Diabetes Metab J.  2020 Feb;44(1):78-90. 10.4093/dmj.2018.0265.

Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

• Jun JE
• Jeong IK
• Yu JM
• Kim SR
• Lee IK
• Han KA
• Choi SH
• Kim SK
• Park HK
• Mok JO
• Lee YH
• Kwon HS
• Kim SH
• Kang HC
• Lee SA
• Lee CB
• Choi KM
• Her SH
• Shin WY
• Shin MS
• Ahn HS
• Kang SH
• Cho JM
• Jo SH
• Cha TJ
• Kim SY
• Won KH
• Kim DB
• Lee JH
• Lee MK

• KMID: 2470957
• DOI: http://doi.org/10.4093/dmj.2018.0265

Abstract

BACKGROUND
Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia.
METHODS
This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment.
RESULTS
After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups.
CONCLUSION
The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

Keyword

Atorvastatin; Fatty acids, omega-3; Hypertriglyceridemia

MeSH Terms

Adult
Atorvastatin Calcium
Cholesterol
Cholesterol, LDL
Dyslipidemias
Fasting
Fatty Acids, Omega-3*
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors*
Hypertriglyceridemia*
Incidence
Lipoproteins
Triglycerides
Atorvastatin Calcium
Cholesterol
Cholesterol, LDL
Fatty Acids, Omega-3
Lipoproteins

Figure

• 

  Fig. 1 Study design. Adult subjects with high cardiovascular disease risk were screened, and eligible subjects underwent a 4-week run-in period of open label atorvastatin 20 mg/day, and were scheduled for a second screening. Enrolled subjects were randomly assigned in a 1:1 ratio to each of the two groups (ATOMEGA group or atorvastatin group) for 8 weeks of treatment. Individuals in ATOMEGA group were prescribed four capsules of ATOMEGA containing omega-3 fatty acids 1,000 mg plus atorvastatin calcium 5 mg and one tablet of placebo of atorvastatin 20 mg/day. Individuals in the atorvastatin group were prescribed four capsules of placebo (olive oil 1,000 mg) and one tablet of atorvastatin calcium 20 mg.

• 

  Fig. 2 Percent change in lipid parameters from baseline after 8 weeks of treatment. Black bar represents the change in lipid parameters in the ATOMEGA group, while white vertical rectangle represents the change in lipid parameters in the atorvastatin group. TG, triglyceride; HDL-C, high density lipoprotein cholesterol; TC, total cholesterol; LDL-C, low density lipoprotein cholesterol; VLDL-C, very low density lipoprotein cholesterol; Apo A, apolipoprotein A; Apo B, apolipoprotein B. aP<0.05, bP<0.001 for the difference between ATOMEGA and atorvastatin group.

• 

  Fig. 3 Comparison of triglyceride (TG) and non-high density lipoprotein cholesterol (non-HDL-C) lowering efficacy between ATOMEGA group (black bar) and atorvastatin group (white bar) in various subgroups. BMI, body mass index; eGFR, estimated glomerular filtration rate; CHD, coronary heart disease. aP<0.05, bP<0.01, cP<0.001 for the difference between the two groups.

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