Genetic cholesterol eliminated by new drug, reducing heart attack risk, study finds

Home Health Genetic cholesterol eliminated by new drug, reducing heart attack risk, study finds

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By Chu E. - June 5, 2025

Researchers have achieved a landmark advance in cardiovascular medicine by unveiling an experimental drug that almost completely wipes out lipoprotein(a), or Lp(a)—a cholesterol-like particle driven by genetics. Often called the “silent risk,” high Lp(a) levels can lurk undetected, raising the chances of heart attacks and strokes even in otherwise healthy individuals. This promising new treatment, recently detailed in leading medical journals, offers renewed hope for millions who previously faced limited or no solutions for managing inherited cholesterol risks. The discovery marks a pivotal shift in preventing genetically linked heart disease.

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1. What is Lipoprotein(a) and Why Does It Matter?

Genetic cholesterol eliminated by new drug, reducing heart attack risk, study finds — Colorful cholesterol particles and lipoproteins are shown magnified, highlighting details often examined in a routine blood test. | Image source: Photo by Nataliya Vaitkevich on Pexels

Lipoprotein(a), known as Lp(a), is a unique cholesterol-like substance that circulates in the blood. What sets Lp(a) apart is its genetic origin—unlike LDL (“bad” cholesterol), your levels are mostly inherited and remain steady over time. Elevated Lp(a) is recognized as a powerful, independent risk factor for heart attacks and strokes, making it a hidden danger for many. For further details, visit the American Heart Association.

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2. The Scale of the Problem: How Common is Elevated Lp(a)?

Roughly 20-25% of the global population—equating to 64 million Americans and as many as 1.4 billion people worldwide—have elevated Lp(a) levels. Despite its widespread impact, awareness remains low, with most affected individuals unaware of their genetic risk. This hidden epidemic underscores the urgent need for better screening and targeted treatments.

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3. Why Lifestyle Changes Don’t Lower Lp(a)

Unlike LDL cholesterol, Lp(a) cannot be lowered by diet, exercise, or weight loss.
This makes it a particularly challenging cardiovascular risk factor because even the healthiest habits won’t affect its levels. While lifestyle improvements can help manage other cholesterol types, Lp(a) remains stubbornly high when dictated by genetics. This unique resistance highlights the need for targeted therapies.

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4. The Genetic Link: Inherited Risk

Your Lp(a) level is set by a single gene, meaning the risk is almost entirely inherited. If you have high Lp(a) early in life, it typically stays elevated throughout your lifetime—unlike other cholesterol types that may fluctuate. This strong genetic component makes early detection crucial.
Read more from the NIH research summary.

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5. Lp(a) vs. LDL: What’s the Difference?

While both Lp(a) and LDL are lipoproteins, Lp(a) is especially dangerous due to its greater tendency to cause plaque buildup and blood clots in arteries. LDL cholesterol can often be managed with lifestyle changes and medication, but Lp(a) remains largely unaffected by these measures due to its genetic roots.
As Dr. Steven Nissen of Cleveland Clinic notes, understanding these differences is vital for effective heart disease prevention.

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6. The ‘Untreatable Frontier’ of Heart Risk

Lp(a) has long been dubbed “one of the last untreatable frontiers of cardiovascular risk”. Until recently, there were no approved medications to lower it, leaving patients and cardiologists frustrated by this stubborn genetic threat. For more expert insight, see the Cleveland Clinic perspective.

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7. Introducing Lepodisiran: The Experimental Drug

Lepodisiran, created by Eli Lilly, represents a major innovation in genetic cholesterol treatment.
This experimental drug uses RNA interference technology to silence the LPA gene, which is directly responsible for Lp(a) production. By interrupting the gene’s activity, lepodisiran can almost completely eliminate Lp(a) from the bloodstream in early clinical trials. These results have generated significant excitement in the cardiology community. Read more about the trial at The New England Journal of Medicine.

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8. How Lepodisiran Works at the Genetic Level

Lepodisiran’s innovation lies in its use of RNA interference to target the LPA gene directly.
By “silencing” this gene, the drug blocks the liver’s ability to produce Lp(a) particles, dramatically reducing their presence in the bloodstream.
This method is part of a new wave of gene-targeted therapies revolutionizing cardiovascular treatment.
To explore the science behind this, see Nature Reviews Cardiology.

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9. The Landmark Clinical Trial: Who Participated?

The phase 2 clinical trial for lepodisiran included 320 adults from ten countries, such as the US, China, and Germany, ensuring a broad and diverse participant group. All enrolled individuals had extremely high Lp(a) levels—on average, three times above the normal upper limit. This international approach strengthens the study’s relevance and impact.
For full study details, visit The New England Journal of Medicine.

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10. Unprecedented Results: Nearly 100% Reduction

A single high-dose injection of lepodisiran produced a stunning outcome—participants’ Lp(a) levels dropped by nearly 100% at six months. With a second dose, this dramatic effect was maintained for a full year, marking the most significant reduction ever observed in Lp(a) therapy. These results set a new benchmark for genetic cholesterol treatment. For more on these findings, see Fox News coverage.

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11. How Long Does the Effect Last?

With just one injection of lepodisiran, Lp(a) levels plummeted and stayed low for at least six months.
A second dose at the six-month mark helped maintain this remarkable reduction for a full year. This long-lasting impact suggests that patients may need fewer treatments, making therapy more convenient and sustainable. More details can be found at the American College of Cardiology.

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12. No Lifestyle or Dietary Changes Required

Participants benefited from lepodisiran without making any changes to their diet or exercise habits, underscoring how the drug targets genetic cholesterol directly. For those with inherited high Lp(a), this offers a significant advantage over other therapies.

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13. Safety Profile: Mild Injection Site Reactions

Lepodisiran showed a favorable safety profile in the phase 2 trial. Only 12% of participants reported mild reactions at the injection site, such as redness or tenderness. Importantly, no major safety issues or serious side effects were observed, making the drug well-tolerated overall.

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14. Importance of Diverse Research Participation

The initial lepodisiran trial included relatively few Black participants, even though this group has higher rates of elevated Lp(a). Researchers acknowledge this gap and are expanding enrollment of Black patients in ongoing phase 3 studies. This effort aims to make the results more representative and ensure the therapy’s effectiveness across all populations.
Read more at American Family Physician.

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15. Are More Doses Better?

So far, the clinical trial evaluated only one or two doses of lepodisiran. It remains unclear if more frequent or prolonged dosing could offer even greater or more durable Lp(a) reduction. Future research will focus on finding the optimal dosing schedule for sustained benefit.

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16. Gene Silencing: A New Era in Heart Disease Prevention

Lepodisiran is at the forefront of a new era in heart disease prevention, using gene-silencing technology to tackle hereditary cardiovascular risks at their source.
Other therapies employing similar RNA interference strategies are also in the pipeline, which could soon provide a range of options for patients with genetic heart risk factors.
For background on these groundbreaking approaches, see Nature Reviews Cardiology.

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17. A Call for Universal Lp(a) Testing

Major organizations like the European Society of Cardiology and the National Lipid Association urge all adults to test their Lp(a) levels at least once. Because Lp(a) is set by genetics and remains constant, a single test can reveal lifelong cardiovascular risk. Testing is straightforward—and could empower people to make informed health decisions. Learn more at National Lipid Association.

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18. Lp(a) Levels: One Test, Once in a Lifetime

Unlike traditional cholesterol, which requires ongoing monitoring, Lp(a) only needs to be measured once. Levels remain constant regardless of age or lifestyle, making it a highly reliable genetic marker for heart risk. This unique aspect means a simple, one-time test can provide lifelong insight.
Source: Harvard Health Publishing.

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19. Lp(a) and Women’s Heart Health

Elevated Lp(a) poses a particular risk for women, especially when combined with other unhealthy lifestyle factors. Many women may not realize their heightened vulnerability to heart disease related to genetic cholesterol. Raising awareness allows for earlier intervention and better prevention strategies tailored to women’s needs. For more context, visit American Heart Association News.

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20. Comparing Lepodisiran to Statins

While statins are proven to lower LDL cholesterol and reduce heart attack risk, they have no effect on Lp(a) levels. Lepodisiran is unique because it directly targets Lp(a), addressing a treatment gap for those with genetically high Lp(a) who don’t benefit from statins alone.
For statin details, see the CDC’s resource on statin use.

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21. Potential Population Impact

If lepodisiran receives approval, it could benefit millions worldwide who currently lack treatment options for genetic cholesterol. By cutting heart attack and stroke risk, its impact could extend to over 1 billion people with elevated Lp(a). This marks a major advance in global cardiovascular health.
Find more information at AHA Journals.

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22. What’s Next? The Phase 3 Clinical Trial

A much larger phase 3 clinical trial is now underway to confirm if lepodisiran’s dramatic Lp(a) reduction leads to real-world decreases in heart attacks and strokes.
Only with these results can the drug move toward regulatory approval and wider use.
For current trial information, visit ClinicalTrials.gov.

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23. Remaining Questions: Clinical Outcomes

Although the reduction in Lp(a) is remarkable, the current study did not assess whether this leads to fewer heart attacks or strokes. Experts emphasize that outcome trials measuring these real-world clinical benefits are essential before lepodisiran can be widely recommended.
For more expert perspectives, visit American College of Cardiology.

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24. Recommendations for Doctors and Patients

Experts encourage patients, especially those with a family history of heart disease, to discuss Lp(a) testing with their doctors. Early detection of elevated Lp(a) can inform preventive strategies and may determine eligibility for emerging therapies like lepodisiran.
Proactive conversations could make a critical difference in managing cardiovascular risk.
For more recommendations, visit National Lipid Association.

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25. The Role of Family History

A family history of heart disease significantly raises the odds of having elevated Lp(a), since this risk is passed down genetically. If someone in your family has experienced heart attack or stroke, it’s wise to get tested for Lp(a). Learn more about the importance of family risk at American Heart Association.

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26. Raising Awareness: A Hidden Risk Factor

Many individuals with high Lp(a) remain unaware of their risk because standard cholesterol tests do not measure this particle. Public health campaigns and better education are urgently needed to highlight the importance of genetic cholesterol and available testing.
Increased awareness could empower more people to protect their heart health.
Learn more at CDC Cholesterol Resources.

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27. The Future: A New Era in Cardiovascular Prevention

The introduction of lepodisiran and similar gene-targeted drugs signals a new era in cardiovascular prevention. By addressing genetic risk factors at their source, these therapies have the potential to prevent countless heart attacks and strokes, reshaping the landscape of heart disease treatment worldwide.
For more on what the future holds, explore Nature Reviews Cardiology.

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Conclusion

The discovery of lepodisiran marks a pivotal advance in the fight against genetic heart disease, bringing new hope to millions affected by elevated Lp(a). Although further research is essential to confirm its full impact on heart health, this innovative drug could finally offer a solution for a once “untreatable” inherited risk. As phase 3 trials continue, universal Lp(a) testing and heightened awareness will be vital for reducing cardiovascular events globally.

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Disclaimer

This article is for informational purposes only and does not substitute for professional medical advice.
Always consult your healthcare provider before making changes to your health routine or starting new medications. Clinical research is ongoing, and recommendations may evolve as new evidence emerges.
Stay informed—and take proactive steps for your heart health.

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