The New England Journal of Medicine published the results of a four-year clinical trial that supports the use of the drug canakinumab, in conjunction with regular statin use, as an effective way to reduce recurrence of cardiovascular failure among heart attack victims.
Trial subjects who received canakinumab (brand name ILARIS) showed a 15-percent reduction in the risk for a heart attack or stroke, compared to those treated with a placebo.
The trial also showed that cancer mortality rates were reduced for test subjects who were injected with canakinumab. This result was observed as part an exploratory arm of the trial, and researchers said it will require deeper study before a definitive conclusion can be reached.
The trial was sponsored by ILARIS manufacturer Novartis and conducted by researcher Paul Ridker and a team at the Center for Cardiovascular Disease Prevention at the Brigham and Women’s Hospital in Boston.
It was called the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS). It was conducted to test a hypothesis that arose after a diabetes clinical trial using canakinumab seemed to reinforce an apparent association between inflammation and the risk of heart attack and stroke.
“This has far-reaching implications,” Ridker told the Harvard Gazette. “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.”
More than 10,000 heart attack survivors who used statins to control cholesterol were enrolled in the trial. Half were given canakinumab, and half were administered placebos every three months for four years.
It wasn’t all good news. Trial participants who received canakinumab demonstrated a higher risk for serious infection and experienced reduced blood platelet counts.
Still, the research team concluded that the reduced cancer mortality rate and the reduction in heart attack or stroke recurrence rate offset the potential adverse side effects.
The trial’s outcome could shift the post-heart attack treatment emphasis from monitoring and reducing low-density lipoprotein (LDL, or “bad” cholesterol) control to an additional focus on inflammation levels.
“Cardiologists will need to learn about inflammation today, the same way we learned about cholesterol 30 years ago,” Ridker told the Harvard Gazette. “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.”
Another potentially major drawback in the use of canakinumab to reduce inflammation in heart attack victims is cost. Stanford University cardiologist Robert A. Harrington pointed out that a year’s supply of the drug, which is used primarily to treat rare diseases such as juvenile idiopathic arthritis, costs approximately $200,000 in the United States.
Harrington, writing in a related editorial in the New England Journal of Medicine, acknowledged the “scientific and clinical excitement” associated with the potential of a “new mechanism of action to attack in the treatment of coronary artery disease. Yet, he also recommended further research into the efficacy of other anti-inflammatory drugs and the adverse effects of canakinumab.
“CANTOS has helped move the inflammatory hypothesis of coronary artery disease forward scientifically,” Harrington wrote. “However, the modest absolute clinical benefit of canakinumab cannot justify its routine use in patients with previous myocardial infarction until we understand more about the efficacy and safety trade-offs and unless a price restructuring and formal cost-effectiveness evaluation supports it.”
