CANTOS: Dousing the Fire Within to Reduce CVD

Michelle L. O'Donoghue, MD, MPH


August 07, 2017

Hello. This is Dr Michelle O'Donoghue, reporting for Medscape.

Today, I want to share my thoughts about the CANTOS trial.[1,2] We have so many announcements coming into our inboxes each day that it is easy for some of these to fly under the radar. But I believe that CANTOS is a trial that matters and it is worth giving it some thought.

CANTOS is a recently completed phase 3 trial of canakinumab, a human monoclonal antibody. Canakinumab blocks interleukin-1 (IL-1) beta; it essentially targets inflammation. The investigators tested the hypothesis that further blockade of the inflammatory pathway, specifically through IL-1 beta, could be beneficial in people who, despite existing therapy, already had an elevated inflammatory state, as marked by an elevated C-reactive protein level.

This concept is interesting, because we believe that inflammation plays a key role in terms of driving atherosclerosis. To date, identifying a pathway that, when blocked, specifically translates into a reduced risk for cardiovascular events has been elusive. I have been involved with two programs that tested different anti-inflammatory therapies,[3,4] but both yielded neutral results.

This trial met its primary endpoint: a combination of heart attack, stroke, and cardiovascular death. Results of CANTOS will be presented at the European Society of Cardiology meeting in Barcelona, Spain, at the end of the summer. We do not yet have the details regarding the magnitude of the benefit, but I believe that regardless of how large the relative risk reduction is, the fact that canakinumab significantly reduced cardiovascular events on a background of existing therapy is a tremendous breakthrough for the field.

Already, some people in the blogosphere are saying they're not sure this drug will be highly marketable unless studies demonstrate a huge relative risk reduction in terms of cardiovascular benefit. In my mind, that misses the point. I believe that here, we have a drug with a completely unique mode of action for patients with cardiovascular disease.

Even though statins are believed to have anti-inflammatory effects, this is really the first drug to definitively demonstrate that inflammation does matter, that inflammation does increase our risk for cardiovascular events, and that blocking some of those pathways translates into clinical benefit for patients. I know that I will be very interested to see the details of the results of CANTOS when presented at the end of the summer. I have to say that this is pretty exciting. I will be interested to hear what you think as well.

Signing off for Medscape, this is Dr Michelle O'Donoghue.


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