The drug works differently from the cholesterol-lowering statin medicines that have become mainstays in treating and preventing heart disease. Unlike statins, it has no effect on cholesterol. Instead, it reduces inflammation — the response by the immune system to injury or infection — which researchers have long suspected of playing a role in cardiovascular disease and cancer. About half of people who have heart attacks have normal cholesterol levels, and researchers think that in some of them, inflammation may contribute to heart and artery disease.
But because the drug suppresses part of the immune system, it increases the risk of infections, including fatal ones. Deaths from infection in the study appeared to match lives saved by the drug, so there was no difference in overall mortality between the groups that got the drug and the placebo.
An editorial by Dr. Robert A. Harrington of Stanford University in The New England Journal of Medicine, which published the cardiovascular results of the study on Sunday, described the cardiovascular benefit as “modest,” called for more information about the fatal infections and said the drug was too expensive to be used in such a common disease.
Dr. Eric Peterson, a cardiologist and the director of the Duke Clinical Research Institute at Duke University, also said he thought the drug would not be widely used, but added, “There might be ways to develop other drugs that could be safer and cheaper to lower inflammation.”
The Novartis drug is much stronger and works much faster, and by a different route, than more familiar anti-inflammatory medicines like aspirin and ibuprofen. It inhibits a substance called interleukin-1β, which causes systemic inflammation.
Statins can also reduce inflammation, but not always as much as the newer drug. The new study included only people who had blood tests showing high levels of inflammation even though they were already taking statins and had lowered their “bad” LDL cholesterol to acceptable levels. The blood tests measured high-sensitivity C-reactive protein, a marker of inflammation, and high was defined as two milligrams or more per liter of blood.
There were 10,061 participants from 39 countries, with an average age of 61. A quarter were women, and 40 percent of all participants had diabetes.
They were picked at random to receive either a placebo or an injection of the drug every three months, in addition to their usual statins and other heart medicines. Three different doses of the new drug were tested, and the patients were treated for a median of 3.7 years.
“This is the first evidence we have that if you inhibit this inflammatory process without changing cholesterol at all, you’re getting a risk reduction,” said Dr. Paul M. Ridker, the first author of the study and director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston.
Dr. Daniel J. Rader, an expert in preventive cardiology at the University of Pennsylvania, who was not part of the study, said it offered “the first definitive clinical trial support for the concept that inflammation-targeted therapy reduces the risk of cardiovascular disease. I think that’s extraordinarily important.”
If the drug is used in practice, Dr. Ridker said it should be limited to patients like the ones in the study, who have already suffered heart attacks and have high levels of inflammation and therefore high risk of heart attacks and strokes. Even within that group, he said he would limit its use further, to patients whose blood tests showed that the medicine significantly lowered inflammation. And they would have to be monitored carefully and treated quickly for signs of infection.
The study also found that the drug could reduce cases of, and deaths from, lung cancer. No patients were known to have cancer when they entered the study. The highest dose appeared to cut lung cancer incidence by two-thirds, and deaths by three-quarters. But because heart disease was the main focus of the study, the authors called the cancer results “exploratory” and said more study is needed to see if they hold up.
Dr. Ridker presented the study on Sunday in Barcelona at a meeting of the European Society of Cardiology. The cardiovascular results were published in The New England Journal of Medicine, and the cancer results in The Lancet.
Dr. Lori Mosca, director of preventive cardiology at Columbia University Medical Center-NewYork-Presbyterian Hospital, said, “It is exciting that we have a new target to treat in the prevention of heart attacks,” but she worried about the cost.
Another, older and much cheaper anti-inflammatory drug, methotrexate, is also being studied to see if it can reduce cardiovascular risk, and Dr. Mosca said that if it works, it might be a more practical treatment. Dr. Ridker is also overseeing that study, which is being paid for by the federal government.
Regarding cancer, Dr. Charles M. Rudin, the chief of thoracic oncology at Memorial Sloan Kettering Cancer Center in New York, agreed that the results need to be confirmed.
“But the finding is pretty impressive, and the biology makes sense,” Dr. Rudin said. “We know inflammation is a driver of lung cancer progression.”
If the finding holds up, he said, the drug might reduce cancer risk in former smokers.
Worldwide, lung cancer kills about 1.7 million people a year, and is expected to take nearly 156,000 lives in the United States in 2017.
Although the study found that the drug also lowered risk in people who still smoked, Dr. Rudin said that did not mean they could just take the drug, keep smoking and figure they were safe. Quitting is still the best way to lower the risks of both lung cancer and heart disease, he said.