Cardiovascular disease continues to claim more lives globally than any other condition, with familiar culprits like high blood pressure and elevated cholesterol often taking the blame. Yet lurking in the shadows is a lesser-known risk factor that approximately 64 million Americans carry without awareness. This stealthy threat, called lipoprotein(a) or Lp(a), has long evaded both detection and treatment—until now. A groundbreaking experimental medication called lepodisiran is showing extraordinary promise in clinical trials, potentially opening a new chapter in heart disease prevention.
The hidden cholesterol most people never test for
Lipoprotein(a) has earned its nickname “stealthy cholesterol” for good reason. It silently accumulates in the bloodstream without causing noticeable symptoms, and standard cholesterol panels performed during routine check-ups don’t measure it. This oversight leaves approximately one in five people worldwide completely unaware of their elevated levels and increased cardiovascular risk.
What makes Lp(a) particularly challenging is its resistance to traditional interventions. Unlike LDL (commonly known as “bad cholesterol”), which responds to diet modifications, exercise, and statin medications, Lp(a) levels remain stubbornly fixed throughout life. They’re determined almost entirely by genetics rather than lifestyle, meaning that people born with high levels have historically had no effective way to lower them.
This genetic determination has created a frustrating paradox in cardiovascular care. Medical professionals have recognized Lp(a) as a significant risk factor for heart attacks, strokes, and aortic stenosis for decades, but without treatment options, routine testing seemed pointless. Consequently, millions of individuals remain unaware of this substantial risk lurking in their bloodstream.
How the new medication works
Lepodisiran, developed by pharmaceutical company Eli Lilly, represents a revolutionary approach to addressing this previously untreatable risk factor. The injectable medication employs advanced RNA interference technology to target the root cause of elevated Lp(a) levels directly in the liver, where this lipoprotein is produced.
The drug works by interrupting the genetic instructions that direct liver cells to manufacture Lp(a). By inhibiting production at its source, lepodisiran can dramatically reduce the amount of this dangerous particle circulating in the bloodstream. Early human trials in 2023 demonstrated both the safety and remarkable efficacy of this approach, with participants experiencing sustained reduction of Lp(a) to near-undetectable levels for almost a year after a single injection.
These promising initial results led to expanded testing in a recent Phase 2 trial presented at the American College of Cardiology 2025 Scientific Sessions. This larger study involved approximately 300 adults with elevated Lp(a) levels who received either a placebo or varying doses of lepodisiran.
Impressive results from clinical trials
The data from the Phase 2 trial has generated considerable excitement in the cardiovascular community. Participants who received the highest dose of lepodisiran (400 milligrams) experienced an astonishing average reduction in Lp(a) levels of 94% after six months. Even more remarkably, these benefits persisted, with levels remaining approximately 90% lower than baseline a full year after treatment.
Some participants received a second injection during the study period, resulting in even more dramatic results with reductions approaching 95%. This long-lasting effect suggests that lepodisiran might offer protection with minimal treatment burden, potentially requiring only annual or semi-annual injections rather than daily medication.
The safety profile of lepodisiran has proven equally encouraging throughout the trials. Participants reported no serious adverse reactions attributable to the drug, with side effects generally limited to mild, temporary injection site reactions. This favorable safety record, combined with the profound efficacy, positions lepodisiran as a potentially transformative therapy for millions at risk from elevated Lp(a).
The next crucial research question
While lepodisiran clearly demonstrates remarkable ability to lower Lp(a) levels, researchers still face a critical question: Will this reduction actually translate to fewer heart attacks, strokes, and other cardiovascular events? The medical community currently operates under the assumption that lowering Lp(a) will improve outcomes, similar to how reducing LDL cholesterol reduces heart disease risk, but definitive proof requires large-scale clinical trials.
Researchers have already initiated a comprehensive Phase 3 trial designed to answer precisely this question. This study will track cardiovascular outcomes in participants receiving lepodisiran compared to those receiving a placebo, providing concrete evidence about the clinical benefits of Lp(a) reduction. However, these results may take several years to materialize, as researchers must wait for enough cardiovascular events to occur across both groups to draw statistically valid conclusions.
In the meantime, lepodisiran remains unavailable outside clinical trials, leaving physicians to focus on managing other modifiable risk factors in patients with elevated Lp(a). This approach includes aggressive LDL cholesterol reduction, blood pressure control, and lifestyle modifications to minimize overall cardiovascular risk until targeted Lp(a) therapies become available.
Why testing matters now
Despite the wait for lepodisiran to complete the approval process, health experts increasingly advocate for Lp(a) testing. The National Lipid Association recommends that every adult undergo this simple blood test at least once in their lifetime, ideally earlier rather than later, as levels remain relatively stable throughout life.
Knowledge of Lp(a) status offers several important benefits even without specific treatment options. First, it allows healthcare providers to assess cardiovascular risk more accurately, potentially leading to more aggressive management of other risk factors. For instance, a physician might set lower LDL cholesterol targets for patients with elevated Lp(a).
Second, this information can influence family screening decisions. Since Lp(a) levels are genetically determined, first-degree relatives of individuals with high levels have a 50% chance of sharing this risk factor. Early identification allows for proactive cardiovascular care across generations.
Finally, knowing your Lp(a) status positions you to benefit promptly from treatments like lepodisiran once they become available. Patients already aware of their elevated levels can discuss these emerging therapies with their healthcare providers without delay when approval occurs.
How to advocate for your heart health
Taking control of your cardiovascular health begins with comprehensive testing. While standard lipid panels remain important, requesting specific Lp(a) measurement provides a more complete picture of your risk profile. Many insurance plans now cover this test, particularly for individuals with family histories of early heart disease or unexplained cardiovascular events.
If testing reveals elevated Lp(a) levels, focus on optimizing other aspects of heart health while awaiting specific therapies. This approach includes maintaining ideal blood pressure, achieving target LDL cholesterol levels (potentially with medication), engaging in regular physical activity, following a heart-healthy diet, and avoiding tobacco products.
Regular check-ups become especially important for those with high Lp(a), allowing for close monitoring of overall cardiovascular health and timely intervention if concerns arise. Additionally, staying informed about developing research and treatment options ensures you can access new therapies like lepodisiran when they become available.
The broader implications for personalized medicine
The lepodisiran story illustrates a broader trend in medical care toward increasingly personalized approaches to disease prevention and treatment. Rather than applying one-size-fits-all solutions, modern medicine increasingly tailors interventions based on individual risk factors, including genetic predispositions like elevated Lp(a).
This shift toward precision medicine promises more effective outcomes with fewer unnecessary treatments. By identifying specific risk factors and targeting them directly, healthcare providers can focus resources where they will provide maximum benefit while minimizing potential side effects and costs associated with unnecessary interventions.
For cardiovascular disease specifically, this approach may eventually include routine genetic and biomarker screening to identify personalized risk profiles, followed by targeted interventions addressing each person’s unique combination of risk factors. Lepodisiran represents an important step in this direction, offering the first truly effective therapy for a previously untreatable genetic risk factor.
Looking toward the future
As research on lepodisiran continues advancing through clinical trials, the cardiovascular community anticipates potentially dramatic improvements in preventive care. If Phase 3 trials confirm that Lp(a) reduction translates to fewer cardiovascular events, an entirely new pathway for heart disease prevention will open for millions of at-risk individuals worldwide.
The timing appears particularly favorable, as increased awareness of Lp(a) coincides with the development of effective treatment options. This convergence may finally break the cycle that has kept Lp(a) testing uncommon due to lack of treatments, and treatments undeveloped due to limited awareness.
For individuals currently living with elevated Lp(a) levels, this progress offers something that has long been missing: hope. The prospect of reducing this significant risk factor represents a potential turning point in cardiovascular care that could prevent countless heart attacks, strokes, and premature deaths in the coming decades.
While lepodisiran still faces several years of clinical testing before potential approval, its development marks a watershed moment in addressing one of the most common yet overlooked risk factors for heart disease. For the millions walking around unaware of their elevated Lp(a) levels, this innovative therapy may soon provide the protection their hearts have always needed.
