An experimental drug doctors hoped would be the next big advance in preventing heart attacks and strokes failed a crucial test, researchers reported Saturday.
The medicine, which reduces levels of a particle in the blood associated with heart attacks and strokes, didn't protect volunteers in a closely watched study.
"I was shocked. I had high hopes for success," says 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 research aimed to help people who seem to do everything right. They keep their cholesterol and blood pressure low, eat well, maintain a healthy weight, and exercise regularly. But many still suffer heart attacks and strokes.
"That sort of patient we see very frequently, and we were really doing our best to try to find a way to help those patients," Nissen says.
Many of these patients have elevated blood levels of a cholesterol-carrying protein called lipoprotein(a) or Lp(a), which has long been thought to increase the risk for heart disease.
"About 20% of the global population have elevated levels. And that's about a billion people. So it's a common disorder," Nissen says.
Until recently, doctors didn't have any drugs that could lower Lp(a) levels. But several drug companies have developed experimental new medications in recent years that can slash elevated Lp(a).
So Nissen and his colleagues gave 8,350 adults who already had heart disease either a placebo or a drug called pelacarsen, which cuts Lp(a).
The drug did suppress Lp(a) levels by about 78%, the researchers showed. But after five years, that drop didn't translate into saving people from suffering cardiovascular complications.
"Very disappointing, terribly disappointing," says Nissen, who presented the first details about the study at an American Heart Association meeting in Chicago Saturday and published more specifics in the New England Journal of Medicine and the NEJM Evidence.
Drugmaker Novartis, which sponsored the study, announced last month that the study results hadn't met its goals but without releasing specifics.
In a statement, Novartis 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 in science depends on pursuing challenging questions and studies [like the pelacarsen study] play a crucial role in moving the field forward, even if the results are not what we had hoped for," the company said.
The failure of the drug to help patients is stunning because so many scientists, doctors and drug companies hoped Lp(a)-lowering drugs would provide the next major weapon in the fight 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," says Harlan Krumholz, a Yale University cardiologist. "And so it was really jarring to see this."
Researchers are scratching their heads about what went wrong.
It could turn out that high Lp(a) doesn't actually cause heart attacks and strokes, but instead is a marker for something else that increases the risk.
There could be other reasons for why the study failed.
"Maybe you need to treat longer. You may need to treat earlier, before people have advanced hardening of the arteries," says Roger Blumenthal, a cardiologist at Johns Hopkins University.
Another possibility is that Lp(a)-lowering drugs may only help people with higher Lp(a) levels.
"Maybe a higher Lp(a) should have been required for entry into the trial," says David Maron, a Stanford University cardiologist who serves as the president of the American Society for Preventive Cardiology.
The pelacarsen study could also have failed because Lp(a)-lowering drugs may only benefit people whose blood pressure and bad cholesterol weren't as well controlled, several experts said.
Another explanation could be that there's something about pelacarsen, the experimental drug, that doesn't produce a benefit.
It's possible other Lp(a)-lowering drugs might.
Several other drugmakers, including Amgen and Eli Lilly, are testing other experimental Lp(a)-lowering drugs. The results of those trials are expected to become available over the next few years.
