Approximately 25 percent of heart attack survivors will experience another major cardiovascular event within five years, even when their cholesterol levels are well controlled. For decades, the standard of care for secondary prevention has focused on lipid lowering therapy, primarily statins, as the primary tool for reducing recurrence risk. A landmark Phase III clinical trial has now provided definitive evidence that targeting inflammation, independently of cholesterol, significantly reduces the risk of a second heart attack or stroke in high risk patients. The findings were presented at the European Society of Cardiology Congress in Barcelona and published simultaneously in The New England Journal of Medicine.
Why Inflammation Drives Heart Attack Risk Beyond Cholesterol
The connection between chronic inflammation and cardiovascular disease has been a subject of scientific interest for years, but the evidence base for treating inflammation as a direct therapeutic target in heart attack prevention had remained incomplete. The CANTOS trial was specifically designed to test whether reducing inflammation in patients who had already experienced a heart attack would lower their risk of subsequent cardiovascular events, even in the absence of elevated cholesterol.
The trial enrolled patients who had previously had a heart attack and who showed elevated levels of high sensitivity C reactive protein, a well established blood marker of systemic inflammation, but who did not have high cholesterol. This patient selection was deliberate, isolating inflammation as the variable being targeted rather than lipid levels. All participants continued their standard heart medications, including statins, throughout the trial.
What the CANTOS Trial Found About Heart Attack Recurrence
Approximately 10,000 heart attack survivors were randomized to receive quarterly injections of canakinumab or placebo over a four year period. Canakinumab, marketed as Ilaris and already approved for rare autoimmune conditions, is a human monoclonal antibody that neutralizes interleukin 1 beta, a pro inflammatory cytokine that, when overexpressed, drives elevated inflammation and elevated hsCRP throughout the body.
Three doses were tested: 300 mg, 150 mg, and 50 mg. Patients receiving either of the two higher doses were 15 percent less likely to suffer another major cardiac event compared to those on placebo. No significant effect was observed at the 50 mg dose. Researchers also reported a 17 percent reduction in hospitalization for unstable angina requiring urgent cardiovascular procedures, and the need for expensive interventional procedures such as bypass surgery and angioplasty was reduced by more than 30 percent. These reductions in heart attack and cardiovascular event recurrence were observed above and beyond the risk reduction already provided by statin therapy.
Patients on canakinumab did experience more fatal infections than those on placebo, at approximately one in 1,000, though there was no significant difference in overall mortality between the groups.
The Unexpected Cancer Finding From the Heart Attack Trial
Because chronic inflammation is known to play a role in cancer as well as cardiovascular disease, the CANTOS research team had planned a review of blinded oncology safety data from the trial. The results were striking: patients treated with 300 mg of canakinumab showed a 77 percent reduction in lung cancer mortality and a 67 percent reduction in lung cancer incidence compared to those on placebo.
This finding was not the primary objective of the CANTOS trial but has significant implications for oncology research. Novartis, the manufacturer of canakinumab, announced plans to submit the CANTOS data for regulatory approval for cardiovascular indications and to request authorization to initiate additional Phase III studies in lung cancer based on these results.
What This Means for Heart Attack Prevention and Inflammation Targeting
According to CANTOS Study Chairman Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, the trial provides the first definitive evidence that lowering inflammation independently of cholesterol reduces cardiovascular risk. He described the implications as far reaching, suggesting that targeting inflammation represents an entirely new therapeutic pathway that could significantly improve outcomes for certain very high risk populations.
For patients who have survived a heart attack and continue to carry elevated inflammatory markers despite optimal lipid management, canakinumab and drugs in its class may represent a meaningful new option for secondary prevention.
To read more about cardiovascular research, visit the FOMAT blog. FOMAT conducts cardiology and metabolic clinical trials at sites across the United States. To learn more about active studies, visit FOMAT’s patient studies page.
For the full source, see the original article at DDDmag.com.