Negative Lovaza (ethyl esters of n-3 fatty acids) Study. See GOED Discussion* below.
Background The use of n-3 fatty acids may prevent cardiovascular events in patients with recent myocardial infarction or heart failure. Their effects in patients with (or at risk for) type 2 diabetes mellitus are unknown.
Methods In this double-blind study with a 2-by-2 factorial design, we randomly assigned 12,536 patients who were at high risk for cardiovascular events and had impaired fasting glucose, impaired glucose tolerance, or diabetes to receive a 1-g capsule containing at least 900 mg (90% or more) of ethyl esters of n-3 fatty acids or placebo daily and to receive either insulin glargine or standard care. The primary outcome was death from cardiovascular causes. The results of the comparison between n-3 fatty acids and placebo are reported here.
Results During a median follow up of 6.2 years, the incidence of the primary outcome was not significantly decreased among patients receiving n-3 fatty acids, as compared with those receiving placebo (574 patients [9.1%] vs. 581 patients [9.3%]; hazard ratio, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72). The use of n-3 fatty acids also had no significant effect on the rates of major vascular events (1034 patients [16.5%] vs. 1017 patients [16.3%]; hazard ratio, 1.01; 95% CI, 0.93 to 1.10; P=0.81), death from any cause (951 [15.1%] vs. 964 [15.4%]; hazard ratio, 0.98; 95% CI, 0.89 to 1.07; P=0.63), or death from arrhythmia (288 [4.6%] vs. 259 [4.1%]; hazard ratio, 1.10; 95% CI, 0.93 to 1.30; P=0.26). Triglyceride levels were reduced by 14.5 mg per deciliter (0.16 mmol per liter) more among patients receiving n-3 fatty acids than among those receiving placebo (P<0.001), without a significant effect on other lipids. Adverse effects were similar in the two groups.
Conclusions Daily supplementation with 1 g of n-3 fatty acids did not reduce the rate of cardiovascular events in patients at high risk for cardiovascular events.
See following website for full manuscript.
• The totality of the publicly available scientific evidence demonstrates a cardiovascular benefit of EPA and DHA in healthy populations, as well as in the majority of populations with pre-existing cardiovascular ailments.
• The list of long-chain omega-3 recommendations from professional organizations and government bodies continues to grow because the cardiovascular benefits associated with EPA and DHA are so compelling.
What Else Should You Know?
• Subgroup analyses in previous studies have demonstrated cardiovascular (CV) benefits in diabetic subjects.
• Compared to past studies demonstrating CV benefits of the long-chain O-3s, subjects in the current trial received better treatment with statins, antithrombotics and antihypertensive medications. Such treatment makes it less likely to be able to detect a benefit of the long-chain O-3s.
• The current trial may not have been adequately powered to detect differences between the treatment and placebo groups.
• Results from the present study cannot be generalized to the general “healthy” population because of the unique subject characteristics.
• All Subjects had impaired fasting glucose, impaired glucose tolerance or diabetes, all of which are considered risk factors for CV events. Half of the subjects received the insulin analogue glargine. It is unknown what effect, if any, the CV risk factors and the glargine have on the beneficial effects of O-3s.
• O-3 blood levels were not reported.
• 840 mg EPA + DHA may have been too low a dose to demonstrate any significant CV benefit(s).
• The supplementation period may have been too short to demonstrate any significant CV benefit(s).
• While there was a significant reduction in triglycerides in the O-3 supplemented group compared to the placebo group, corroborating O-3's ability to lower triglycerides, it is curious that there were no other significant between-group differences in the levels of other lipid fractions, plasma glucose levels, glycated hemoglobin levels, blood pressure, or heart rate.
• It has been estimated that low O-3 PUFA intakes account for 72,000-96,000 deaths per year from CVD in the United States alone (Danaei et al., 2009).
Global Organization for EPA and DHA Omega-3s (2012). Omega-3s & Cardiovascular Outcomes in Individuals with Dysglycemia [Peer commentary on the paper “N-3 fatty acids and cardiovascular outcomes in patients with dysglycemia” by Origin Trial Investigators Gerstein H Yusuf S Rydén L Bosch J Richardson L Dagenais G Diaz R, Johnston P Maggioni A Probstfield J Ramachandran A Riddle M and Vige R (published online June 11, 2012). N Engl J Med. Doi: 10.1056/NEJMoa1203859.].
Danaei G Ding EL Mozaffarian D Taylor B Rehm J Murray CJ and Ezzati M (2009). The preventable causes of death in the United States: Comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med 6: e1000058.