A Promising Heart Drug Fails, Challenging a Long-Held Theory of Disease

A large medical study has shocked heart doctors around the world. A drug made by a company called Novo Nordisk was expected to help people with heart disease by reducing inflammation in the body. But the study found that the drug worked no better than a sugar pill, called a placebo. The surprising result is making scientists ask a big question: Does inflammation really cause heart disease at all?

The drug is called ziltivekimab. For years, many doctors believed that inflammation — the body's response to injury or infection — played a major role in causing a disease called atherosclerosis. Atherosclerosis happens when fatty plaques build up inside arteries, the tubes that carry blood through the body. Doctors hoped that if they could stop inflammation, they could slow down or prevent this dangerous buildup.

The study, called Zeus, involved more than 6,300 patients. All of them had heart disease or serious kidney disease. They also had high levels of chemicals in their blood that signal inflammation. The drug did exactly what scientists designed it to do — it brought those chemical levels way down. But even so, patients taking the drug were not healthier than those taking the placebo.

"I think we're all in a state of shock," said Dr. Martha Gulati, a heart doctor in Houston. She had hoped that treating inflammation, along with other heart treatments, could help "stomp out heart disease." Now she is asking a harder question: "Does treating inflammation even matter by the time you have atherosclerosis? Or is it too late?"

Not every doctor is ready to throw out the inflammation idea just yet. Dr. David Maron of Stanford University said the result was "a surprise and a big disappointment," but he believes there could have been problems with the study itself. Maybe the drug was not the right one to target heart disease, or maybe the patients were already too sick for it to help. He said years of other research still point to inflammation as a real cause of heart disease.

The idea that inflammation causes heart disease is more than 25 years old. It was first proposed by Dr. Paul Ridker at Brigham and Women's Hospital. A 2002 cover story in Time magazine helped spread his idea to the public. Dr. Sanjit Jolly, a doctor now at McMaster University in Canada, was a medical student when he read that article and said he was "really excited by this idea."

Dr. Jolly later ran his own large study in 2018, testing a different anti-inflammatory drug called colchicine, which is also used to treat a painful joint disease called gout. His study involved more than 7,000 heart patients, and inflammation markers in their blood went down. But those patients did no better than the ones taking a placebo — the same basic result as Zeus. At the time, other scientists told him something must have been wrong with his study.

Novo Nordisk said it is still running two more studies of ziltivekimab that will end in 2027. Scientists hope those results will help clear up the confusion. Dr. C. Michael Gibson, a cardiologist at Harvard, said the Zeus results made him pause, even though he has spent decades studying the link between inflammation and heart disease. For now, the question of whether inflammation truly causes heart disease remains open.