Cholesterol-lowering drug fails to prevent heart attacks and strokes

An experimental drug sharply lowered a cholesterol-related particle linked to heart disease but did not prevent heart attacks, strokes or other serious cardiovascular problems in a major clinical trial. The result challenges hopes that lowering lipoprotein(a), known as Lp(a), would offer a new way to protect people at high risk.

The injected drug, pelacarsen, reduced Lp(a) levels by 78%, compared with a 13% reduction in the placebo group, according to NBC News. Yet researchers found no measurable decrease in heart attacks, strokes, cardiovascular deaths or procedures to restore blood flow to the heart. The findings were presented Saturday at an American Heart Association meeting and published in the New England Journal of Medicine.

“I was shocked. I had high hopes for success,” said Dr. Steven Nissen, a Cleveland Clinic cardiologist who led the study. “We really were hoping to find additional therapies that would reduce risk.”

The trial enrolled people with elevated Lp(a) who already had heart disease or had experienced a cardiovascular problem. NBC News put enrollment at 8,322 participants, while NPR reported 8,350. Participants were followed for about five years.

Lp(a) is largely determined by genetics. Like LDL, often called “bad” cholesterol, it contributes to plaque buildup in arteries; it can also promote blood clots. Diet and exercise do not lower inherited high levels. About one in five Americans have elevated Lp(a), according to the American Heart Association, and many do not know it. Nissen told NPR that about 20% of people worldwide — roughly a billion people — have elevated levels.

Researchers had expected the drug’s substantial effect on Lp(a) to translate into fewer cardiovascular events. “I really thought that this was going to be a slam dunk,” said Dr. Amanda Doran of Vanderbilt University Medical Center, one of nearly 800 trial sites. “We were pretty invested, so it obviously hurts.”

The trial does not establish why pelacarsen failed to improve outcomes. Some specialists said treatment may have begun too late: Participants were, on average, 60 years old, according to NBC News. Others raised the possibility that longer treatment, higher starting Lp(a) levels or differences in the drug itself could matter. Participants also received treatment to control other risks, including LDL cholesterol and blood pressure.

Novartis, which sponsored the trial, said the findings could help guide future research, even though the results were not what it had hoped for. Nissen told NBC News that no further study of pelacarsen is planned.

Doctors cautioned against treating the result as proof that Lp(a) testing has no value. “None of that invalidates Lp(a) as a robust marker of cardiovascular disease risk,” said Dr. John Wilkins of Northwestern Medicine. Knowing a patient’s level can help doctors identify risk and pursue other preventive measures, he said.

Other Lp(a)-lowering injections, including drugs under development by Eli Lilly, Amgen and Silence Therapeutics, are being studied to determine whether they prevent cardiovascular events. Eli Lilly is also studying an oral drug. “The take-home message is the story’s not over,” said Dr. Karol Watson, a UCLA cardiologist.