

Drug aimed at inflammation may lower risk of heart disease and cancer

Researchers outside the study say the findings represent a major milestone - proof of a biologic concept that opens the door to new ways of treating and preventing cardiovascular disease in people who are still at risk despite standard therapies.

"This is fantastic," said Dr. David J. Maron, the director of preventive cardiology at Stanford University School of Medicine. "The green light just went on for full-fledged investigation and development of effective and cost-effective new therapies."

But experts also cautioned that potentially fatal side effects of the drug, as well as its high cost, mean it is unlikely to be widely used. Cardiovascular disease is the leading cause of death worldwide and in the United States, where it killed nearly 634,000 people in 2015. Globally, it killed 15 million.

The drug that was studied, canakinumab, is already marketed under the brand name Ilaris, but was approved to treat a type of juvenile rheumatoid arthritis and other rare disorders, not heart disease. It costs about $200,000 a year and is made by Novartis, which paid for the new study. The company declined to say whether the price would change if the drug came into more general use for heart disease.

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-1?, 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 was 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.

The researchers found that in the placebo group, for every 100 patients followed for a year, 4.5 had a heart attack or stroke, or died from cardiovascular disease. In those who received the optimal dose of the drug, the rate was lower, 3.86. When the length of time patients were treated was taken into account, the reduction in risk was 15 percent.









"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. A drug that fights inflammation can reduce the risk of heart attacks and strokes, and possibly lung cancer, in people who have already had one heart attack and are at high risk for another, a new study finds.Researchers outside the study say the findings represent a major milestone - proof of a biologic concept that opens the door to new ways of treating and preventing cardiovascular disease in people who are still at risk despite standard therapies."This is fantastic," said Dr. David J. Maron, the director of preventive cardiology at Stanford University School of Medicine. "The green light just went on for full-fledged investigation and development of effective and cost-effective new therapies."But experts also cautioned that potentially fatal side effects of the drug, as well as its high cost, mean it is unlikely to be widely used. Cardiovascular disease is the leading cause of death worldwide and in the United States, where it killed nearly 634,000 people in 2015. Globally, it killed 15 million.The drug that was studied, canakinumab, is already marketed under the brand name Ilaris, but was approved to treat a type of juvenile rheumatoid arthritis and other rare disorders, not heart disease. It costs about $200,000 a year and is made by Novartis, which paid for the new study. The company declined to say whether the price would change if the drug came into more general use for heart disease.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-1?, 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 was 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.The researchers found that in the placebo group, for every 100 patients followed for a year, 4.5 had a heart attack or stroke, or died from cardiovascular disease. In those who received the optimal dose of the drug, the rate was lower, 3.86. When the length of time patients were treated was taken into account, the reduction in risk was 15 percent."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.