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For many years, cardiologists and basic science researchers suspected that inflammation plays a role in CVD, but definitive evidence proved elusive. That changed in August 2017 when findings from the CANTOS trial, presented at the European Society of Cardiology Congress and published in The New England Journal of Medicine, proved the inflammation hypothesis.
CANTOS evaluated whether canakinumab (Novartis), a fully human monoclonal antibody that targets interleukin-1 beta, would prevent CV events in MI survivors who were at increased risk for recurrent events due to persistent inflammation. Canakinumab has known anti-inflammatory effects and has approval for clinical use in rheumatologic disorders.
In CANTOS, 10,061 patients who randomly received one of three doses of canakinumab experienced a marked reduction of C-reactive protein over a median of 3.7 years of follow-up. The 150-mg dose conferred a 15% reduction in the primary endpoint of first occurrence of nonfatal stroke, nonfatal MI or CV death (see Table) and a 17% reduction in the key secondary endpoint of any component of the primary endpoint in addition to hospitalization for unstable angina resulting in urgent revascularization. Further analyses showed that canakinumab was also associated with reduced risk for lung cancer and cancer mortality, compared with placebo.
Cardiology Today assembled a panel of experts to discuss inflammation and CVD, the inflammation hypothesis, significance of the CANTOS results, the promise of new research, financial implications and how a focus on patients who show robust response to a therapy may be a cornerstone of CV medicine in the future.
Read on for insight from some of the leading experts in this area.
Biological plausibility
Carl J. Pepine, MD, MACC: When and where did the notion of inflammation relating to CVD begin?
Paul M. Ridker, MD, MPH, FACC, FAHA: The idea that inflammation was part of a broad disease process goes back a very long way, to Greek medicine. In fact, prior to the lipid hypothesis, there was a fair amount of interest in this and a group of vascular biologists and translational biologists who were thinking about this. During the explosion of the lipid hypothesis, those biologists kept at it, and it is a good thing that they did. I came in during the clinical/translational period about 20 years ago, but my colleague, Dr. Libby, was involved before that.
Transcranial
magnetic stimulation is a widely-used procedure wherein electromagnetic
coils are held up to the skull and short electromagnetic pulses are run
through the coil. It has long been understood that neurons react to
TMS, and the procedure has been used to treat psychiatric disorders,
substance abuse and other health conditions. Although preferable to
other treatment methods because TMS is noninvasive, its mechanisms have
always been poorly understood, making improvements difficult.
