About 25 percent of heart attack patients will experience another cardiovascular event within five years, even if they do not have high cholesterol. Researchers at Brigham and Women’s hospital in Boston have shown that lowering inflammation, and not just cholesterol, may reduce risk of heart attack or stroke in this population.

The research was announced at the at the European Society of Cardiology (ESC) Congress in Barcelona and published simultaneously in The New England Journal of Medicine.

Treating inflammation as a way to treat heart disease is not a new idea, but the CANTOS Phase III trial has provided new evidence that it is, indeed, a valid approach.

The research team administered the drug canakinumab (marketed as Ilaris and already approved to treat rare autoimmune conditions) to randomized patients who previously had a heart attack and elevated levels of high sensitivity C-reactive protein (hsCRP) but not high cholesterol. hsCRP is a known marker of inflammation.

“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,” said Paul Ridker, MD, CANTOS Study Chairman and Director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital.

But that’s not all. The research also uncovered that the drug may slow the growth of cancer.

The CANTOS Phase III trial

About 10,000 heart attack survivors were randomized to receive quarterly injections of canakinumab or placebo over a four-year period. All study arms continued use of their heart medications, including statins.

Three doses of canakinumab were tested: 300mg, 150mg, and 50mg. Canakinumab is a human monoclonal antibody that neutralizes interleukin-1β, a pro-inflammatory cytokine that, if overexpressed, results in increased inflammation throughout the body as well as increased levels of hsCRP.

After follow up, those on the two higher doses of canakinumab were 15 percent less likely to suffer another major cardiac event compared to those taking a placebo. No effect was observed for the lower 50-mg dose.

On the flip side, those taking canakinumab experienced more fatal infections (1 in 1,000) than those taking placebo, but there was no significant difference in the rate of deaths from all causes.

Researchers also reported that they saw a 17 percent reduction in 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.

Chronic inflammation can drive cancer as well as heart disease, so researchers planned a review of blinded oncology safety analyses. Their results showed a 77 percent reduction in lung cancer mortality and 67 percent reduction in lung cancer cases in patients treated with 300mg of canakinumab. In addition to submitting the CANTOS data for regulatory approval for cardiovascular events, Novartis plans to request approval to initiate additional Phase III studies in lung cancer.   

"The results of CANTOS are exciting because we now have clear evidence that in addition to lowering cholesterol, targeting inflammation reduces patients' risk of cardiovascular disease, and perhaps even lung cancer," said Ridker.