Effects of prescription omega-3-acid ethyl esters on non--high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin

Abstract

Objective: To evaluate the effects of prescription omega-3-acid ethyl esters on non-high-density lipoprotein cholesterol (HDL-C) levels in atorvastatin-treated patients with elevated non-HDL-C and triglyceride levels.

Patients and methods: This study, conducted between February 15, 2007, and October 22, 2007, randomized patients with elevated non-HDL-C (>160 mg/dL) and triglyceride (>or=250 mg/dL and <or=599 mg/dL) levels to double-blind treatment with prescription omega-3-acid ethyl esters, 4 g/d, or placebo for 16 weeks. Patients also received escalating dosages of open-label atorvastatin (weeks 0-8, 10 mg/d; weeks 9-12, 20 mg/d; weeks 13-16, 40 mg/d).

Results: Prescription omega-3-acid ethyl esters plus atorvastatin, 10, 20, and 40 mg/d, reduced median non-HDL-C levels by 40.2% vs 33.7% (P<.001), 46.9% vs 39.0% (P<.001), and 50.4% vs 46.3% (P<.001) compared with placebo plus the same doses of atorvastatin at the end of 8, 12, and 16 weeks, respectively. Prescription omega-3-acid ethyl esters plus atorvastatin also reduced median total cholesterol, triglyceride, and very low-density lipoprotein cholesterol levels and increased HDL-C levels to a significantly greater extent than placebo plus atorvastatin. Percent changes from baseline low-density lipoprotein-cholesterol, apolipoprotein A-I, and apolipoprotein B levels were not significantly different between groups at the end of the study.

Conclusion: Prescription omega-3-acid ethyl esters plus atorvastatin produced significant improvements in non-HDL-C and other lipid parameters in patients with elevated non-HDL-C and triglyceride levels.

Trial registration: ClinicalTrials.gov NCT00435045.

FIGURE 1.

Flow of patients through the trial. P-OM3 = prescription omega-3-acid ethyl esters.

FIGURE 2.

Median change from baseline in non—high-density lipoprotein cholesterol (HDL-C) levels (modified intention-to-treat population). Error bars represent interquartile ranges. The difference between medians was −6.5% (90% confidence interval [CI], −7.2% to −2.9%; P<.001) at week 8, −7.9% (90% CI, −9.1% to −4.9%; P<.001) at week 12, and −4.1% (90% CI, −6.8% to −2.4%; P<.001) at week 16. P-OM3 = prescription omega-3-acid ethyl esters.

FIGURE 3.

Difference in median change from baseline in lipoprotein lipid parameters between prescription omega-3-acid ethyl esters (P-OM3) and placebo, when given in combination with atorvastatin, 10, 20, and 40 mg/d. P values are calculated for the difference in the median percentage change from baseline between P-OM3 and placebo. P values were <.001 for total cholesterol (TC); <.001 for high-density lipoprotein cholesterol (HDL-C); 0.24, 0.86, and 0.64 for low-density lipoprotein cholesterol (LDL-C) during the 10-mg, 20-mg, and 40-mg phases, respectively; and <.001 for very low-density lipoprotein cholesterol (VLDL-C) and triglycerides (TG).