Practice Update - ESC Congress 2017

the progression of certain cancers, but these are exploratory findings that need replication.” “Maybe we don’t want everybody on this drug,” Dr. Ridker explained, speculating on how treatment might be managed for the still investigational canakinumab. “Maybe we give patients the first dose for free to see if they respond? If they respond, with a 25% or 30% risk reduction, that’s pretty good. If they do not respond, we don’t want you exposed to the toxicity, and we want you to stay away from the drug. It’s a different way of thinking about care.” “This is the first time in 40 years where we have something that’s not about lipid-lowering. We had no change in LDL cholesterol – there was a 30% to 40% reduction in interleukin-6 and C-reactive protein. Yet we had an event rate identical to what you’d get from being treated with a PCSK9 inhibitor.” “This is about personalized medicine,” he continued. “It’s saying not all second- ary-prevention patients are the same. If your problem is because your inflam- matory response has not been inhibited enough, that your C-reactive protein is high, that’s residual inflammatory risk.” He added, “Now we have something to offer those patients. If your LDL choles- terol is high after a myocardial infarction, then you can think about a PCSK9 inhibi- tor. You’re not going to give both drugs to patients. We’re trying to figure out how to give the right drug to the right patient.” " The data on cancer rates point to the possibility of slowing the progression of certain cancers, but these are exploratory findings that need replication. Paul M Ridker, MD

In contrast, cancer mortality was signif- icantly lower in patients treated with canakinumab than those treated with placebo, which Dr. Ridker said was “remarkable.” Treatment with canakinumab 150 mg and 300 mg reduced the risk of death from any cancer by 22% and 51%, respectively. The reduction was driven primarily by a reduction in the risk of lung cancer. In addition, treatment with canak- inumab resulted in a reduction in the risk of arthritis, osteoarthritis, and gout. Dr. Ridker said, “We found that in high risk patients, a drug that lowers inflam- mation but exerts no effect on cholesterol reduced the risk of major adverse cardio- vascular events. In my lifetime, I’ve seen three broad eras of preventative cardiol- ogy. First, we recognized the importance of diet, exercise, and smoking cessation. Then we saw the tremendous value of lipid-lowering drugs such as statins. Now we’re cracking the door open on the third era. This is very exciting.” “As an inflammatory biologist and car- diologist, my primary interest is heart disease but CANTOS was a good set- ting to explore a previously observed link between cancer and inflammation,” said Dr. Ridker. “The data on cancer rates point to the possibility of slowing

Due to multiplicity testing, only the 150-mg dose met statistical significance for both the primary and secondary endpoints. The benefit of the 150-mg dose was driven by a significant, 24% reduced risk of nonfatal stroke or cardiovascular death observed. Treatment with canakinumab did reduce the risk of hospitalization for unstable angina leading to urgent revascularization (odds ratio 0.64; 95% confidence interval 0.44–0.94) and the need for any coronary revascularization (odds ratio 0.68;95% confidence interval 0.58–0.81). Dr. Ridker explained that the relative reduction in clinical events ranged from 5% to 30%, depending on C-reactive pro- tein and interleukin-6 levels. Overall, the drug was found to be safe, but approximately one in every 1000 patients suffered a potentially fatal infec- tion. A small but significantly increased risk of death caused by infection or sepsis was observed when all three treatment arms were combined and compared with events in the placebo arm (0.31 vs 0.18 events per 100 patient years; P = .02). Neutropenia and thrombocytopenia were more common in patients treated with canakinumab.

PracticeUpdate Editorial Team

ESC Congress 2017 • PRACTICEUPDATE CONFERENCE SERIES 5