Marine omega-3 fatty acid supplementation and prevention of cardiovascular disease: Update on the randomized trial evidence

Abstract

To date, the VITamin D and OmegA-3 TriaL (VITAL) is the only large-scale randomized trial of marine omega-3 fatty acid (n-3 FA) supplementation for cardiovascular disease (CVD) prevention in a general population unselected for elevated cardiovascular risk. We review the findings of VITAL, as well as results from recent secondary prevention trials and updated meta-analyses of n-3 FA trials in the primary and secondary prevention of CVD. In VITAL, a nationwide sample of 25 871 US adults aged 50 and older, including 5106 African Americans, were randomized in a 2 × 2 factorial design to n-3 FAs (1 g/day; 1.2:1 ratio of eicosapentaenoic to docosahexaenoic acid) and vitamin D3 (2000 IU/day) for a median of 5.3 years. Compared with an olive oil placebo, the n-3 FA intervention did not significantly reduce the primary endpoint of major CVD events [composite of myocardial infarction (MI), stroke, and CVD mortality; hazard ratio (HR) = 0.92 (95% confidence interval 0.80-1.06)] but did significantly reduce total MI [HR = 0.72 (0.59-0.90)], percutaneous coronary intervention [HR = 0.78 (0.63-0.95)], fatal MI [HR = 0.50 (0.26-0.97)], and recurrent (but not first) hospitalization for heart failure [HR = 0.86 (0.74-0.998)]. The intervention neither decreased nor increased risk of atrial fibrillation. African Americans derived the greatest treatment benefit for MI and for recurrent hospitalization for heart failure (P interaction < 0.05 for both outcomes). Meta-analyses that include VITAL and high-risk or secondary prevention n-3 FA trials show coronary, but generally not stroke, risk reduction. More research is needed to determine which individuals may be most likely to derive net benefit. (VITAL clinicaltrials.gov identifier: NCT01169259).