An experimental drug that doctors hoped would be a major new way to prevent heart attacks and strokes has failed a crucial test, researchers reported Saturday, NPR reported. The medicine lowers levels of lipoprotein(a), or Lp(a), a cholesterol-carrying particle long thought to raise the risk of heart disease. In the trial, it did not protect the volunteers. "I was shocked. I had high hopes for success," said Steven Nissen, a Cleveland Clinic cardiologist who led the study.
About 20 percent of people worldwide, roughly a billion, have elevated Lp(a), Nissen said. Until recently, doctors had no drugs that could lower it. Several companies have since developed experimental medicines that can slash those levels. Nissen and his colleagues gave 8,350 adults who already had heart disease either a placebo or pelacarsen, a drug designed to cut Lp(a). The drug suppressed Lp(a) by about 78 percent. After five years, that drop did not translate into fewer cardiovascular complications. "Very disappointing, terribly disappointing," Nissen said. He presented the first details at an American Heart Association meeting in Chicago and published more in the New England Journal of Medicine and NEJM Evidence.
The research was aimed at patients who already do a lot of the right things — they keep cholesterol and blood pressure in check, eat well, maintain a healthy weight, and exercise — and still have heart attacks and strokes. Many of those patients have high Lp(a). Cardiovascular disease remains the leading cause of death in developed countries and kills more than 900,000 Americans each year, NPR noted. Lowering a marker is not the same as preventing those events, and this trial is the evidence for that gap.
Novartis, which sponsored the study, said last month that the results had not met its goals, without releasing specifics at the time. 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." Progress, it said, depends on pursuing hard questions, even when the results are not what researchers hoped. The verified finding is not that Lp(a) is irrelevant. It is that this drug, in this trial, cut the particle sharply and still did not save people from heart attacks and strokes over five years.
Other experimental Lp(a) drugs are still in development, and this result does not automatically sink the entire class. It does raise the bar for the next trial: cutting the particle is no longer enough to assume patients will be safer. Nissen's shock is part of the record because he had expected success. The five-year outcome is what doctors will have to put next to that hope when they talk to patients who already do everything else right and still carry high Lp(a).