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Breakthrough Heart Drug Icosapent Ethyl Defies Odds, Slashes Risk in Patients With Stubborn Cholesterol Levels!

Written by Andrew Le, MD

UpdatedMay 29, 2024

In the most recent edition of the medical journal Journal of the American College of Cardiology, researchers published a groundbreaking study examining the impact of a drug called icosapent ethyl (IPE) on heart disease in relation to blood levels of a specific lipoprotein known as Lipoprotein(a) or Lp(a). Findings from this study could reshape the way doctors treat patients with heart conditions who have well-controlled "bad" cholesterol (low-density lipoprotein cholesterol, LDL-C) levels but are still at high risk for cardiovascular events due to elevated levels of Lp(a).

Lipoprotein(a), or Lp(a), is a type of particle within our blood that carries cholesterol. Elevated levels of Lp(a) are linked to an increased risk of cardiovascular events such as heart attacks or strokes. This risk persists even in patients who have their LDL-C levels—the type of cholesterol most commonly associated with clogged arteries—under control through medications like statins. Unfortunately, there are few treatments known to offset this lingering danger, leaving a gap in comprehensive care for heart disease patients.

The study, an analysis stemming from the REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial), set out to bridge this gap by evaluating the effectiveness of icosapent ethyl—a derivative of eicosapentaenoic acid (EPA), an omega-3 fatty acid—in tackling the elevated risk brought on by high Lp(a) levels. Their analysis pooled data from 8,179 patients who were already taking statins to manage either existing cardiovascular disease or diabetes (for those over 50 years old) alongside one or more additional risk factors. These participants had varying levels of fasting triglycerides and LDL-C at the time of enrollment.

These patients were selected for either treatment with icosapent ethyl, administered at a dosage of 2 grams twice daily, or a placebo and were observed for their risk of major adverse cardiovascular events (MACE)—which include incidents like heart attack, stroke, or death from cardiovascular causes. Researchers specifically examined whether baseline Lp(a) concentrations were related to the risk of experiencing a first MACE, as well as the effectiveness of icosapent ethyl among those with Lp(a) concentrations greater than or less than 50 milligrams per deciliter.

The core results of the study were revealing. Out of the 86% of enrolled participants who received baseline measurements for Lp(a), the median level was found to be 11.6 milligrams per deciliter. Importantly, the study established a clear link: higher Lp(a) concentrations were significantly associated with an increased occurrence of both first-time and subsequent MACE. However, in an encouraging development, the introduction of icosapent ethyl as a treatment did not show variation in effectiveness across the range of Lp(a) levels—the drug reduced the likelihood of first MACE consistently, regardless of whether participants' Lp(a) levels were above or below the 50 milligrams per deciliter threshold.

The conclusions derived from the study were definitive: Elevated baseline levels of Lp(a) can indeed serve as a prognostic factor for future major adverse cardiovascular events among patients already managing their triglyceride levels with statins. More vital is the broader implication of the findings—for the first time, there is a documented treatment, icosapent ethyl, that can reduce the risk of cardiovascular events across a spectrum of Lp(a) concentrations, including in cases where these levels are significantly elevated and thereby pegged as clinically concerning.

References

Szarek M, Bhatt DL, Miller M, Brinton EA, Jacobson TA, Tardif JC, Ballantyne CM, Mason RP, Ketchum SB, Lira Pineda A, Doyle RT Jr, Steg PG; REDUCE-IT Investigators. Lipoprotein(a) Blood Levels and Cardiovascular Risk Reduction With Icosapent Ethyl. J Am Coll Cardiol. 2024 Mar 15:S0735-1097(24)00384-X. doi: 10.1016/j.jacc.2024.02.016. Epub ahead of print. PMID: 38530686