Adding omega-3 fatty acids to stable statin therapy reduces triglyceride levels, without raising LDL

October 08, 2007

New York, NY - The addition of an omega-3 fatty-acid supplement to statin therapy in patients with persistent hypertriglyceridemia significantly reduced triglyceride levels and non-HDL-cholesterol levels, all without a significant increase in LDL-cholesterol levels[1].

"We often see clinical situations with our patients where they are being treated with a statin but continue to have elevations in triglyceride levels," lead investigator Dr Harold Bays (Louisville Metabolic and Atherosclerosis Research Center, KY) told heart wire . "The purpose of this study was to determine the lipid effects when we add on a prescription omega-3 formulation to patients already on stable statin therapy."

Presenting the results of the study at the 16th International Symposium on Drugs Affecting Lipid Metabolism in New York City this weekend, Bays explained that while the Food and Drug Administration has approved the addition of omega-3 fatty-acid supplementation to statin-treated patients with triglyceride levels >500 mg/dL, the addition of the polyunsaturated fatty acid is not currently approved for use in patients with triglyceride levels <500 mg/dL.

Testing the lipid effects of adding omega-3 fatty acids to statin-treated patients with triglyceride levels >200 mg/dL but <500 mg/dL, investigators randomized 254 patients treated with simvastatin 40 mg for eight weeks or more to 4 g/day of prescription omega-3 fatty acid (Lovaza, Reliant Pharmaceuticals) or placebo.

After eight weeks of treatment, patients who received the omega-3 fatty-acid prescription had a 29.5% decrease in triglyceride levels compared with a 6.3% reduction among those randomized to placebo. There was also a significant 9.0% reduction in non-HDL cholesterol among those treated with the fatty acid compared with a 2.2% reduction in the placebo-treatment arm. There was a median increase in LDL cholesterol among those treated with omega-3 fatty acids, about 0.7%, but this was not significant compared with placebo.

Changes in lipid parameters (median)

Lipid parameter Simvastatin 40 mg and omega-3 fatty acid (baseline), mg/dL Simvastatin 40 mg and omega-3 fatty acid (final), mg/dL Simvastatin 40 mg and placebo (baseline), mg/dL Simvastatin 40 mg and placebo (final), mg/dL p (change between groups)
Non-HDL cholesterol 137.0 122.8 141.3 133.5 <0.001
Triglycerides 267.8 182.3 270.7 259.5 <0.001
LDL cholesterol 90.7 87.5 88.2 85.0 <0.001
VLDL cholesterol 51.5 36.5 52.0 48.5 <0.001

"What is most applicable to physicians is that there was an approximate 30% reduction in triglyceride levels among those treated with the omega-3 fatty acids," said Bays. "When we look at the LDL-cholesterol levels, there was no significant difference in the change in LDL cholesterol in this trial. There was a small median increase, which wasn't significant. The reason this is important is because we can now say that many patients who have persistent elevations in their triglyceride levels, even after they've been on stable statin therapy, can benefit from dietary supplementation. Adding the omega-3 fatty acid can lower triglycerides and lower non-HDL cholesterol, all without adversely affecting LDL levels."

Bays told heartwire that the omega-3 fatty acid, when added to simvastatin, increased mean LDL-particle size compared with placebo and that this improvement in LDL-particle size was directly related to end-of-treatment triglyceride levels. He suspects that an improvement in LDL-particle size may not occur unless a certain "threshold" triglyceride level is reached, somewhere around 100 to 200 mg/dL.

Bays acknowledged that the study addresses only the reduction in triglyceride levels and that it is not clear what clinical benefit would arise from further lowering triglycerides in patients with levels between 200 mg/dL and 500 mg/dL.

The main outcome measure of this study, percent change in non-HDL cholesterol from baseline to the end of treatment, was published earlier this year in Clinical Therapeutics[2].

Reliant Pharmaceuticals sponsored the study. Bays reports receiving research grants as well as well consulting and/or speaker fees from Reliant Pharmaceuticals, AstraZeneca, Abbott, Boehringer Ingelheim, Eli Lilly, Kos, Merck, and Pfizer, among others.

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