Efficacy and Safety of Eicosapentaenoic Acid Ethyl Ester (AMR101) Therapy in Statin-Treated Patients With Persistent High Triglycerides (From the ANCHOR Study)

Study Questions:

Does AMR101, an ω-3 fatty acid agent, lower triglycerides (TGs) among statin-treated patients with persistent high TGs?

Methods:

This was a phase 3, multicenter, placebo-controlled, randomized, double-blinded trial, which examined the effects of AMR101 (an ω-3 fatty acid agent containing >96% pure icosapent-ethyl, the ethyl ester of eicosapentaenoic acid) on TG levels. Participants were defined as high-risk statin-treated patients with residually high TG levels (>200 and <500 mg/dl) despite low-density lipoprotein (LDL) cholesterol control (>40 and <100 mg/dl). Participants on a stable diet were randomized to AMR101 4 or 2 g/day or placebo. The primary endpoint was median percent change in TG levels from baseline versus placebo at 12 weeks. Additional endpoints included safety outcomes.

Results:

A total of 702 participants were included in this clinical trial, of which 663 completed the trial (>90% in each treatment group). Median LDL cholesterol level was 83.0 mg/dl, and 21% of patients had baseline LDL cholesterol levels <70 mg/dl. Most patients (93.2%) were taking medium- or high-efficacy statin regimens, and 90.2% were on statin therapy before screening. Median baseline TG level was 259.0 mg/dl. Participants with diabetes had a mean baseline glycated hemoglobin <7% and fasting plasma glucose <136 mg/dl for all groups. AMR101 4 and 2 g/day significantly decreased TG levels by 21.5% (p < 0.0001) and 10.1% (p = 0.0005), respectively, and non-high-density lipoprotein (non-HDL) cholesterol by 13.6% (p < 0.0001) and 5.5% (p = 0.0054), respectively. AMR101 4 g/day produced greater TG and non-HDL cholesterol decreases in patients with higher-efficacy statin regimens, and greater TG decreases in patients with higher baseline TG levels. AMR101 4 g/day decreased LDL cholesterol by 6.2% (p = 0.0067) and decreased apolipoprotein B (9.3%), total cholesterol (12.0%), very-LDL cholesterol (24.4%), lipoprotein-associated phospholipase A2 (19.0%), and high-sensitivity C-reactive protein (22.0%) versus placebo (p < 0.001 for all comparisons). AMR101 was generally well tolerated, with safety profiles similar to placebo.

Conclusions:

The investigators concluded that AMR101 4 g/day significantly decreased median placebo-adjusted TG, non-HDL cholesterol, LDL cholesterol, apolipoprotein B, total cholesterol, very-LDL cholesterol, lipoprotein-associated phospholipase A2, and high-sensitivity C-reactive protein in statin-treated patients with residual TG elevations.

Perspective:

These data suggest a significant improvement in TG levels among patients taking statins, particularly for the 4 g dose. However, as the investigators point out, further research is warranted, including data on cardiovascular outcomes.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Diet

Keywords: Hypertriglyceridemia, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Eicosapentaenoic Acid, Glucose, Cholesterol, United States Food and Drug Administration, Fatty Acids, Omega-3, Cardiovascular Diseases, Diet, Triglycerides, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Diabetes Mellitus, Fasting


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