Inflammation Reduction cuts Risk of Heart Attack, Stroke

Trial study finds a need for expensive interventions, such as bypass surgery, cut by more than 30 percent.

Inflammation Reduction cuts Risk of Heart Attack, Stroke
Image: Women having heart pain

A new research by Harvard Gazette suggests that an anti-inflammatory drug could reduce the risk of recurrent heart attacks, strokes, and cardiovascular death. But it does not affect on cholesterol.

Scientists studied, does inflammation reduction really reduce the risk of prior heart attack or any cardiovascular disease. To do so, they collected data on the clinical trials that encompassed 25 years of cardiovascular research.

Paul M. Ridker, director of the Center for Cardiovascular Disease Prevention at BWH said, “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.”

“For the first time, we’ve been able to definitively show that inflammation reduction could 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.”

Inflammation Reduction cuts Risk of Heart Attack, Stroke
Credit: Brigham and Women’s Hospital
Paul M. Ridker and his research team at Brigham and Women’s Hospital found that reducing inflammation was key to cutting the risk of future cardiovascular events.

Scientists involved more than 10,000 patients who previously had a heart attack and had persistent, elevated levels of high sensitivity a marker of inflammation. All patients in the survey received standard treatments. In addition, participants were randomized to receive 50, 150, or 300 mg of canakinumab.

After asking participants, they reported 15 percent reduction in risk of a cardiovascular event. Scientists also saw a 17% reduction in a composite endpoint that included hospitalization for unstable angina requiring urgent cardiovascular procedures. The need for expensive interventions, such as bypass surgery and angioplasty, was cut by more than 30 percent in the trial.

Ridker said, “In my lifetime, I’ve gotten to see three broad eras of preventative cardiology. In the first, we recognized the importance of diet, exercise, and smoking cessation. In the second, we saw the tremendous value of lipid-lowering drugs such as statins. Now, we’re cracking the door open on the third era. This is very exciting.”

Usually, 25 percent of heart attack survivors will have another cardiovascular event within five years. Scientists used the drug called canakinumab drug that neutralizes interleukin-1β. If overexpressed, results in increased inflammation throughout the body as well as increased levels of hsCRP. 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.

Scientists noted, “participants who achieved greater-than-average reductions in hsCRP with canakinumab experienced the largest clinical benefit. There was almost 30 percent reduction in the risk of a recurrent heart attack, stroke, or cardiovascular death.”

Peter Libby, also of Brigham and Women’s Hospital said, “CANTOS represents a milestone in a long journey implicating interleukin-1 in cardiovascular disease. The results not only establish the role of innate immunity in human atherosclerosis and make actionable decades of research, but they also usher in a new era of therapeutics.”

Gary H. Gibbons director of the National Heart, Lung, and Blood Institute (NHLBI) said, “These clinical trial results build upon decades of basic and translational science that has provided mechanistic insights into the key role that inflammation plays in clinical events such as heart attacks and strokes.”

“Although this trial provides compelling evidence that targeting inflammation has efficacy in preventing recurrent cardiovascular events, we look forward to findings from additional trials, such as the NHLBI-funded Cardiovascular Inflammation Reduction Trial, to further refine the best therapeutic strategies for preventing cardiovascular disease.”

In future, scientists hope to study patients with sudden plaque ruptures and to look at additional biological agents that take aim at inflammatory pathways.

Ridker said, “Cardiologists will need to learn about inflammation today, the same way we learned about cholesterol 30 years ago. CANTOS is a demonstration of how personalized medicine will occur in the future, as we now need to distinguish those heart disease patients who have ‘residual cholesterol risk’ from those who have ‘residual inflammatory risk.’ These two groups will require different interventions.”