By the time Monte Wooden had his first heart attack, nothing about his lifestyle explained it.
He didn’t smoke. His blood pressure was normal. He had been taking statins to manage moderately elevated cholesterol. Still, at 52, his heart failed him. It wasn’t until years later that doctors discovered something else was lurking in his bloodstream — something no one had ever tested for.
His levels of a particle called lipoprotein(a), or Lp(a), were more than five times the normal range.
Lp(a) is a tiny, cholesterol-like particle in the blood, discovered in 1963 and linked to heart disease as early as 1974. It is inherited, mostly invisible to patients, and largely ignored by doctors. For decades, no treatments existed. Not diet. Not exercise. In fact, not even the most powerful statins could change it.
Yet it may affect up to 1.4 billion people globally — an estimated 64 million in the U.S. alone. Most don’t know they carry the risk. Until now, there’s been nothing they could do about it.
That may soon change.
On Sunday, researchers announced that an experimental drug from Eli Lilly, lepodisiran, reduced levels of Lp(a) by a staggering 94% in a mid-stage clinical trial. The effects lasted for six months after just one or two injections, with no serious side effects reported.
The findings mark a potential turning point in treating a genetic risk factor long ignored because it was considered untouchable.
A Drug That Could Rewrite Heart Health
Lp(a) is a cholesterol-like particle that circulates in the blood and promotes the buildup of fatty plaques in arteries. Unlike LDL (the “bad cholesterol”), which can be lowered with statins and lifestyle changes, Lp(a) is genetically predetermined. Diet and exercise have almost no effect, but the consequences can be severe:
- Slightly elevated Lp(a) increases heart attack risk by 25%.
- Very high levels — found in 1 in 10 people — can double the risk.
- It’s linked to early heart attacks, strokes, and aortic valve disease.
Yet few people know they have it. Only 0.3% of Americans have ever been tested, according to one study. Among those with heart disease, only 3% have had the test.
“If you see someone who’s 40 years old with a heart attack, you need to know their Lp(a) level,” Dr. Steven Nissen, the Cleveland Clinic cardiologist who led the Lilly trial, told the New York Times. “All too often, it’s sky-high.”
“It’s shocking how under-recognized this is,” he added.
A Field Awakens
Lepodisiran is a small interfering RNA (siRNA) therapy — a genetic approach that blocks the body from making Lp(a) in the liver. In the trial, 141 patients received either one or two high doses, while 69 got a placebo.
The results were encouraging:
- A single 400-mg dose drove Lp(a) levels down by 94% within weeks.
- The effect persisted for six months, suggesting infrequent dosing could maintain protection.
Dr. David Maron, a preventive cardiologist at Stanford not involved in the trial, called the findings “thrilling.” Another cardiologist, Dr. Martha Gulati of Cedars-Sinai, described the study as “really elegant.”
But all of them emphasize the same thing: lowering Lp(a) is not the same as preventing heart attacks. At least, not yet. They’ve been here before — most famously with HDL, the so-called “good cholesterol.” Raising HDL in the lab didn’t translate into fewer heart attacks in the real world.
“We have to prove that reducing Lp(a) translates into better outcomes,” Nissen said. “That’s the next frontier.”
Lilly’s next step is a large-scale Phase 3 trial that will test whether lepodisiran can prevent heart attacks, strokes, and cardiovascular deaths. That trial is ongoing and expected to finish in 2029.
Other companies are racing ahead too. Novartis is testing pelacarsen, with results expected in 2026. Amgen and Silence Therapeutics are also in the race, while Lilly is testing an additional oral drug, muvalaplin, and Merck recently licensed its own experimental pill.
The flurry of activity marks a long-awaited surge of interest in Lp(a) after years of dormancy. Cardiologists like Nissen now routinely test their patients for it. They believe every adult should be screened — once is enough, since Lp(a) is genetically determined.
There is also good reason to believe targeting Lp(a) could save lives. Mr. Wooden was part of a clinical trial testing one of the new drugs that lower Lp(a) levels. While he was on the drug, he had no symptoms of heart disease, but they came back as soon as he stopped using the still-in-development medication.
The results of the new study published by Lilly appeared in the New England Journal of Medicine.
