excluding the high-dose trial (12 trials; N5119,298), patients in the supplementation group had a small but significant reduction in MI (rate ratio [RR], 0.92; 95% CI, 0.86-0.99), CHD death (RR, 0.92; 95% CI, 0.86-0.98), total CHD (RR, 0.95; 95% CI, 0.91-0.99), total stroke (RR, 1.05; 95% CI, 0.98-1.14), CVD death (RR, 0.93; 95% CI, 0.88-0.99), total CVD (RR, 0.97; 95% CI, 0.94-0.99), and major vascular events (RR, 0.97; 95% CI, 0.94-1.0) compared with placebo and control. Analysis including the highdose trial demonstrated a significant dose-response relationship: per every 1,000 mg/d marine omega-3 supplementation, a 9% reduction in MI (95% CI, 2-15) and 7% reduction in total CHD (95% CI, 0.1-13) were noted. All other outcomes measured were not significantly different between the supplementation groups and the placebo/control groups.A 2018 systematic review and meta-analysis of 79 RCTs (N5112,059) examined the effect of long-chain omega-3 fatty acid supplementation on CVD disease. 2 Patients in these studies had known CVD disease and were either treated as secondary (42%) or primary (58%) prevention, with pregnant and acutely ill patients excluded. Patients received varying long-chain omega-3 fatty acid doses with more than 90% of patients receiving 400 to 2,400 mg/d for between 12 and 72 months and were compared with placebo, different dietary advice, or no treatment. Compared with the control groups, patients who received omega-3 supplementation did not demonstrate a significant reduction in all-cause mortality (39 RCTs; N592,653; RR, 0.98; 95% CI, 0.93-1.03), CVD mortality (25 RCTs; N567,772; RR, 0.95; 95% CI, 0.87-1.03), or CVD events (38 RCTs; N590,378; RR, 0.99; 95% CI, 0.94-1.04). Chronic heart disease mortality, stroke, and arrhythmia were also not significantly different between the groups. A significant 7% reduction in CHD events was initially noted; however, after adjustment for bias, no significant difference in the omega-3 group was found compared with the controls for overall CHD events (12 RCTs; N530,227; RR, 0.97; 95% CI, 0.90-1.05).A 2017 evidence-based science advisory from The American Heart Association (AHA) gave no recommendation on the use of omega-3 polyunsaturated fatty acid supplementation for the primary prevention of CHD. 3 The AHA did not recommend treatment with omega-3 poly unsaturated fatty acids for the primary prevention of CHD in patients with diabetes or for those with risk factors for CVD (strength: Class III, no proven benefit). However, they did recommend supplementation as secondary prevention in patients with known CHD (strength: Class IIa, weight of evidence/opinion is in favor of usefulness/efficacy).