Effect of Eicosapentaenoic Acid/Docosahexaenoic Acid on Coronary High-Intensity Plaques Detected Using Noncontrast T1-weighted Imaging: The AQUAMARINE EPA/DHA Randomized Study

J Atheroscler Thromb. 2024 Feb 1;31(2):122-134. doi: 10.5551/jat.64063. Epub 2023 Sep 14.

Abstract

Aim: Omega-3 fatty acids have emerged as a new option for controlling the residual risk for coronary artery disease (CAD) in the statin era. Eicosapentaenoic acid (EPA) is associated with reduced CAD risk in the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention trial, whereas the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia trial that used the combination EPA/docosahexaenoic acid (DHA) has failed to derive any clinical benefit. These contradictory results raise important questions about whether investigating the antiatherosclerotic effect of omega-3 fatty acids could help to understand their significance for CAD-risk reduction.

Methods: The Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technic EPA/DHA study is a single-center, triple-arm, randomized, controlled, open-label trial used to investigate the effect of EPA/DHA on high-risk coronary plaques after 12 months of treatment, detected using cardiac magnetic resonance (CMR) in patients with CAD receiving statin therapy. Eligible patients were randomly assigned to no-treatment, 2-g/day, and 4-g/day EPA/DHA groups. The primary endpoint was the change in the plaque-to-myocardium signal intensity ratio (PMR) of coronary high-intensity plaques detected by CMR. Coronary plaque assessment using computed tomography angiography (CTA) was also investigated.

Results: Overall, 84 patients (mean age: 68.2 years, male: 85%) who achieved low-density lipoprotein cholesterol levels of <100 mg/dL were enrolled. The PMR was reduced in each group over 12 months. There were no significant differences in PMR changes among the three groups in the primary analysis or analysis including total lesions. The changes in CTA parameters, including indexes for detecting high-risk features, also did not differ.

Conclusion: The EPA/DHA therapy of 2 or 4 g/day did not significantly improve the high-risk features of coronary atherosclerotic plaques evaluated using CMR under statin therapy.

Keywords: Cardiac magnetic resonance; Computed tomography angiography; Coronary plaque; Docosahexaenoic acid; Eicosapentaenoic acid; Statin.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Coronary Artery Disease* / diagnostic imaging
  • Coronary Artery Disease* / drug therapy
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Fatty Acids, Omega-3* / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Male
  • Plaque, Atherosclerotic* / diagnostic imaging
  • Plaque, Atherosclerotic* / drug therapy

Substances

  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Fatty Acids, Omega-3