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Lipoprotein(a) Blood Levels and Cardiovascular Risk Reduction With Icosapent Ethyl
Michael Szarek1, Deepak L Bhatt2, Michael Miller3
1Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA; CPC Clinical Research, Aurora, Colorado, USA; State University of New York, Downstate Health Sciences University, Brooklyn, New York, USA.
Insights
Icosapent ethyl (IPE) effectively lowers cardiovascular event risk in individuals with elevated lipoprotein(a) [Lp(a)], regardless of Lp(a) levels. This finding is crucial for managing residual cardiovascular risk in patients on statin therapy.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Elevated lipoprotein(a) [Lp(a)] is a significant risk factor for cardiovascular events, even with controlled LDL cholesterol.
- Few therapeutic options exist to mitigate this residual risk.
- Icosapent ethyl (IPE) is an investigational drug for cardiovascular risk reduction.
Purpose of the Study:
- To analyze the cardiovascular benefits of icosapent ethyl (IPE) across various lipoprotein(a) [Lp(a)] levels.
- To evaluate the efficacy of IPE in reducing major adverse cardiovascular events (MACE) in patients with different Lp(a) concentrations.
Main Methods:
- Post hoc analysis of the REDUCE-IT trial involving 8,179 participants on statin therapy.
- Participants had elevated triglycerides and controlled LDL cholesterol.
- Randomization to IPE or placebo, with analysis of Lp(a) levels and MACE.
Main Results:
- Lipoprotein(a) [Lp(a)] concentration was a significant predictor of major adverse cardiovascular events (MACE).
- Icosapent ethyl (IPE) demonstrated consistent reduction in MACE across all analyzed Lp(a) levels.
- IPE significantly reduced first MACE in subgroups with Lp(a) ≥50 mg/dL and <50 mg/dL.
Conclusions:
- Baseline lipoprotein(a) [Lp(a)] concentration is prognostic for major adverse cardiovascular events (MACE) in patients with elevated triglycerides on statin therapy.
- Icosapent ethyl (IPE) provides consistent cardiovascular risk reduction across a spectrum of Lp(a) levels.
- IPE may be a valuable therapeutic option for patients with elevated Lp(a) and residual cardiovascular risk.
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.
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