In patients at high risk for cardiovascular events and have impaired fasting glucose, impaired glucose tolerance, or diabetes, what are the benefits (death from cardiovascular causes) and risks (adverse effects) of 1-g n-3 fatty acids (containing at least 900mg of ethyl esters) compared to placebo at 6.2 years of therapy?
Answer
Efficacy Outcomes
In 12,536 patients (n=6281 in n-3 fatty acid group and n=6255 in placebo group), there was no statistical difference in the primary outcome of death from cardiovascular causes after a median follow-up of 6.2 years. All secondary outcomes (mycoardial infarction, stroke, death from cardiovascular causes, death from any cause/arrhythmia, hospitalization for heart failure, revascularization procedure, angina, limb or digit amputation for ischemia, and hospitalization for any cardiovascular cause) were all non-significant. By the end of the trial, patients in the group receiving n-3 fatty acids had a mean reduction in the triglyceride level of 0.16mmol/L as compared to placebo (p<0.001). No significant between-group differences in the levels of other lipid fractions, plasma glucose levels, glycated hemoglobin levels, blood pressure, or heart rate.
Adverse Effects
The most commonly reported reasons for permanently stopping a study drug was abdominal discomfort (n=32 (0.51%) in the n-3 fatty acid group and 18 (0.29%) in the placebo group), lower gastrointestinal symptoms (n=14 in n-3 fatty acid group and 24 in the placebo group). Bleeding was reported in 57 (0.91%) patients receiving n-3 fatty acids, as compared with 65 (1.04%) patients in the placebo group, with intracranial bleeding reported in 42 patients, and 51 patients, respectively.
Reference: The ORIGIN Trial Investigators. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med 2012.published on June 11, 2012.
