Effects of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) on Atherogenic Lipid/Lipoprotein, Apolipoprotein, and Inflammatory Parameters in Patients With Elevated High-Sensitivity C-Reactive Protein (from the ANCHOR Study)

• Published in: The American journal of cardiology Vol. 124; no. 5; pp. 696 - 701
• Main Authors: Miller, Michael, Ballantyne, Christie M., Bays, Harold E., Granowitz, Craig, Doyle, Ralph T., Juliano, Rebecca A., Philip, Sephy
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2019; Elsevier Limited
• Subjects: Adult; Aged; Apolipoprotein B; Apolipoprotein C-III; Apolipoprotein C-III - blood; Apolipoproteins; Atherosclerosis - diagnosis; Atherosclerosis - drug therapy; C-reactive protein; C-Reactive Protein - metabolism; Cardiovascular disease; Cardiovascular diseases; Cell adhesion; Cholesterol; Cholesterol, LDL - blood; Coronary vessels; Density; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug dosages; Drug Substitution - methods; Eicosapentaenoic acid; Eicosapentaenoic Acid - analogs & derivatives; Eicosapentaenoic Acid - therapeutic use; Erythrocytes; FDA approval; Female; Health risks; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypertriglyceridemia - blood; Hypertriglyceridemia - diagnosis; Hypertriglyceridemia - drug therapy; Hypolipidemic Agents - therapeutic use; Inflammation; Intercellular adhesion molecule 1; Interleukin 6; Interleukins; Lipids; Lipoproteins; Low density lipoprotein; Male; Middle Aged; Parameter sensitivity; Phospholipase; Phospholipase A2; Population; Prognosis; Proteins; Randomization; Risk Assessment; Sensitivity; Severity of Illness Index; Statins; Treatment Outcome; Triglycerides; United States; United States; United States > US
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2019.05.057

Icosapent ethyl is pure prescription eicosapentaenoic acid approved at 4 g/day as an adjunct to diet to reduce triglycerides (TG) in adults with TG ≥500 mg/dl. Elevated high-sensitivity C-reactive protein (hsCRP) is associated with increased cardiovascular risk. The 12-week ANCHOR study randomized 702 statin-treated patients at increased cardiovascular risk with TG 200 to 499 mg/dl despite low-density lipoprotein cholesterol (LDL-C) control (40 to 99 mg/dl). This post hoc analysis assessed 246 ANCHOR patients with baseline hsCRP ≥ 2.0 mg/L randomized to icosapent ethyl 4 g/day (n = 126; approved dose) or placebo (n = 120). Without increasing LDL-C, icosapent ethyl significantly reduced median TG (−20%; p < 0.0001), non–high-density lipoprotein cholesterol (−12.3%; p < 0.0001), total cholesterol (−11.1%; p < 0.0001), high-density lipoprotein cholesterol (−5.2%; p = 0.0042), very LDL-C (−21.0%; p < 0.0001), very low-density lipoprotein TG (−22.9%; p < 0.0001), remnant lipoprotein cholesterol (−23.0%; p = 0.0125), apolipoprotein B (−7.4%; p = 0.0021), apolipoprotein C-III (−16%; p < 0.0001), oxidized LDL (−13.7%; p = 0.0020), lipoprotein-associated phospholipase A2 (−19.6%; p < 0.0001), and hsCRP (−17.9%; p = 0.0213) versus placebo, while interleukin-6 and intercellular adhesion molecule-1 were not significantly changed. Eicosapentaenoic acid increased with icosapent ethyl 4 g/day +637% in plasma and +632% in red blood cells versus placebo (both p < 0.0001). Icosapent ethyl exhibited a safety profile similar to placebo. In conclusion, in statin-treated patients with hsCRP ≥ 2.0 mg/L and TG 200 to 499 mg/dl at baseline, icosapent ethyl 4 g/day significantly and safely reduced TG and other atherogenic and inflammatory parameters without increasing LDL-C versus placebo.