(2026-08-06) A Promising Heart Drug Fails Challenging A Longheld Theory Of Disease

A Promising Heart Drug Fails, Challenging a Long-Held Theory of Disease. The drug targeted inflammation, and its shocking failure has experts questioning whether inflammation really does cause heart disease.

Novo Nordisk stunned the cardiology world last week when it announced that a large study it was running on an experimental drug for heart disease had failed. The drug, widely expected to be a blockbuster, was no better than a placebo.

The drug, ziltivekimab, reduces inflammation, which is generally thought to be a cause of atherosclerosis. Stopping that inflammation was hoped to be a way to save lives.

Now the drug’s failure is raising a troubling question. Is inflammation really a cause or is it just a marker of atherosclerosis, the way gray hair is a marker of aging?

Dr. David Maron of Stanford, who is president of the American Society for Preventive Cardiology, said the result “comes as a surprise and a big disappointment.”
But he added, something could have been wrong with the study: Perhaps it just wasn’t the right drug to target heart disease inflammation, or maybe patients in the trial were too sick to be helped by anti-inflammatory medications. There is too much evidence, he said, from pathology studies of plaques in arteries, animal studies, epidemiology and other clinical trials, to toss out the inflammation hypothesis.
“Inflammation is more than a marker of disease, it is a cause of the disease,” Dr. Maron said.

As a professor at McMaster University in Canada, Dr. Jolly saw a chance in 2018 to do what he hoped would be a definitive test of inflammation. It was larger than the previous studies, involving more than 7,000 heart disease patients who were given colchicine or a placebo. Levels of CRP fell in those taking the drug, but they fared no better than those taking a placebo.
“People said, ‘Something has to be wrong with your study,’” Dr. Jolly said. “I said: ‘I am a scientist. I have to wait for trials like Zeus to come out.’”
Now, with Zeus results that are nearly identical to the results from Dr. Jolly’s similarly sized study, he is left wondering what will happen next, in the two ongoing Novo Nordisk trials of ziltivekimab.

Others are also starting to wonder if perhaps they have been pinning their hopes on a hypothesis that is wrong.

Dr. Gulati too has not given up on the hypothesis. But, she said, she is tempering some of her enthusiasm. She had hoped, she said, that by adding an inflammation treatment to treatments to lower LDL, the bad type of cholesterol, “we could stomp out heart disease.”
“I actually thought this would be the new frontier,” she said.
Now she is asking a new question: “Does treating inflammation even matter by the time you have atherosclerosis? Or is it too late?”