A Head-to-Head Comparison of a Free Fatty Acid Formulation of Omega-3 Pentaenoic Acids Versus Icosapent Ethyl in Adults With Hypertriglyceridemia: The ENHANCE-IT Study.

Content Provider	Europe PMC
Author	Maki, Kevin C. Bays, Harold E. Ballantyne, Christie M. Underberg, James A. Kastelein, John J. P. Johnson, Judith B. Ferguson, James J. Bays, Harold Blomer, Allison Kelley, Kathleen Patel, Alpa Scott, John K Surowitz, Ronald Z Toth, Philip D Trivedi, Rupal
Abstract	BackgroundMAT9001 is an omega‐3 free fatty acid (FFA) formulation containing mainly eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA). Compared with icosapent ethyl (EPA‐ethyl esters [EE]), EPA+DPA‐FFA previously showed enhanced triglyceride lowering and higher plasma EPA when both were administered once daily with a very–low fat diet. This trial compared pharmacodynamic responses and plasma omega‐3 levels following twice daily dosing, with meals, of EPA+DPA‐FFA and EPA‐EE in hypertriglyceridemic subjects consuming a Therapeutic Lifestyle Changes diet.Methods and ResultsThis open‐label, randomized, 2‐way crossover trial, with 28‐day treatment periods separated by ≥28‐day washout, was conducted at 8 US centers and included 100 subjects with fasting triglycerides 1.70 to 5.64 mmol/L (150–499 mg/dL) (median 2.31 mmol/L [204 mg/dL]; 57% women, average age 60.3 years). The primary end point was least squares geometric mean percent change from baseline plasma triglycerides. In the 94 subjects with analyzable data for both treatment periods, EPA+DPA‐FFA and EPA‐EE reduced least squares geometric mean triglycerides from baseline: 20.9% and 18.3%, respectively (P=not significant). EPA+DPA‐FFA reduced least squares geometric mean high‐sensitivity C‐reactive protein by 5.8%; EPA‐EE increased high‐sensitivity C‐reactive protein by 8.5% (P=0.034). EPA+DPA‐FFA increased least squares geometric mean plasma EPA, DPA, and total omega‐3 (EPA+docosahexaenoic acid+DPA) concentrations by 848%, 177%, and 205%, respectively, compared with corresponding changes with EPA‐EE of 692%, 140%, and 165% (all P<0.001). EPA+DPA‐FFA increased docosahexaenoic acid by 1.7%; EPA‐EE decreased docosahexaenoic acid by 3.3% (P=0.011). Lipoprotein cholesterol and apolipoprotein responses did not differ between treatments.ConclusionsEPA+DPA‐FFA raised plasma EPA, DPA, and total omega‐3 significantly more than did EPA‐EE. EPA+DPA‐FFA also reduced triglycerides and high‐sensitivity C‐reactive protein without increasing low‐density lipoprotein cholesterol.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT04177680.
Page Count	21
Journal	Journal of the American Heart Association
Volume Number	11
PubMed Central reference number	PMC9075326
Issue Number	6
PubMed reference number	35232215
e-ISSN	20479980
DOI	10.1161/jaha.121.024176
Language	English
Publisher	John Wiley and Sons Inc.
Publisher Date	2022-03-01
Publisher Place	Hoboken
Access Restriction	Open
Rights License	This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. © 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Subject Keyword	docosapentaenoic acid eicosapentaenoic acid hypertriglyceridemia omega‐3 fatty acids triglycerides Primary Prevention Cardiovascular Disease Lipids and Cholesterol
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine