Practice Update: Cardiology

ESC 2017: The Interleukin-1

Inhibitor Canakinumab Cuts

Cardiovascular Disease and Lung Cancer Risk by Reducing

Inflammation – CANTOS Trial

The interleukin-1β inhibitor canakinumab lowered risk of cardiovascular

disease and lung cancer risk by reducing inflammation. This conclusion, based

on results of the Canakinumab ANti-inflammatory Thrombosis Outcomes

Study (CANTOS) trial, conducted in 39 countries, was presented at the 2017

European Society of Cardiology (ESC) Congress, from August 26–30.

aul M. Ridker, MD, of the Center for

Cardiovascular Disease Prevention at

Brigham and Women’s Hospital, Bos-

ton, Massachusetts, said, “These findings

represent the end game of more than two

decades of research, stemming from a crit-

ical observation that half of heart attacks

occur in people who do not have high

cholesterol.”

He continued, “For the first time, we’ve

been able to definitively show that lower-

ing inflammation independent of cholesterol

reduces cardiovascular risk. This has

far-reaching implications. By leveraging an

entirely newway to treat patients – targeting

inflammation – we may be able to improve

outcomes significantly for certain very high

risk populations.”

The CANTOS trial aimed to determine

whether reducing inflammation in patients

who had a prior heart attack can lower risk

of another cardiovascular event. The eval-

uated drug was canakinumab, a human

monoclonal antibody that neutralizes inter-

leukin-1β signaling, thereby suppressing

inflammation. It is used to treat rare inherited

conditions associated with overproduction

of interleukin-1β.

Interleukin-β is known to play “multiple roles

in the development of atherothrombotic

plaque,” the investigators noted. These roles

include inducing procoagulant activity, pro-

moting monocyte and leukocyte adhesion

to vascular endothelial cells, and promoting

the growth of vascular smooth-muscle cells.

The study included 10,061 patients who had

previously suffered a heart attack and had

persistent, elevated levels of high-sensitivity

C-reactive protein, a marker of inflammation.

All patients received aggressive stand-

ard care, which included high doses of

cholesterol-lowering statins. In addition, par-

ticipants were randomized to 50, 150, or 300

mg of canakinumab, or placebo, adminis-

tered subcutaneously once every 3 months.

Patients were followed for up to 4 years.

The primary endpoint was the first occur-

rence of nonfatal myocardial infarction,

nonfatal stroke, or cardiovascular death.

The secondary endpoint was the first

occurrence of any of the above, or of hos-

pitalization for unstable angina requiring

urgent revascularization.

Canakinumab at doses of 150 or 300

mg reduced the risk of a cardiovascular

event (the primary endpoint) by 15% and

14%, respectively. Hazard ratios for the pri-

mary endpoint in the 50, 150, and 300 mg

groups were 0.93 (95% confidence interval

0.80–1.07; P = .30), 0.85 (95% confidence

interval 0.74–0.98; P = .021); and 0.86 (95%

confidence interval 0.75–0.99; P = .031),

respectively.

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PRACTICEUPDATE CARDIOLOGY