Eli Lilly’s drug
Eli Lilly‘s drug significantly lowers blood levels of Lp(a), a mysterious particle linked to heart attack risk, but further studies are required to confirm its effectiveness in preventing heart attacks and strokes.
As many as one in five people—about 64 million in the U.S.—have elevated levels of a tiny blood particle, Lp(a), which significantly raises the risk of heart attacks and strokes.
Yet, awareness is low, and doctors rarely test for it because treatment options have been nonexistent. Diet and exercise have no effect, and no approved drugs have been available.
That could soon change.
On Sunday, cardiologists announced that Eli Lilly’s experimental drug, lepodisiran, reduced Lp(a) levels by 94% with a single injection. The effect lasted six months with no significant side effects.
However, whether lowering Lp(a) also reduces heart attack and stroke risk remains unproven. Large clinical trials now underway aim to answer that question.
The Lilly research was unveiled Sunday at the annual American College of Cardiology meeting and simultaneously published in the New England Journal of Medicine. At least four other companies are also developing innovative drugs designed to block the body’s production of Lp(a), a complex of lipids and proteins linked to heart disease.
Dr. David Maron, a preventive cardiologist at Stanford not involved in the research, called lepodisiran’s ability to dramatically and persistently lower lipoprotein levels “thrilling.” Dr. Martha Gulati, a preventive cardiologist at Cedars-Sinai Medical Center, praised the study as “really elegant.”
Eli Lilly is now conducting a large-scale clinical trial to determine whether lepodisiran can prevent heart attacks, strokes, or cardiovascular deaths, with results expected in 2029. Other Lp(a)-targeting drugs may deliver findings sooner—the first, a Novartis injection given monthly, is set to report results in 2026.
Still, cardiologists caution that reducing Lp(a) may not necessarily translate into fewer heart attacks or strokes. History has shown that modifying a risk factor doesn’t always improve outcomes. For instance, drugs designed to raise HDL, or “good cholesterol,” once seemed promising because naturally high HDL levels were linked to lower heart disease risk—yet those drugs ultimately failed to provide protection.
“Lp(a)-lowering is a huge new frontier in cardiovascular medicine,” said Dr. Daniel Rader, a preventive cardiologist at the University of Pennsylvania’s Perelman School of Medicine. Dr. Rader, who serves on Novartis’s scientific advisory board, also authored an editorial accompanying the new study.
Treatments targeting Lp(a) have been a long time coming.
Identified as a heart disease risk factor in 1974, Lp(a) is influenced by genetics rather than lifestyle or environmental factors, making it difficult to manage through conventional means.
Even slightly elevated Lp(a) levels increase the risk of heart attack or stroke by about 25%. For the 10% of the population with very high levels, the risk can double.
Cardiologists often find that patients with no obvious risk factors for heart attacks or strokes—those with normal cholesterol levels, healthy blood pressure, and no smoking history—have elevated Lp(a) levels. Many also have a family history of unexplained heart disease. The same pattern appears in young heart attack patients, said Dr. Steven Nissen, a preventive cardiologist at the Cleveland Clinic and academic leader for the Lilly drug trial and other Lp(a)-targeting clinical studies.
“If you go into the coronary care unit and see someone who is 40 years old with an acute myocardial infarction, you need to know their Lp(a) level,” Dr. Nissen said. Many such patients have levels exceeding 250 nanomoles per liter—far above the upper limit of 75.
Dr. David Maron sees similar cases regularly. His clinic is filled with patients who were puzzled by their heart disease—until they discovered their Lp(a) levels were high.
One of them is Monte Wooden, a 71-year-old retired firefighter from Redding, California. Despite moderately elevated LDL cholesterol, normal blood pressure, and no smoking history, he had his first heart attack in 2006 while on a statin. His family history was striking—his paternal grandmother had a heart attack in her 40s and died at 63, his father and uncle died of heart disease, and his brother suffered a fatal heart attack.
When Dr. Maron tested Wooden’s Lp(a) level, it exceeded 400.
Preventive cardiologists like Dr. Gulati, Dr. Nissen, and Dr. Rader routinely test their patients’ Lp(a) levels, emphasizing that since genetics control Lp(a), a single test is sufficient.
Dr. Nissen is direct with his Lp(a)-positive patients:
“We say: You have a disorder with serious implications. I want to take every risk factor you have off the table.”
Yet, Lp(a) testing remains rare. Dr. Gulati noted that only 0.3% of the U.S. population has been tested, even though insurance covers the test. Even among heart disease patients, just 3% have been screened.
She and other cardiologists argue that all adults should have their Lp(a) levels checked. If elevated, doctors should aggressively manage other cardiovascular risk factors.
For Wooden, that meant taking Repatha, a powerful cholesterol-lowering drug, which brought his LDL cholesterol down to 30.
Mr. Wooden’s case, however, didn’t end there. Dr. Maron enrolled him in a clinical trial testing one of the new Lp(a)-lowering drugs.
During the trial, Wooden experienced no symptoms of heart disease—no chest pain, no breathlessness. But after the trial ended, his symptoms returned, ultimately leading to a quadruple bypass surgery.
“It’s anecdotal,” Dr. Maron said, “but it speaks to the likelihood that these drugs prevent heart attacks.”
