Comparison of the Efficacy and Safety of Atorvastatin 40 mg/ω-3 Fatty Acids 4 g Fixed-dose Combination and Atorvastatin 40 mg Monotherapy in Hypertriglyceridemic Patients who Poorly Respond to Atorvastatin 40 mg Monotherapy: An 8-week, Multicenter, Randomized, Double-blind Phase III Study

Purpose: Residual cardiovascular risk in patients with hypertriglyceridemia, despite optimal low-density lipoprotein cholesterol levels being achieved with intensive statin treatment, is a global health issue. The purpose of this study was to investigate the efficacy and tolerability of treatment with a combination of high-dose atorvastatin/Q-3 fatty acid Purpose: Residual cardiovascular risk in patients with hypertriglyceridemia, despite optimal low-density lipoprotein cholesterol levels being achieved with intensive statin treatment, is a global health issue. The purpose of this study was to investigate the efficacy and tolerability of treatment with a combination of high-dose atorvastatin/Q-3 fatty acid compared to atorvastatin + placebo in patients with hypertriglyceridemia who did not respond to statin treatment. Methods: In this multicenter, randomized, double-blind, placebo-controlled study, patients who had residual hypertriglyceridemia after a 4-week run-in period of atorvastatin treatment were randomly assigned to receive UI-018 (fixed-dose combination atorvastatin/Q-3 fatty acid 40 mg/4 g) or atorvastatin 40 mg + placebo (control). The primary efficacy end points were the percentage change from baseline in non-high density lipoprotein cholesterol (non-HDL-C) level at the end of treatment and the adverse events recorded during treatment. A secondary end point was the percentage change from baseline in triglyceride level. Findings: After 8 weeks of treatment, the percentage changes from baseline in non-HDL-C (-4.4% vs + 0.6%; p = 0.02) and triglycerides (-18.5% vs + 0.9%; p < 0.01) were significantly greater in the UI-018 group ( n = 101) than in the control group ( n = 99). These changes were present in subgroups of advanced age ( >65 years), status (body mass index >25 kg/m2), or without diabetes. The prevalences of adverse events did not differ between the 2 treatment groups. Implications: In patients with residual hypertriglyceridemia despite receiving statin treatment, a combination of high-dose atorvastatin/Q-3 fatty acid was associated with a greater reduction of triglyceride and non-HDL-C compared with atorvastatin + placebo, without significant adverse events. (Clin Ther. 2021;43:1419-1430.) (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)