Lipid Effects of Icosapent Ethyl in Women with Diabetes Mellitus and Persistent High Triglycerides on Statin Treatment: ANCHOR Trial Subanalysis

Abstract

Background: High triglycerides (TG) and diabetes mellitus type 2 (DM2) are stronger predictors of cardiovascular disease (CVD) in women than in men, but few randomized, controlled clinical trials have investigated lipid-lowering interventions in women and none have reported results specifically in women with high TG and DM2. Icosapent ethyl (Vascepa) is pure prescription eicosapentaenoic acid (EPA) ethyl ester approved at 4 g/day as an adjunct to diet to reduce TG ≥500 mg/dL.

Methods: The 12-week ANCHOR trial randomized 702 statin-treated patients (73% with DM; 39% women) at increased CVD risk with TG 200-499 mg/dL despite controlled low-density lipoprotein cholesterol (LDL-C; 40-99 mg/dL) to receive icosapent ethyl 2 g/day, 4 g/day, or placebo. This post hoc analysis included 146 women with DM2 (97% white, mean age 62 years) randomized to icosapent ethyl 4 g/day (n = 74) or placebo (n = 72).

Results: Icosapent ethyl significantly reduced TG (-21.5%; p < 0.0001) without increasing LDL-C and lowered other potentially atherogenic lipid/lipoprotein, apolipoprotein, and inflammatory parameters versus placebo. Icosapent ethyl increased EPA levels in plasma (+639%; p < 0.0001; n = 49) and red blood cells (+599%; p < 0.0001; n = 47) versus placebo. Safety and tolerability of icosapent ethyl were generally similar to placebo.

Conclusion: In women with DM2 at high CVD risk with persistently high TG on statins, icosapent ethyl 4 g/day reduced potentially atherogenic parameters with safety and tolerability comparable to placebo. Potential CVD benefits of icosapent ethyl are being tested in ∼8000 men and women at high CVD risk with high TG on statins in the ongoing Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial (REDUCE-IT) cardiovascular (CV) outcome trial.

Keywords: cardiovascular diseases; diabetes mellitus; eicosapentaenoic acid; hypertriglyceridemia; women's health.

Conflict of interest statement

Dr. Brinton serves as a consultant and/or speaker (including receipt of honoraria) for Aegerion, Akcea, Alexion, Amarin, Boehringer Ingelheim, Janssen, Kowa, Merck, Novo-Nordisk, Sanofi, and Regeneron. Dr. Ballantyne has received research/grant support from Amarin Pharma, Inc., Amgen, Eli Lilly, Esperion, Ionis, Novartis Pharmaceuticals Corp., Pfizer, Regeneron, Roche Diagnostic, Sanofi-Synthelabo, National Institutes of Health, American Diabetes Association, and American Heart Association (all paid to institution, not individual) and is a consultant for Amarin Pharma, Inc., Amgen, AstraZeneca, Eli Lilly, Esperion, Genzyme, Matinas BioPharma, Merck & Co., Novartis Pharmaceuticals Corp., Pfizer, Regeneron, Roche Diagnostics, and Sanofi-Synthelabo. Dr. Guyton has received research/grant support from Amarin Pharma, Inc., Amgen, Regeneron, and Sanofi and has provided advisory services for Amgen and the FH Foundation. Dr. Philip, Mr. Doyle, and Dr. Juliano are employees and stock shareholders of Amarin Pharma, Inc. Dr. Mosca has provided consultancy services for Amarin Pharma, Inc., Aralez, and CocoaVia.

Figures

FIG. 1.

Percent change in atherosclerosis risk parameters with icosapent ethyl 4 g/day in women with DM2 from the ANCHOR trial. Values represent median difference in percent change from baseline for icosapent ethyl 4 g/day versus placebo. *p < 0.0001; †p < 0.001; ‡p < 0.05; NS, not significant versus placebo. Apo C-III, apolipoprotein C-III; Apo B, apolipoprotein B; DM, diabetes mellitus; non-HDL-C, non-high-density lipoprotein cholesterol; hsCRP, high-sensitivity C-reactive protein; LDL-C, low-density lipoprotein cholesterol; ox-LDL, oxidized low-density lipoprotein; RLP-C, remnant lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; VLDL-C, very-low-density lipoprotein cholesterol; VLDL-TG, very-low-density lipoprotein triglycerides.