The consumption of fish or the use of n-3 fatty acid supplements has been shown to reduce triglyceride levels, which can potentially lead to a decrease in plaque formation and a decrease in cardiovascular risk. Epidemiologic studies support a beneficial effect of n-3 fatty acid supplementation; however, no effect was found on cardiovascular outcomes in a recently published meta-analysis reviewing only randomized, double blinded, placebo-controlled trials.1-4 Due to the conflicting evidence, the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial was designed to see if the use of n-3 fatty acids can reduce the primary outcome of cardiovascular event in patients with diabetes or at risk of diabetes (impaired glucose tolerance or impaired fasting glucose) and who are at high risk for cardiovascular (CV) events.5
The ORIGIN trial was a randomized, double blind, placebo-controlled trial with a 2-by-2 factorial design which enrolled 12,536 patients at least 50 years old with type 2 diabetes on none or one oral glucose-lowering agent, impaired fasting glucose (IFG), or impaired glucose tolerance (IGT), and who had cardiovascular disease or were at risk for cardiovascular disease. Patients were randomized to receive treatment with a 1-g capsule of n-3 fatty acid (Lovaza®) or a placebo capsule containing 1 gram of olive oil daily. Additionally, patients were randomized to receive insulin glargine or standard of care and the results of this comparison were published elsewhere. The primary outcome of the ORIGIN trial was death from cardiovascular events. The major secondary outcomes consisted of the composite endpoint of death from cardiovascular events, nonfatal MI, or nonfatal stroke; death from any cause; and death from arrhythmias.5
Most participants were male with an average age of 63 years. At baseline, cardiovascular disease was present in 59% and the mean hemoglobin A1C was 6.4% and median triglyceride level was 140-142 mg/dL. The investigators did not find any significant difference with the use of n-3 fatty acids for the primary endpoint of death caused by CV events (HR 0.98, CI, 0.87 to 1.10; P=0.72) after a median follow-up time of 6.2 years.5 No difference was also observed for the secondary composite outcome of MI, stroke, and death from cardiovascular causes (HR 1.01, CI, 0.93-1.10; P= 0.81). In addition, n-3 fatty acids did not have a significant impact on death from any cause (HR 0.98, CI, 0.89 to 1.07, P=0.63) and death from arrhythmia (HR 1.10, CI, 0.93 to 1.30; P=0.26).5 The only significant difference that was observed between the two groups was a reduction of triglyceride levels (mean reduction of 14.5 mg/dL) for patients receiving n-3 fatty acids (P <0.01).5
The ORIGIN trial found no benefit of n-3 fatty acid supplementation on cardiovascular events in high risk patients despite a significant reduction in triglycerides. The strengths of the ORIGIN trial are its large sample size, long duration, and inclusion of only patients with dysglycemia and at high risk for CV events. The dose of 1 gm daily ...