Elsevier

Mayo Clinic Proceedings

Volume 85, Issue 2, February 2010, Pages 122-128
Mayo Clinic Proceedings

ORIGINAL ARTICLE
Effects of Prescription Omega-3-Acid Ethyl Esters on Non—High-Density Lipoprotein Cholesterol When Coadministered With Escalating Doses of Atorvastatin

https://doi.org/10.4065/mcp.2009.0397Get rights and content

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 (≥250 mg/dL and ≤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.

Section snippets

PATIENTS AND METHODS

Men and women were eligible to participate in the study if they were between the ages of 18 and 79 years, medically stable, and, in the judgment of the investigators, otherwise acceptable for entry on the basis of the findings of medical history, physical examination, electrocardiography, and routine laboratory tests. Lipid entry criteria required a non—HDL-C level greater than 160 mg/dL and a triglyceride level between 250 and 599 mg/dL at the end of a diet lead-in period. Women of

RESULTS

A total of 585 patients were screened for eligibility, with 245 patients (41.9%) being randomized (123 to P-OM3 plus atorvastatin and 122 to placebo plus atorvastatin) and 219 (89.4%) completing 16 weeks of study treatment. Disposition of patients is shown in Figure 1. Baseline characteristics of randomized patients (Table 1) revealed no statistically significant differences between the 2 groups. The mean age of study participants was 56 years, and most randomized patients were men (142/245

DISCUSSION

In this study, coadministration of P-OM3, 4 g/d, with atorvastatin, 10 to 40 mg/d, lowered non—HDL-C levels to a significantly greater extent than the same dose of atorvastatin alone in patients with elevated triglyceride and non—HDL-C levels. The effects of adding P-OM3 to either 10 or 20 mg/d of atorvastatin were comparable to that of doubling the atorvastatin dose in lowering non—HDL-C levels.

Combining P-OM3, 4 g/d, with atorvastatin also reduced median TC, triglyceride, and VLDL-C levels

CONCLUSION

Coadministration of P-OM3 with 10 to 40 mg of atorvastatin significantly reduced non—HDL-C levels compared to the same dose of atorvastatin alone in patients with elevated non—HDL-C and triglyceride levels. In addition, P-OM3 improved other lipid parameters. Generally, P-OM3 added to atorvastatin was well tolerated at all atorvastatin doses. Coadministration of P-OM3 with statin therapy may be a rational treatment approach for improving non—HDL-C levels and other lipid parameters in patients

Acknowledgments

We acknowledge the following individuals for their contributions to the draft development and critical review of the submitted manuscript: Rose Snipes, MD; Amy Meadowcroft, PharmD; Rosemary Schroyer, MS; and Doug Wicks, MPH.

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    Portions of this manuscript have been presented in abstract and poster presentations.1, 2, 3

    Manuscript writing and editing support by Kevin Jarvis, PharmD, from BioCentric, inc, was funded by GlaxoSmithKline. Funding for this study was provided by GlaxoSmithKline, Research Triangle Park, NC (NCT00435045).

    Dr Bays and Dr Maki have served as clinical investigators, received research grants, and received consultant, adviser, and speaker fees from numerous pharmaceutical companies, including Reliant and GlaxoSmithKline. Mr Doyle is a former employee of Reliant Pharmaceuticals and has received consultant fees from GlaxoSmithKline. Dr Carter is currently the CEO of WellGen Inc. Dr McKenney serves as a consultant for Abbott Laboratories, Agerion, AstraZeneca, GlaxoSmithKline, Merck & Co, and Daiichi Sankyo. Dr Stein has received consulting fees, honorarium, or research funding for specific clinical trials from GlaxoSmithKline, Reliant Pharmaceuticals, Merck & Co, Schering Plough, Daiichi Sankyo, AstraZeneca, Abbott, ISIS, Genzyme, and Food and Drug Administration.

    This article is freely available on publication, because the authors have chosen the immediate access option.

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