Lepodisiran, a new drug, slashed levels of “stealthy cholesterol”—a hidden heart risk affecting 1 in 5 people—by up to 95% in early trials

'Stealthy' Cholesterol Affects 1 in 5 People—A New Drug May Finally Offer Treatment Here's what you need to know about the condition and the potential new treatment

Lepodisiran, a new drug, slashed levels of “stealthy cholesterol”—a hidden heart risk affecting 1 in 5 people—by up to 95% in early trials

• A new drug slashed levels of “stealthy cholesterol”—a hidden heart risk affecting 1 in 5 people—by up to 95% in early trials.
• Unlike regular cholesterol, lipoprotein(a) is driven by genetics, doesn’t respond to diet or exercise, and often goes undetected.
• Though not yet available, lepodisiran could become a breakthrough treatment for a major cause of heart disease and stroke.

An experimental drug seems to nearly eliminate a major—but often overlooked—risk factor for cardiovascular disease, heart attack, and stroke.

The new research, published in the New England Journal of Medicine, looked at the safety and efficacy of lepodisiran, a drug that targets lipoprotein(a), or Lp(a)—also known as “stealthy cholesterol.“

Roughly one in five people around the world, including about 64 million Americans, are thought to have high Lp(a)—but many may not know it. Stealthy cholesterol hides in plain sight—it often causes no symptoms and doesn't show up on regular cholesterol tests. And because historically there's been no treatment, doctors haven't routinely tested for it.

“We’ve never before had a way to lower it,” said Corey Bradley, MD, a cardiologist at NewYork-Presbyterian/Columbia University Irving Medical Center who was not involved in the new research. “Often, if we can’t treat something, we don’t necessarily measure it.”

However, with lepodisiran, an experimental medication from drugmaker Eli Lilly, cardiologists may be one step closer to effectively treating the deadly form of cholesterol. Here’s what you need to know about stealthy cholesterol and the experimental drug that may finally be able to treat it.

What Is Stealthy Cholesterol?

Lp(a) is similar to the better-known LDL (“bad”) cholesterol—each Lp(a) particle is made up of an LDL particle plus an additional protein.

This combination delivers a “triple hit” to your heart health, said Bradley—not only does Lp(a) clog arteries at high levels, but it also promotes blood clotting and inflammation, further increasing the risk of cardiovascular disease.

Lp(a) levels are also unaffected by lifestyle changes like diet and exercise. That’s because Lp(a) levels are determined by genetics and are largely constant throughout a person's life.

“You can lose 100 pounds, you can eat a well-balanced Mediterranean diet, you can stop smoking, exercise, et cetera—and your lipoprotein(a) will remain stable,” said Adedapo Iluyomade, MD, a preventive cardiologist at Baptist Health South Florida’s Miami Cardiac and Vascular Institute who was not involved in the new research.

Drugs that work to lower LDL cholesterol, like statins, are also ineffective on Lp(a) levels. But new medications like lepodisiran that specifically target Lp(a) could be “a game-changer for preventive cardiology,” said Iluyomade.

Lepodisiran: An Experimental Drug for Lp(a)

Lepodisiran is an injectable drug that aims to lower Lp(a) levels by blocking its production in the liver.

The drug first underwent human trials in 2023, where it was found to be safe and tolerable among patients, and reduced Lp(a) to undetectable levels for nearly one year.

In the new Phase 2 trial—which was also presented at the American College of Cardiology 2025 Scientific Sessions—about 300 adults with high Lp(a) received either a placebo or varying doses of lepodisiran.

Six months after the injections, patients who got the highest tested dose of the drug—400 milligrams—saw an average 94% reduction in their Lp(a) levels. At the 12-month mark, their Lp(a) levels were still almost 90% lower than when the trial began.

Some patients also got a second 400-milligram injection six months after the first. They saw an even larger benefit at the one-year mark: a roughly 95% drop in Lp(a), compared to baseline.

“What we have is a very effective therapy...and lowering [lipoprotein(a)] for a long period of time with relatively infrequent administration,” the study’s lead author Steven Nissen, MD, chief academic officer at the Cleveland Clinic’s Sydell and Arnold Miller Family Heart, Vascular, and Thoracic Institute, told Health.

Adding to lepodisiran’s efficacy, Nissen said the drug also appears to be safe and tolerable—no study participants had any serious adverse reactions, although some experienced temporary redness, itching, or pain at their injection sites.

What’s Next for Lepodisiran?

Lepodisiran is not currently available to patients, and more research is needed before researchers can answer the biggest question about the medication: Can lowering Lp(a) actually lower the risk of heart problems?

That answer, which Nissen’s team is working on in their Phase 3 trial, may take years. Meanwhile, other pharmaceutical companies are testing similar Lp(a)-targeting drugs—and some of those drugs are further along in clinical trials.

Overall, researchers are hopeful that lepodisiran or a similar drug may be available in the coming years for patients with Lp(a)—but they’re still hesitant to make predictions.

“Surprises can happen,” Nissen said. “Not everything that seems logical happens.”

What You Can Do Right Now

Even without a treatment available yet, experts say you can still take an important step for your heart health: get your Lp(a) levels checked.

A simple blood test can reveal your Lp(a) levels, and it may be covered by insurance. The National Lipid Association recommends that every adult get tested at least once in their life.

“The levels remain stable throughout life, so there’s really no reason to recheck it,” said Iluyomade.

If you have high Lp(a) levels, your doctor may take extra steps to improve other modifiable risk factors for heart disease, like lowering LDL cholesterol, blood pressure, and body weight; managing diabetes; and encouraging physical activity.

“By taking these other factors off the table, we can keep people safe until we can develop these more advanced therapies,” said Nissen.

Getting tested and knowing your Lp(a) levels also gives you a chance to be proactive about your health.

“It’s a great opportunity for patients to know what their risk is and advocate for themselves,” said Bradley.

This story originally appeared on: Health News - Author:Jamie Ducharme