An anti-inflammatory drug can cut the risk of heart attacks and stroke among patients who have had a heart attack and are at risk of another, according to a new research published in the New England Journal of Medicine and The Lancet.
The research focused on Novartis' drug canakinumab, which it already sells under the brand name Ilaris for rare autoimmune conditions, and its potential effects on patients with heart disease. However, during the course of the study the researchers also discovered early findings that suggested the drug may lower the risk of lung cancer and the risk of dying from lung cancer.
The researchers published the cardiovascular findings in The New England Journal of Medicine and the cancer findings in the Lancet. However, the researchers cautioned that the cancer findings were "exploratory" and required follow-up studies. Vas Narasimhan, Novartis' head of global drug development said Novartis would launch a separate trial to explore the drug's effects on lung cancer in 2018.
For the study, funded by Novartis, researchers gave 10,061 participants an injection of canakinumab or a placebo every three months, in addition to their usual medications. The study participants had all presented with high levels of inflammation despite statin use—which can reduce inflammation—and well-managed LDL cholesterol levels.
Over the course of the six-year study, the researchers tested participants on low, medium, and high doses for a median of 3.7 years.
Key cardiovascular findings
The researchers found that 4.5 participants among every 100 participants in the placebo group over the course of a year had a heart attack, stroke, or died from cardiovascular disease. In comparison, among participants taking the medium dose of canakinumab, the rate declined to 3.86 per every 100 participants.
When the researchers accounted for the length of time participants were treated, they found that the overall risk for another heart attack, stroke, or heart-related death dropped by 15 percent among those taking the medium dose. According to the researchers, those taking the highest dose had a lower risk, but not by a margin substantial enough to suggest the drug was the cause, while those on the lowest dose did not demonstrate any effect.
However, the researchers also found that the drug came with a serious side effect: an increased risk of death by infection. According to the Times, canakinumab can increase risk of infection because it works by suppressing part of the immune system.
As a result, the drug did not improve overall survival because the reductions in cardiovascular and cancer deaths were offset by the increase in infection-related deaths, according to the study.
Paul Ridker—lead author of the study and director of Brigham and Women's Hospital's Center for Cardiovascular Disease Prevention—said the cardiovascular findings are "the first evidence we have that if you inhibit this inflammatory process without changing cholesterol at all, you're getting a risk reduction." Ridker, who has worked as a paid consultant for Novartis, added that the drug could treat the "missing half of heart disease," or those patients who have put their cholesterol levels in check but who still have high risk of another heart attack.
However, Ridker said if the drug is used clinically, it should be limited to patients who have had a heart attack, who present with high levels of inflammation, and whose blood tests after taking the drug demonstrate reductions in inflammation levels. He also said providers should closely observe the patient for possible infection.
Stakeholders call findings 'huge' for heart disease, but more research is needed
Several medical experts said the latest study demonstrates proof of a biologic concept for an alternative way of treating heart attack patients by targeting inflammation rather than cholesterol, as statins—a standard medication for treating and preventing heart attacks—do.
For instance, David Maron, the director of preventive cardiology at Stanford University School of Medicine, called the cardiovascular findings "fantastic." He said, "The green light just went on for full-fledged investigation and development of effective and cost-effective new therapies."
Separately, Daniel Rader, a preventive cardiology expert at the University of Pennsylvania, called the research "extraordinarily important." He said the findings provided "the first definitive clinical trial support for the concept that inflammation-targeted therapy reduces the risk of cardiovascular disease."
And Mark Creager, a former president of the American Heart Association, said, "It's a new paradigm: a new opportunity to further reduce death and disability." He added, "We've made such tremendous inroads in treating heart disease over the last couple of decades, and it’s hard to imagine we could confer additional benefits, but here you go."
David Goff, director of the division of cardiovascular sciences at the National Heart, Lung, and Blood Institute, added that the "public health impact potential is really substantial." He said based on the study findings, an estimated 3 million Americans could potentially benefit from the drug.
However, Robert Harrington of Stanford University School of Medicine in an editorial in NEJM said more research is needed. "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," he wrote.
According to Narasimhan, the drugmaker by the end of the year plans to seek regulatory approval for the drug to treat heart attack patients with high levels of inflammation. Novartis also plans to see if the drug's potential benefits for cancer patients could be reflected on the drug label.
Narasimhan added that it was too early in the process to provide cost estimates for the drug to treat heart disease (Grady, New York Times, 8/27; Johnson, "Wonkblog," Washington Post, 8/27; Miller, Reuters, 8/27).
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