Heart Drug That Cut Lp(a) by 78% Fails to Prevent Heart Attacks in Major Trial
Novartis' pelacarsen did not reduce cardiovascular events in 8,350 patients over five years, a blow to one of cardiology's most anticipated approaches.
An experimental drug that cardiologists hoped would become the next major advance against heart attacks and strokes failed a crucial test, researchers reported Saturday at the American Heart Association meeting in Chicago.
The medicine, pelacarsen, sharply lowers a cholesterol-carrying protein in the blood called lipoprotein(a), or Lp(a), which has long been linked to cardiovascular disease. Yet in a closely watched trial it did not protect volunteers. "I was shocked. I had high hopes for success," said Dr. Steven Nissen, a cardiologist at the Cleveland Clinic who led the study. "Very disappointing, terribly disappointing."
The trial enrolled 8,350 adults who already had heart disease and gave them either pelacarsen or a placebo. The drug cut Lp(a) levels by about 78%, but after five years that reduction did not translate into fewer heart attacks, strokes or other cardiovascular complications. Nissen presented the first details at the AHA meeting and published more in the New England Journal of Medicine and NEJM Evidence. Drugmaker Novartis, which sponsored the study, said last month that it missed its goals but gave no specifics.
The research aimed to help people who seem to do everything right: low cholesterol and blood pressure, a healthy weight, good diet and exercise, yet still suffer heart attacks and strokes. Many have high Lp(a). "About 20% of the global population have elevated levels," Nissen said. "And that's about a billion people." Until recently doctors had no drugs to lower it, but several companies developed experimental treatments that can slash Lp(a). Cardiovascular disease kills more than 900,000 Americans each year.
Experts said the failure was jarring because expectations were so high. "It was really jarring to see this," said Harlan Krumholz, a Yale University cardiologist.
Researchers are unsure what went wrong. One possibility is that elevated Lp(a) does not itself cause heart attacks and strokes but is a marker for something else that does. Others point to trial design. Dr. Roger Blumenthal of Johns Hopkins said patients may need to be treated longer or earlier, before advanced hardening of the arteries sets in. Dr. David Maron of Stanford, president of the American Society for Preventive Cardiology, said the study may have needed to require higher Lp(a) levels for entry. Another possibility is that Lp(a)-lowering drugs help only people whose blood pressure and bad cholesterol are not already well controlled.
Novartis said the study "provides meaningful evidence" about the relationship between Lp(a) and heart disease and could "help inform future approaches to cardiovascular management." The company added that progress depends on pursuing hard questions "even if the results are not what we had hoped for."
Several drug companies have developed other medications that cut Lp(a), and the explanation for this failure will shape how the field judges them. Doctors said the result leaves open whether lowering Lp(a) can protect patients at all.
