An experimental medicine that medical experts hoped would become a major advancement in preventing heart attacks and strokes has failed a vital clinical trial, researchers announced Saturday. The medication successfully reduced levels of a specific blood particle linked to cardiovascular events, but it ultimately failed to protect volunteers in the closely monitored study.
Unexpected Trial Results
“I was shocked. I had high hopes for success,” stated Steven Nissen, a cardiologist at the Cleveland Clinic who directed the research, as reported by NPR. He added that cardiovascular disease remains the leading cause of death in developed countries, motivating researchers to find additional risk-reducing therapies.
The study focused on individuals who manage their cholesterol and blood pressure, maintain a healthy weight, eat well, and exercise regularly, yet still experience heart attacks and strokes. Many of these patients exhibit elevated blood levels of a cholesterol-carrying protein known as lipoprotein(a) or Lp(a), a factor long believed to heighten heart disease risk. According to Nissen, about 20 percent of the global population, or roughly one billion people, live with this common condition.
Until recently, no medications existed to lower Lp(a) levels. However, several pharmaceutical companies recently developed experimental drugs capable of reducing elevated Lp(a). For the study, Nissen and his team administered either a placebo or an experimental drug called pelacarsen—which cuts Lp(a)—to 8,350 adults who already had heart disease.
While the medication suppressed Lp(a) levels by approximately 78 percent, that reduction did not translate into preventing cardiovascular complications after five years. Nissen described the outcome as terribly disappointing while presenting the initial findings at an American Heart Association meeting in Chicago, with further specifics published in the New England Journal of Medicine and NEJM Evidence.
Novartis, the drugmaker that sponsored the trial, announced last month that the study had missed its goals. In a public statement, the company noted that the research provides meaningful evidence regarding the relationship between Lp(a) and heart disease and may help inform future cardiovascular management approaches. The company emphasized that scientific progress relies on pursuing challenging questions, and such studies are vital for moving the field forward despite disappointing outcomes.
Uncertainty Over Next Steps
The failure surprised the medical community because scientists and pharmaceutical companies anticipated that Lp(a)-lowering medications would serve as a major weapon against cardiovascular disease, which claims more than 900,000 American lives annually. Harlan Krumholz, a cardiologist at Yale University, called the outcome a big deal and noted that the high expectations made the results jarring.
Researchers are currently investigating potential explanations for the trial’s failure. Roger Blumenthal, a cardiologist at Johns Hopkins University, suggested that treatment might need to last longer or start earlier, before individuals develop advanced hardening of the arteries. David Maron, a Stanford University cardiologist and president of the American Society for Preventive Cardiology, noted that higher Lp(a) threshold requirements might have been necessary for trial entry. Other experts proposed that pelacarsen specifically may lack therapeutic benefit, or that these drugs might only assist individuals whose blood pressure and bad cholesterol were not as rigorously controlled, or those with even higher Lp(a) levels.
Other pharmaceutical companies, including Amgen and Eli Lilly, are currently testing alternative experimental Lp(a)-lowering medications, with results anticipated over the next few years. Karol Watson, a cardiologist at the University of California, Los Angeles, stated that the story is far from over and is essentially just beginning.
