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

Clin Ther. 2021 Aug;43(8):1419-1430. doi: 10.1016/j.clinthera.2021.07.001. Epub 2021 Jul 29.

Abstract

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/Ω-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/Ω-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/Ω-3 fatty acid was associated with a greater reduction of triglyceride and non-HDL-C compared with atorvastatin + placebo, without significant adverse events.

Keywords: atorvastatin; combination treatment; hypertriglyceridemia; non–HDL-C; Ω-3 fatty acid.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atorvastatin / adverse effects
  • Double-Blind Method
  • Fatty Acids, Omega-3*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Hypertriglyceridemia* / drug therapy
  • Pyrroles
  • Treatment Outcome
  • Triglycerides

Substances

  • Fatty Acids, Omega-3
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Triglycerides
  • Atorvastatin