ESC Congress 2017 In Review – Focus on CAD&ACS - 11

ESC Congress 2017

In Review

CAD & ACS

Figure 1. CANTOS: Dose-Dependent Effects on Inflammatory Biomarkers
and Lipids (48 Months)
Placebo

Canakinumab
50 mg

Canakinumab
150 mg

Canakinumab
300 mg

A High-Sensitivity C-Reactive Protein Level
10

Percent Change From Baseline

0
-10
-20
-30
-40
-50
-60
-70

Percent Change
From Baseline

Months

B LDL Cholesterol Level
10
0
-10

Months

Percent Change
From Baseline

C HDL Cholesterol Level
10
0
-10

Months

Percent Change
From Baseline

D Triglyceride Level
10
0
-10

Months

HDL-C, high-density lipoprotein cholesterol; hsCRP, high-sensitivity C-reactive
protein; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides.
From The New England Journal of Medicine, Ridker PM et al, Antiinflammatory
Therapy with Canakinumab for Atherosclerotic Disease, EPub 27 August 2017.
Copyright © 2017 Massachusetts Medical Society. Reprinted with permission
from Massachusetts Medical Society.

Figure 2. Primary Endpoint With Canakinumab, 150 mg vs Placebo
25

HR, 0.85 (95% CI, 0.74-0.98)
P = .021

Placebo
Canakinumab, 150 mg

100

Cumulative Incidence of
Primary Endpoint (%)

systemic inflammation via reduction of IL-6, resulting in
a decrease in the downstream inflammatory biomarker,
high-sensitivity C-reactive protein (hsCRP). It is currently indicated for the treatment of IL-1β driven inflammatory diseases. Plasma levels of both hsCRP and IL-6
predict first and recurrent cardiovascular (CV) events
independent of lipid levels [Ridker P. J Am Coll Cardiol.
2016]. Paul M. Ridker, MD, MPH, Brigham and Women's
Hospital, Boston, Massachusetts, USA, presented the
results of a randomised double-blind, placebo-controlled trial, which showed that canakinumab reduces
CV event rates and potentially reduces rates of incident
lung cancer and lung cancer mortality without an effect
on lipids.
CANTOS [Ridker PM et al. N Engl J Med. 2017] was
designed to directly test whether inflammation reduction can reduce CV event rates in patients with stable
coronary artery disease (CAD) and residual inflammatory risk, defined by an hsCRP> 2 mg/L. Participants (n
= 10,061) were randomised to 1 of 3 doses of canakinumab (50, 150, or 300 mg) or placebo given subcutaneously (SC) once every 3 months. HsCRP, IL-6, and lipid
levels were assessed at regular intervals during the trial. The primary endpoint was the first occurrence of
nonfatal myocardial infarction (MI), non-fatal stroke, or
CV death (MACE). The key secondary CV endpoint was
MACE plus unstable angina requiring urgent revascularisation (MACE+). Critical non-CV safety endpoints
included cancer and cancer mortality and infection and
infection mortality.
Patients were a mean age of 61 years; most were
men. About 24% were smokers and 40% were diabetic. Median LDL cholesterol was ~82 mg/dL and hsCRP
was 4.1 mg/L. More than 93% of patients were on lipid
lowering therapy; 80% were taking a renin-angiotensin
inhibitor, and 95% an oral antithrombotic. Most (80%)
had undergone prior coronary interventions.
Canakinumab decreased hsCRP in a dose-dependent
manner, but had no effect on LDL-C or HDL-C, and only a
4-5% increase in triglycerides (Figure 1).
When given SC every 3 months, canakinumab, at a
median follow-up of 3.7 years, had a significant effect
for the primary endpoint of MACE (nonfatal MI, nonfatal
stroke, or CV death) was observed in the 150-mg group
(Figure 2). The effect was also significant for the 300-mg
group (HR, 0.86; P = .0314); however, the P value did not
meet the prespecified threshold for significance. No significant effect was observed for the 50-mg group (HR
0.93; P = .30).
The 150-mg group met multiplicity adjusted thresholds
for formal statistical significance for both the primary and
secondary CV endpoints.

15
10

5
40
0

Years

From The New England Journal of Medicine, Ridker PM et al, Antiinflammatory
Therapy with Canakinumab for Atherosclerotic Disease, EPub 27 August 2017.
Copyright © 2017 Massachusetts Medical Society. Reprinted with permission
from Massachusetts Medical Society.

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