Investigators from Brigham and Women’s Hospital announced results of a clinical trial culminating from 25 years of cardiovascular research work. At the European Society of Cardiology meeting and in a paper published simultaneously in the New England Journal of Medicine, Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at BWH, and colleagues presented findings from CANTOS (Canakinumab Anti–inflammatory Thrombosis Outcomes Study), a trial designed to test whether reducing inflammation among people who have had a prior heart attack can reduce risk of another cardiovascular event in the future. The team reports a significant reduction in risk of recurrent heart attacks, strokes and cardiovascular death among participants who received a targeted anti–inflammatory drug that lowered inflammation but had no effects on cholesterol.

“These findings represent the end game of more than two decades of research, stemming from a critical observation: Half of heart attacks occur in people who do not have high cholesterol,” said Ridker. “For the first time, we’ve been able to definitively show that lowering inflammation independent of cholesterol reduces cardiovascular risk. This has far–reaching implications. It tells us that by leveraging an entirely new way to treat patients – targeting inflammation – we may be able to significantly improve outcomes for certain very high–risk populations.”

CANTOS, designed by Ridker and his colleagues, is sponsored by Novartis Pharmaceuticals, the manufacturer of the drug canakinumab, which targets inflammation. The research team enrolled more than 10,000 patients who previously had a heart attack and had persistent, elevated levels of high sensitivity C–reactive protein (hsCRP), a marker of inflammation. All patients in the trial received aggressive standard care, which included high doses of cholesterol–lowering statins. In addition, participants were randomized to receive 50, 150 or 300 mg of canakinumab (or a placebo for the control group), administered subcutaneously once every three months. Patients were followed for up to four years.

The team reports a 15 percent reduction in risk of a cardiovascular event – including fatal or non–fatal heart attacks and strokes – for patients who received either the 150– or 300–mg dose of canakinumab. They also saw a 17 percent reduction in a composite endpoint that further included hospitalization for unstable angina requiring urgent cardiovascular procedures. The need for expensive interventional procedures, such as bypass surgery and angioplasty, was cut by more than 30 percent in the trial. Importantly, these reductions are above and beyond the reduction in risk seen after taking statins alone. No effect was observed for the lower 50–mg dose.

In the general population, about 25 percent of heart attack survivors will have another cardiovascular event within five years, despite taking statins or other medications.

The drug used in this study – canakinumab – is a human monoclonal antibody that neutralizes interleukin–1beta.

Overall, the drug was found to be safe in the CANTOS population, but the researchers did note an increase in fatal infection among approximately one in every 1,000 patients treated. On the other hand, cancer deaths were cut in half by canakinumab such that there was a non–significant reduction in death from any cause.