New injection cuts cholesterol but does not stop heart attacks

Patients taking a new cholesterol injection saw their lipid levels drop sharply, but they did not experience fewer heart attacks or strokes. The finding came from a large clinical trial that surprised doctors who believed the treatment would prevent major cardiovascular events.

The drug, called pelacarsen, is made by Novartis. It targets lipoprotein(a), often abbreviated as Lp(a). This type of cholesterol is different from the common LDL, or bad cholesterol. Lp(a) levels are determined entirely by genetics. Diet and exercise do not lower them. About one in five Americans has high levels of Lp(a), according to the American Heart Association. Most people do not know they carry this risk.

The trial, known as Horizon, included 8,322 people. Each participant had high Lp(a) levels and had suffered a heart attack, stroke, or other cardiovascular problem within the previous 10 years. The average age of the participants was 60. Researchers followed them for an average of five years.

The results were presented on Saturday at a meeting of the American Heart Association. They were also published in the New England Journal of Medicine. The data showed that pelacarsen reduced Lp(a) levels by 78%. A placebo group saw a 13% reduction. Despite this large difference in blood levels, the group taking the drug did not have fewer heart attacks, strokes, cardiovascular deaths, or procedures to open blocked arteries.

Dr. Amanda Doran, an assistant professor of medicine at Vanderbilt University Medical Center, participated in the study. Vanderbilt was one of nearly 800 centers in the trial. She said she expected the drug to work. "Realmente pensé que esto sería un éxito asegurado," she said. "Estábamos muy comprometidos con este estudio, así que, obviamente, duele." Translation: I really thought this would be a sure success. We were very committed to this study, so, obviously, it hurts.

Dr. Steven Nissen, academic director of the Heart, Vascular and Thoracic Institute at Cleveland Clinic, led the Horizon trial. He described the outcome as an "extrema sorpresa," or extreme surprise. He noted that doctors had long assumed that lowering Lp(a) would reduce the risk of severe cardiovascular events. "Simplemente no hay evidencia aquí de que quienes lograron una mayor reducción hayan tenido mejores resultados," Nissen said. Translation: There is simply no evidence here that those who achieved a greater reduction had better outcomes.

The results were unexpected because controlling other cardiovascular markers, such as LDL cholesterol and blood pressure, usually leads to clear health benefits. Dr. Karol Watson, co-director of the Preventive Cardiology Program at UCLA, was not part of the research. She called the results a neutral impact she had not seen in a long time. "No había visto un ensayo con resultados tan neutralmente impactantes en mucho tiempo," she said.

Several theories exist for why the drug did not prevent disease. Watson suggested the treatment may have started too late in patients' lives. The participants were already established cardiovascular patients when the trial began. The high Lp(a) levels may have caused damage before the medication could alter their course. The data ended on a factual note: the drug lowered the marker, but it did not change the clinical outcome.

The failure of pelacarsen is a setback for preventive cardiology. Doctors have long sought a way to treat this genetic form of cholesterol. The Horizon trial was one of the largest studies of its kind. The results suggest that simply lowering Lp(a) is not enough to protect the heart. Patients with high Lp(a) will continue to rely on other treatments for now. The data from the 8,322 participants stands as a clear record of the drug's performance.