Planet Flem/Digital Vision Vectors//Getty Images For stories on the science of healthy living, subscribe to NPR’s Health newsletter. An experimental drug that doctors hoped would be the next big breakthrough in preventing heart attacks and strokes has failed a crucial test, researchers reported Saturday. The drug, which reduces levels of a blood particle associated with heart attacks and strokes, did not protect volunteers in a closely watched study. “I was surprised. I had high hopes for success,” says Steven Nissen, a cardiologist at the Cleveland Clinic who led the study. “Cardiovascular disease remains the leading cause of death in developed countries. So we were really hoping to find additional therapies that would reduce the risk.” The research was aimed at helping 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. “We see those types of patients a lot and we were really doing everything we could to try to find a way to help them,” Nissen says. Many of these patients have elevated blood levels of a cholesterol-binding protein called lipoprotein(a) or Lp(a), which has long been thought to increase the risk of heart disease. “About 20% of the world’s population has elevated levels. And that’s about a billion people. So it’s a common disorder,” says Nissen. Researchers have been searching for a drug to reduce Lp(a) levels. Until recently, doctors did not have any medications that could lower Lp(a) levels. But several pharmaceutical companies have developed new experimental drugs in recent years that can reduce elevated Lp(a) levels. Thus, Nissen and his colleagues gave 8,350 adults who already had heart disease a placebo or a drug called pelacarsen, which lowers Lp(a). The researchers showed that the drug suppressed Lp(a) levels by approximately 78%. But after five years, that drop did not translate into saving people from cardiovascular complications. “Very disappointing, terribly disappointing,” says Nissen, who presented early details about the study at an American Heart Association meeting in Chicago on Saturday and published more details in the New England Journal of Medicine and NEJM Evidence. Drugmaker Novartis, which sponsored the study, announced last month that the study’s results had not met its objectives, but without providing specific details. In a statement, Novartis said the study “provides significant evidence” on the relationship between Lp(a) and heart disease and may “help inform future approaches to cardiovascular management.” “Progress in science depends on the pursuit of challenging questions and studies [like the pelacarsen study] “They play a crucial role in advancing the field, even if the results are not what we expected,” the company said. What went wrong? The drug’s failure to help patients is surprising because many scientists, doctors and pharmaceutical companies expected Lp(a)-lowering drugs to 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 hype was so high that this would end up being a positive,” Harlan says. Krumholz, a cardiologist at Yale University. “And it was really shocking 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 or strokes, but is a marker for something else that increases the risk. 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 drugs to lower Lp(a) only help people with higher Lp(a) levels. “Perhaps a higher Lp(a) should have been required to participate in the trial,” says David Maron, a cardiologist at Stanford University who serves as president of the American Society for Preventive Cardiology. The pelacarsen study might also have failed because Lp(a)-lowering drugs may only benefit people whose blood pressure and bad cholesterol were not as well controlled, several experts said. Another explanation could be that there is something about pelacarsen, the experimental drug, that other Lp(a)-lowering drugs are expected to do so in the coming years. “The bottom line is that the story is not over,” says Karol Watson, a cardiologist at the University of California, Los Angeles. “It’s just getting started.”
