The Alpha Omega Trial was a randomized double-blind placebo-controlled trial carried out in 4,837 patients with a history of myocardial infarction to test the the hypothesis that low doses of omega-3 fatty acids could reduce major cardiovascular events, in particular fatal coronary events.
The justification for the Alpha Omega Trial
In 1985 Kromhout et al. showed that eating fish once or twice a week was associated with a 50% lower risk of fatal coronary heart disease in the Zutphen Study. That result was confirmed in various other cohort studies in The Netherlands and in other countries. In 1994 we observed an inverse association between fish consumption and the incidence of stroke in the Zutphen Study that was also confirmed in other cohort studies.
The most likely explanation for these associations was a protective effect of the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish against cardiovascular events, in particular fatal cardiac arrhythmias.
The aim of the Alpha Omega Trial
The main aim of the Alpha Omega Trial was to examine whether major cardiovascular events, in particular fatal coronary heart disease, could be prevented by low doses of the fish fatty acids EPA and DHA in patients with a history of myocardial infarction. In addition, the effect of the plant-based omega-3 fatty acid alpha-linolenic acid (ALA) was studied. If ALA would prevent cardiovascular events, eating plant foods rich in ALA could be a substitute for eating fish.
Primary and secondary endpoints
The primary end point of this trial was major cardiovascular events, which comprised fatal and nonfatal cardiovascular disease and the cardiac interventions PCI and CABG. Secondary end points were incident cardiovascular disease, fatal cardiovascular disease, fatal coronary heart disease, ventricular-arrhythmia–related events (sudden death, fatal and nonfatal cardiac arrest, and placement of implantable cardioverter–defibrillators), and death from any cause.
Timeline of the Alpha Omega Trial
The trial started in May 2002 with a pilot study of 3 months and the inclusion of patients was closed in December 2006. The active intervention period of ~40 months was preceded by a placebo period of 6 weeks. At baseline, anthropometric measures were assessed, and blood pressure and heart rate were measured. In addition, nonfasting blood samples were obtained for the measurement of serum lipid and plasma glucose levels. Demographic factors, lifestyle characteristics, and medication and medical histories were assessed with the use of questionnaires.
Baseline examinations were repeated after 20 months in a random sample of 810 patients and after 40 months in the 2531 patients (52.3%) who completed the trial before January 1, 2009. Owing to budget constraints, assessments of the remainder of the cohort were made with the use of questionnaires regarding demographic factors, lifestyle characteristics, and medication and medical histories that were mailed to the patients. Trained research staff performed structured telephone interviews with more than 90% of the cohort 12 and 24 months after the start of the intervention to collect data on adherence, cardiovascular events, adverse events, changes in medication, intake of fish, and use of n−3 fatty acid supplements.