Long-Term Comparison of Ethyl Icosapentate vs. Omega-3-Acid Ethyl in Patients With Cardiovascular Disease and Hypertriglyceridemia (DEFAT Trial)

BACKGROUND: Numerous studies have demonstrated a reduction in cardiovascular events when the low-density lipoprotein cholesterol (LDL) level is decreased by statin therapy. However, despite good control of LDL, cardiovascular events may increase if the triglyceride (TG) level is high. We conducted a long-term comparison of treatment of hypertriglyceridemia with ethyl icosapentate (EPA) vs. omega-3-acid ethyl (EPA+docosahexaenoic acid [DHA]). METHODS AND RESULTS: Cardiac surgery patients with hypertriglyceridemia were randomized to an EPA group (1.8 g t.i.d.) or an EPA+DHA group (2 g s.i.d.) and observed for 3 years. The primary endpoints were the serum TG level and its percent change. Secondary endpoints included lipid markers, fatty acid parameters, serum creatinine, cystatin-C, oxidized LDL, high-sensitivity C-reactive protein, and MACCE. An interview to assess study drug adherence was conducted 6 months after completing the study. TG levels were significantly lower in the EPA+DHA group than in the EPA group. Levels of remnant-like particles-cholesterol, oxidized LDL, and cystatin-C were also significantly lower in the EPA+DHA group than in the EPA group. Compliance with treatment was significantly worse in the EPA group. CONCLUSIONS: Better results were obtained in the EPA+DHA group, but more patients showed poor compliance with treatment in the EPA group, making detailed comparison of the 2 groups difficult. Even so, TG were reduced while EPA and DHA levels were increased in the EPA+DHA group, together with a reduction in oxidative stress and remnant-like particles-cholesterol. Decreased compliance with medication in the EPA group significantly affected the results of this study, clearly indicating the importance of good compliance.