Heart drug that slashed a risky cholesterol particle by 78% fails to prevent heart attacks
Illustration: Press Pass USAAn experimental drug doctors hoped would be the next big advance in preventing heart attacks and strokes failed a crucial test, researchers reported Saturday — even though it did exactly what it was designed to do in the blood.
The drug, pelacarsen, cut levels of a cholesterol-carrying particle called lipoprotein(a), or Lp(a), by about 78%. But after nearly five years, that drop did not translate into saving people from heart attacks, strokes or emergency procedures to unblock clogged arteries, according to results presented at the American Heart Association meeting in Chicago and published in the New England Journal of Medicine.
"I was shocked. I had high hopes for success," said Dr. Steven Nissen, a cardiologist at the Cleveland Clinic who led the study. "Cardiovascular disease is still the leading cause of death in developed countries. And so we really were hoping to find additional therapies that would reduce risk."
The trial enrolled 8,350 adults who already had heart disease. Half received a monthly dose of pelacarsen; the other half received a placebo. They were followed for a median of 4.7 years. The drug did not reduce deaths, second heart attacks, strokes or the need for emergency procedures — and about one in five patients on the drug stopped taking it because of side effects, compared with 7.5% of those on placebo.
"Very disappointing, terribly disappointing," Nissen said.
The research was aimed at people who seem to do everything right — keeping cholesterol and blood pressure low, eating well, maintaining a healthy weight and exercising regularly — but who still suffer heart attacks and strokes. Many of them have elevated blood levels of Lp(a), a particle long thought to raise the risk of heart disease. About 20% of the world's population has elevated Lp(a) levels, Nissen said — roughly a billion people.
Until recently, doctors had no drugs that could lower Lp(a). Several companies have since developed experimental medicines that can slash it, and hopes were high that they would become the next major weapon against cardiovascular disease, which kills more than 900,000 Americans each year.
"I think it's a big deal because the expectation was so high that this would end up being positive," said Dr. Harlan Krumholz, a cardiologist at Yale University. "And so it was really jarring to see this."
Researchers are now scratching their heads about what went wrong. One possibility is that high Lp(a) does not actually cause heart attacks and strokes, but is instead a marker for something else that raises the risk. Another is that patients need to be treated longer, or earlier, before their arteries have hardened. The drug may also only help people with much higher Lp(a) levels, or people whose blood pressure and cholesterol are not already well controlled.
"Maybe you need to treat longer. You may need to treat earlier, before people have advanced hardening of the arteries," said Dr. Roger Blumenthal, a cardiologist at Johns Hopkins University. Dr. David Maron of Stanford University said a higher Lp(a) level might have been required for entry into the trial.
A second study presented at the same meeting delivered a similar disappointment. A Novo Nordisk drug, ziltivekimab, aimed at reducing inflammation in the heart, hit its target of lowering inflammation but also failed to prevent major cardiovascular events, researchers said.
Novartis, which sponsored the pelacarsen study, had already announced that the trial missed its main goal, without releasing details. In a statement, the company said the study "provides meaningful evidence" about the relationship between Lp(a) and heart disease and may "help inform future approaches to cardiovascular management."
Other drugmakers are still testing Lp(a)-lowering medicines. Amgen's Phase 3 results are expected in early 2028, and Eli Lilly's in 2029. "The take-home message is the story's not over," said Dr. Karol Watson, a cardiologist at the University of California, Los Angeles. "It's kind of just starting."
Sources: NPR, "A promising new medicine against heart disease fails unexpectedly" (Nov. 7, 2026, full text verified); Reuters, "Trial failures of Novartis, Novo Nordisk heart drugs leave experts guessing" (Nov. 7, 2026, full text verified). Event date verified: results presented Saturday, November 7, 2026, at the American Heart Association meeting in Chicago.
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