Efficacy and Safety of Adding Omega-3 Fatty Acids in Statin-treated Patients with Residual Hypertriglyceridemia: ROMANTIC (Rosuvastatin-OMAcor iN residual hyperTrIglyCeridemia), a Randomized, Double-blind, and Placebo-controlled Trial

Clin Ther. 2018 Jan;40(1):83-94. doi: 10.1016/j.clinthera.2017.11.007. Epub 2017 Dec 7.


Purpose: The purpose of this study was to examine the efficacy and safety of adding ω-3 fatty acids to rosuvastatin in patients with residual hypertriglyceridemia despite statin treatment.

Methods: This study was a multicenter, randomized, double-blind, placebo-controlled study. After a 4-week run-in period of rosuvastatin treatment, the patients who had residual hypertriglyceridemia were randomized to receive rosuvastatin 20 mg/d plus ω-3 fatty acids 4 g/d (ROSUMEGA group) or rosuvastatin 20 mg/d (rosuvastatin group) with a 1:1 ratio and were prescribed each medication for 8 weeks.

Findings: A total of 201 patients were analyzed (mean [SD] age, 58.1 [10.7] years; 62.7% male). After 8 weeks of treatment, the percentage change from baseline in triglycerides (TGs) and non-HDL-C was significantly greater in the ROSUMEGA group than in the rosuvastatin group (TGs: -26.3% vs -11.4%, P < 0.001; non-HDL-C: -10.7% vs -2.2%, P = 0.001). In the linear regression analysis, the lipid-lowering effect of ω-3 fatty acids was greater when baseline TG or non-HDL-C levels were high and body mass index was low. The incidence of adverse events was not significantly different between the 2 groups.

Implications: In patients with residual hypertriglyceridemia despite statin treatment, a combination of ω-3 fatty acids and rosuvastatin produced a greater reduction of TGs and non-HDL-C than rosuvastatin alone. Further study is needed to determine whether the advantages of this lipid profile of ω-3 fatty acids actually leads to the prevention of cardiovascular event. ClinicalTrials.gov identifier: NCT03026933.

Keywords: combination; hypertriglyceridemia; non–HDL-C; rosuvastatin; triglycerides; ω-3 fatty acids.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Docosahexaenoic Acids / adverse effects
  • Docosahexaenoic Acids / therapeutic use*
  • Double-Blind Method
  • Drug Combinations
  • Drug Therapy, Combination
  • Eicosapentaenoic Acid / adverse effects
  • Eicosapentaenoic Acid / therapeutic use*
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypertriglyceridemia / drug therapy*
  • Male
  • Middle Aged
  • Rosuvastatin Calcium / adverse effects
  • Rosuvastatin Calcium / therapeutic use*
  • Treatment Outcome


  • Drug Combinations
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Docosahexaenoic Acids
  • Rosuvastatin Calcium
  • Eicosapentaenoic Acid
  • Omacor

Associated data

  • ClinicalTrials.gov/NCT03026933