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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.
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
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.”
PracticeUpdate Editorial Team
"
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
ESC Congress 2017 • PRACTICEUPDATE CONFERENCE SERIES
5