trial from April 2002 to December 2006 and randomly assigned to different margarine spreads that provided low doses of n-3 fatty acids or placebo (described in more detail below), for a period of 40 months. Dosages are comparable to the Recommended Dietary Intakes for these n-3 fatty acids, namely

Results—Baseline characteristics of the cohort

Baseline characteristics of the cohort of the Alpha Omega Trial are shown in Table V. The cohort included 3,783 men (78%) and 1,054 women (22%), and most subjects (98.6%) were white. Subjects were on average 69 years old. Ten randomized patients did not meet the inclusion criterion for age, that is, one subject was aged 58 and 9 subjects were aged 59 at entry. The median period between the last MI and entry into the study was 3.7 years (Q1-Q3 1.7-6.3 years). For >90% of the subjects, a verified

Discussion

The Alpha Omega Trial is the first food-based double-blind intervention study in which low doses of n-3 fatty acids (ie, intakes within the normal dietary range) are studied in relation to fatal and nonfatal CVD. The n-3 fatty acids were administered through enriched margarine spreads. Trials of low doses of n-3 fatty acids are still feasible in the Netherlands because n-3 enriched foods are only now entering the market and dietary supplements are not widely consumed. Furthermore, Dutch people

Disclosures

Funding sources: Netherlands Heart Foundation (grant no. 2000T401), US National Institutes of Health (NIH/NHLBI and ODS, grant no. R01HL-076200) and Unilever R&D, Vlaardingen.

Author contributions: JMG coordinated the Alpha Omega Trial, contributed to the design of the study, obtained funding and drafted the manuscript; EJG contributed to the design of the study and provided medical supervision of the Alpha Omega Trial; EGS contributed to the design of the study and cosupervised the data

Acknowledgements

The authors express their gratitude to Eveline Waterham, Janny Heijstee, Marianne Pluigers, and Lucy Okma for their valuable contribution to data collection and administrative support. We thank Betty van der Struijs and Pieter Versloot for fatty acid analyses and Els Siebelink for processing of dietary data. Herbert van de Heuvel (LOF B.V., Egmond aan den Hoef) and Nicolette Mak (Valid Express, Amsterdam) are gratefully acknowledged for margarine distribution.

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    Clinical trial registration: ClinicalTrials.gov no. NCT00127452.

    d

    Members of the Alpha Omega Trial Group are listed in Appendix B.

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