Lipoprotein(a) Blood Levels and Cardiovascular Risk Reduction With Icosapent Ethyl

J Am Coll Cardiol. 2024 Apr 23;83(16):1529-1539. doi: 10.1016/j.jacc.2024.02.016. Epub 2024 Mar 25.


Background: Elevated lipoprotein(a) (Lp[a]) concentrations are associated with increased cardiovascular event risk even in the presence of well-controlled low-density lipoprotein cholesterol levels, but few treatments are documented to reduce this residual risk.

Objectives: The aim of this post hoc analysis of REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was to explore the cardiovascular benefit of icosapent ethyl (IPE) across a range of Lp(a) levels.

Methods: A total of 8,179 participants receiving statin therapy with established cardiovascular disease or age ≥50 years with diabetes and ≥1 additional risk factor, fasting triglyceride 1.69 to 5.63 mmol/L, and low-density lipoprotein cholesterol 1.06 to 2.59 mmol/L were randomized to receive 2 g twice daily of IPE or matching placebo. Relationships between continuous baseline Lp(a) mass concentration and risk for first and total (first and subsequent) major adverse cardiovascular events (MACE) were analyzed, along with the effects of IPE on first MACE among those with Lp(a) concentrations ≥50 or <50 mg/dL.

Results: Among 7,026 participants (86% of those randomized) with baseline Lp(a) assessments, the median concentration was 11.6 mg/dL (Q1-Q3: 5.0-37.4 mg/dL). Lp(a) had significant relationships with first and total MACE (P < 0.0001), while event reductions with IPE did not vary across the range of Lp(a) (interaction P > 0.10). IPE significantly reduced first MACE in subgroups with concentrations ≥50 and <50 mg/dL.

Conclusions: Baseline Lp(a) concentration was prognostic for MACE among participants with elevated triglyceride levels receiving statin therapy. Importantly, IPE consistently reduced MACE across a range of Lp(a) levels, including among those with clinically relevant elevations.

Keywords: Lp(a); icosapent ethyl; triglycerides.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Cardiovascular Diseases* / drug therapy
  • Cholesterol, LDL
  • Eicosapentaenoic Acid / analogs & derivatives*
  • Heart Disease Risk Factors
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Hypertriglyceridemia* / drug therapy
  • Lipoprotein(a)
  • Middle Aged
  • Risk Factors
  • Triglycerides


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoprotein(a)
  • eicosapentaenoic acid ethyl ester
  • Triglycerides
  • Cholesterol, LDL
  • Eicosapentaenoic Acid