Evidence for the effect of omega-3 fatty acids on cardiovascular risk has been inconsistent. While some systematic reviews have found little or no evidence that dietary or supplementary omega-3 fatty acid intake alters the risk of death or cardiovascular events in primary or secondary prevention (Cochrane Database Syst Rev 2004 Oct 18;(4):CD003177,  Arch Intern Med 2012 Apr 9 early online), others have shown some benefit for cardiac mortality (BMJ 2008 Dec 23;337:a2931, Ann Med 2009;41(4):301). The recently reported ORIGIN trial examined the effects of supplementation in 12,611 patients with impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes. 

Patients > 50 years old (mean age 64 years, 88% with diabetes) were randomized to omega-3 fatty acids 1 g orally once daily (Omacor capsule, sold in United States as Lovaza) vs. placebo. All patients had preexisting cardiovascular disease (myocardial infarction, stroke, or revascularization in 59%) or cardiovascular risk factors at baseline. Patients were also randomized to open-label insulin glargine vs. standard care (with results reported in a companion publication). These groups were pooled for the primary analysis of the effects of omega-3 supplementation.

At median follow-up of 6.2 years, there were no significant differences between groups in cardiovascular mortality (9.1% vs. 9.3%) or all-cause mortality (15.1% vs. 15.4%) (level 1 [likely reliable] evidence). There were also no significant differences in fatal and nonfatal myocardial infarction, fatal and nonfatal stroke, heart failure-related hospitalization, or revascularization procedures. Omega-3 supplementation was associated with significant reduction in triglyceride levels (p < 0.001), but had no significant effect on other lipid levels. In subgroup analyses, supplementation had no significant effect on cardiovascular mortality in either the insulin glargine or standard care groups (N Engl J Med 2012 Jul 26;367(4):309).