Promising medicine against heart disease fails unexpectedly in major trial

Trial misses its main goal

Researchers tested pelacarsen in 8,350 adults with existing heart disease, comparing it with a placebo. The experimental medicine reduced levels of lipoprotein(a), or Lp(a), by about 78%. After five years, however, the reduction did not prevent cardiovascular complications. Study leader Steven Nissen, a Cleveland Clinic cardiologist, said he had been shocked by the result and had high hopes for success.

A widespread risk factor

Lp(a) is a cholesterol-carrying protein long thought to raise the risk of heart disease. Nissen said about 20% of the global population—roughly a billion people—have elevated levels. The study focused on people who may maintain healthy cholesterol and blood pressure, eat well, exercise and keep a healthy weight, yet still experience heart attacks or strokes. Until recently, doctors had no medicines to lower Lp(a), though several companies have developed experimental options.

Researchers weigh explanations

The result raises questions about whether high Lp(a) causes heart attacks and strokes or instead signals another underlying risk. Cardiologist Roger Blumenthal of Johns Hopkins University said treatment might need to start earlier or continue longer.

Other possibilities include requiring higher Lp(a) levels for trial participants, or finding that medicines work only for certain patients. Experts also suggested the drugs might help people whose blood pressure or bad cholesterol is less well controlled, or that pelacarsen itself may not provide a benefit.

High expectations, broader stakes

Nissen presented initial findings at an American Heart Association meeting in Chicago on Saturday; further details appeared in the New England Journal of Medicine and NEJM Evidence. Novartis, the study sponsor, had said the trial missed its goals last month, before releasing specifics.

Yale cardiologist Harlan Krumholz said the outcome was jarring because expectations had been so high. Cardiovascular disease remains the leading cause of death in developed countries and kills more than 900,000 Americans each year. Novartis said the findings could inform future approaches to cardiovascular care.