Reducing inflammation without lowering cholesterol significantly lowers rate of recurrent cardiovascular events

By Dr. Ananya Mandal, MDAug 28 2017

The researchers from Brigham and Women's Hospital this week have come up with a new study which shows that reducing the inflammation among patients who have already had a heart attack before could prevent the risk of getting more cardiovascular events. The study is published in the latest issue of the New England Journal of Medicine.

The study, called the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study), spanned over 25 years and was led by Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at BWH.

The CANTOS trial was designed to check if the reduction of the inflammation among people who have already had a heart attack could stop further attacks in future. Results showed that these agents do prevent recurrence of strokes, heart attacks and deaths due to cardiovascular events. These drugs reduced only the inflammation and did not actually have an effect on cholesterol levels. For persons who have had a heart attack, 25 percent individuals carry a risk of another cardiovascular event such as a stroke or a heart attack within five years of the first attack.

Ridker explained that the findings of this study are the results of over two decades of study and proves one thing – nearly half of all individuals who have heart attacks, do not have a raised cholesterol. This is a ground breaking result and changes beliefs that existed till now. This study shows that reducing the inflammation independently of cholesterol could be the key to prevention of future attacks. Ridker said that this research had greater implications as it changes the way high risk patients are treated. When treated with this new understanding, these individuals may benefit more he noted.

The CANTOS trial is sponsored by the Novartis Pharmaceuticals. The trial tested their drug canakinumab, which reduces inflammation. For this study the team of researchers included 10,061 patients who previously had a heart attack. These patients all had a persistently high level of high sensitivity C-reactive protein (hsCRP), a marker of inflammation (2 mg per litre or more). The patients enrolled in the study received standard care, which included high doses of cholesterol-lowering statins. They were further divided into four groups - 50, 150 or 300 mg of canakinumab or a placebo. These were administered with a subcutaneous injection once in three months. Patients were followed for up to four years.

Results revealed that there was a 15 percent reduction in the risk of getting another heart event such as a heart attack or a stroke that may or may not be a lethal one when the patients received either 150 or 300 mg of canakinumab. When including the risk for getting hospitalized for unstable angina that would necessitate a cardiovascular procedure, the risk was further reduced by 17 percent found the study researchers. Further, use of canakinumab reduced the risk of expensive and invasive heart procedures such as cardiac bypass surgery or an angioplasty by 30 percent. These effects were seen over and above the reduction of risk that was offered by the cholesterol lowering statin alone as seen in the placebo control group. Also the group that received the lowest dose of canakinumab at 50 mg did not show these benefits.

The reduction of hsCRP was at a median of 26 percent more in the 50 mg group, 37 percent more in the 150 mg group and 41 percent more in the 300 mg group of cannakinumab compared to placebo.

The drug canakinumab is a human monoclonal antibody preparation that works on the inflammatory markers such as interleukin-1β by neutralizing it. Interleukin-1 when in excess signals an increased inflammation throughout the body and also leads to raised hsCRP. Canakinumab was generally found to be safe and well tolerated among the study population except for the cases of infection that affected one in every 1000 users.

According to Ridker, cardiologists are being made aware of the roles that inflammation plays in heart disease similar to the way that they learnt about how cholesterol levels affect the risk of heart disease. He explained that in future heart disease risk patients would be divided into two groups – those that have a raised risk due to cholesterol and those that have a raised risk due to inflammation. Treatment thus would be “tailor made” to suit the individual needs of the patients.