Lp(a) and CV Risk Reduction With Icosapent Ethyl

Apr 16, 2024
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Authors:
Szarek M, Bhatt DL, Miller M, et al., on behalf of the REDUCE-IT Investigators.
Citation:
Lipoprotein(a) Blood Levels and Cardiovascular Risk Reduction With Icosapent Ethyl. J Am Coll Cardiol 2024;83:1529-1539.
Summary By:
Elizabeth A. Jackson, MD, FACC

Quick Takes

  • Icosapent ethyl (IPE) was associated with reduced MACE outcomes across a range of Lp(a) levels.
  • Baseline lipoprotein(a) concentration was prognostic for MACE among participants with elevated triglyceride levels receiving statin therapy.
  • Absolute risk reductions at 5 years with IPE were 5.7% and 6.5% for Lp(a) levels <50 mg/dL and ≥50 mg/dL, respectively.

Study Questions:

What is the cardiovascular (CV) benefit of icosapent ethyl (IPE) across a range of lipoprotein(a) [Lp(a)] levels?

Methods:

Data from REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) were used for the present post hoc analysis. A total of 8,179 participants from 473 sites in 11 countries were randomized in a 1:1 ratio to receive 2 g twice daily of IPE or matching placebo. Key inclusion criteria included age ≥45 years and established cardiovascular disease (CVD) or age ≥50 years with diabetes and ≥1 additional risk factor, fasting triglyceride 1.69–5.63 mmol/L (150–499 mg/dL), low-density lipoprotein cholesterol 1.06–2.59 mmol/L (41–100 mg/dL), and stable statin dose for ≥4 weeks.

The primary outcome was time to first major adverse cardiovascular event (MACE), consisting of death from CVD (CV death), nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization, or unstable angina. Secondary outcomes included total MACE (i.e., first and subsequent), CV mortality, nonfatal MI, and nonfatal stroke.

Results:

Among 7,026 participants (86% of those randomized) with baseline Lp(a) assessments, the median (Q1, Q3) concentration was 11.6 (5.0, 37.4) mg/dL. During a median of 4.9 (interquartile range, 3.6−5.3) years, first MACE event was experienced by 804 participants in the placebo group and 635 participants in the IPE group; corresponding counts for total MACE were 1,544 for placebo and 1,058 for IPE. 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 ≥50 mg/dL and <50 mg/dL. The relative and absolute IPE treatment effects were consistent for both subgroups, with treatment hazard ratios of 0.75 and 0.79 (interaction p = 0.68) and absolute risk reductions at 5 years with IPE of 5.7% and 6.5% for <50 mg/dL and ≥50 mg/dL, respectively.

Conclusions:

The authors conclude that 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 those with clinically relevant elevations.

Perspective:

These data add further evidence for measuring Lp(a) in higher-risk individuals. Furthermore, the findings, along with the primary results of REDUCE-IT, suggest IPE may be an effective treatment option for some patients with elevated Lp(a) in combination with statin therapy.

Clinical Topics: Dyslipidemia, Advanced Lipid Testing, Lipid Metabolism, Prevention

Keywords: Lipoprotein(a), Novel Agents, Risk Reduction Behavior


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