Administering low-dose supplements of n-3 fatty acids—eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or alpha-linolenic acid (ALA)—did not significantly alter the rates of major cardiovascular (CV) events among MI patients, according to the results of the Alpha Omega trial presented this week at the European Society of Cardiology (ESC) meeting in Stockholm, and simultaneously published online Aug. 29 in the New England Journal of Medicine.
“n-3 fatty acids may prevent ventricular arrhythmias in patients who have had a myocardial infarction. Basic research has shown that enrichment of myocardial membranes with these fatty acids reduces the vulnerability to cardiac arrhythmias,” the authors wrote. “However, in controlled trials involving patients with cardiac disease who had implantable cardioverter-defibrillators, high doses of EPA acid and DHA (ranging from 0.9 to 2.6 g per day) did not significantly reduce the rates of ventricular arrhythmias.”
Dean Kromhout, PhD, of Wageningen University in Wageningen, the Netherlands, and colleagues sought to evaluate whether low doses (400 mg per day) of EPA/DHA or ALA at 2 g per day, or both, reduced the rates of cardiovascular events in 4,837 MI patients.
During the trial, which took place at 32 sites in the Netherlands between April 2002 and December 2006, patients were randomly assigned to receive the aforementioned doses of n-3 fatty acids or placebo, and were followed by researchers for 40 months.
Of the 4,837 patients enrolled, 78.2 percent were men. 21 percent of patients enrolled had diabetes, 97.5 percent were taking antithrombotic agents, 89.7 percent took antihypertensive drugs, 86 percent lipid-lower therapy and 3 percent antiarrhythmic drugs.
The researchers reported that 225 of the patients reported utilizing some type of n-3 fatty acid supplement during the trial.
For the first four to six weeks of the trial, patients were all administered placebo margarine. Subsequently, patients received either placebo margarine, margarine with 400 mg of EPA/DHA daily, 2 g of ALA daily or a combination of EPA/DHA and ALA.
The patients’ usual regimen of margarine was replaced with study margarine and they received eight tubes (250 g) of margarine every 12 weeks during the study period.
At baseline, the researchers measured the anthropometric measurements, blood pressure and heart rates of patients. The researchers used major adverse coronary event (MACE) rates as the trial's endpoint: (CV disease, fatal CV disease, fatal coronary heart disease and ventricular-arrhythmia-related events).
Kromhout and colleagues reported that the mean intake of trial margarine was 18.8 g per day and 90.5 percent of the patients adhered to the trial protocol and consumed a mean of 20.6 g per day.
The results showed that 13.9 percent of patients experienced a MACE event. Administration of EPA/DHA either alone or in combination with ALA, compared with ALA only or placebo had no significant effects on the rates of MACE seen during the trial, according to Kaplan-Meier curves.
But, the researchers did report that the study patients who received ALA saw 9 percent lower MACE events than patients administered placebo or EPA/DHA alone, 13.2 percent versus 14.5 percent, respectively.
For patients who received EPA/DHA and ALA, reductions in ventricular arrhythmia-related events decreased by 10 percent and 21 percent, respectively.
Additionally, the researchers reported that patients who received EPA/DHA had lower risk of experiencing fatal coronary heart disease compared with those administered placebo or ALA only, 2.8 percent versus 2.9 percent, respectively.
During a subgroup analysis, where researchers adjusted for sex, results showed a 27 percent reduction in MACE events among women administered ALA. Additionally, diabetic patients had a greater risk of all CV endpoints.
Although previous trials have shown that rates of cardiac disease diminished with EPA, with or without DHA, the low dose of EPA/DHA administered during the current trial had no significant effect on MACE events in patients with MI.
The researchers speculated that this may be due to differences in patients’ age, sex and a presence or absence of coronary artery disease.
“In conclusion, in this trial involving patients who had had an MI and who were receiving good clinical care, low doses of n-3 fatty acids did not significantly reduce the rates of cardiovascular endpoints,” the authors wrote.