ESC Congress 2017 In Review -- Main Edition - 17

ESC Congress 2017

(HR, 0.98; 95% CI, 0.71 to 1.35; P = .91), cardiovascular
death (HR, 0.88; 95% CI, 0.70 to 1.12; P = .30) or allcause mortality (HR, 0.92; 95% CI, 0.80 to 1.11; P = .33).
Leukopenia and fatal infections were more common
with canakinumab, while fatal malignancy and arthritis
(including osteoarthritis and gout) were less common.
In an exploratory analysis stratified by on-treatment
hsCRP, patients with an hsCRP less than the median
achieved value of 1.8 mg/L at 3 months appeared to have
a greater benefit (HR, 0.73; 95% CI, 0.63 to 0.83; P = .0001)
compared with those above the median achieved hsCRP
(HR, 0.95; 95% CI, 0.84 to 1.08; P = .47); however, formal
statistical testing for effect modification by achieved
hsCRP was not presented.
Tumor initiation, promotion, malignant conversion,
invasion, and metastasis can all be impacted by inflammation [Grivennikov SI et al. Cell. 2010]. IL-1 is abundant at tumour sites, where it may affect the process
of carcinogenesis, tumour growth, and invasiveness
and the patterns of tumour-host interactions [Apte RN
et al. Cancer Metastasis Rev. 2006]. Subclinical chronic
inflammation, as defined by an elevated hsCRP, is associated with an increased risk of inflammatory cancers,
including lung cancer [Chaturvedi AK et al. J Clin Oncol.
2010]. As a result of these observations, it has been suggested that blocking IL-1β might be a good treatment
approach for human metastatic disease [Dinarrello
CA. Cancer Metastasis Rev. 2010]. Therefore, a clinical
events committee of oncologists was established at trial
initiation to adjudicate incident cancer in CANTOS.
Notably, patients in the CANTOS study were at
unusually high risk for certain inflammatory cancers,
such as lung cancer, due to older age, high rates of past
and current smoking and chronic inflammation as evidenced by an elevated hsCRP. Canakinumab (300 mg)
reduced death from any cancer by 51% (HR, 0.49; 95%
CI, 0.31 to 0.75; P = .0009) and fatal lung cancer by 77%
(HR, 0.23; 95% CI, 0.10 to 0.54; P = .0002) [Ridker PM
et al. Lancet. 2017]. The effect appeared to be dosedependent for both endpoints where the P value for
trend with increasing canakinumab doses were .0007
and .0002, respectively. These findings are exploratory
and will need to be replicated in future studies.
CANTOS was designed to directly test the inflammatory hypothesis of atherothrombosis. In this study, SC
canakinumab administered once every 3 months lowered the inflammatory biomarkers hsCRP and IL-6 but
did not reduce atherogenic lipids in patients with stable
CAD and an elevated hsCRP at baseline. In summary,
during the average 3.7-year follow-up period, the 150 mg
dose of canakinumab showed significant reductions in
the primary and secondary study endpoints, as well as
the individual endpoints of MI, unstable angina requiring urgent coronary revascularisation and any coronary

In Review

revascularisation. Stroke, CV death, and all-cause mortality were not significantly reduced with canakinumab.
Leukopenia and fatal infections were increased with
canakinumab, while fatal malignancies and arthritis
were reduced.
As a consequence, patients being treated with
canakinumab will require monitoring for early signs
and symptoms of infection as is the current policy for
individuals taking other biologic anti-inflammatory
agents. Exploratory analyses suggested that residual
inflammatory risk, defined by an elevated on-treatment
hsCRP, may be associated with greater benefit. Another
exploratory analysis suggests that patients at high risk
for inflammatory cancers may experience a reduction in
incident fatal malignancies, including lung cancer.
In Dr Ridker's opinion, the CANTOS trial demonstrates
that targeting the IL-1β to IL-6 pathway with canakinumab reduces CV event rates and potentially reduces rates
of incident lung cancer and lung cancer mortality. These
data provide proof that inflammation inhibition, even
in the absence of lipid lowering, can improve atherothrombotic outcomes and potentially alter the progression of some fatal cancers. Furthermore, the exploratory
analyses with acheived hsCRP levels and malignancy
may provide a framework for a personalised approach
to initiating or continuing canakinumab in patients with
stable CAD and elevated hsCRP.

Apixaban Decreases Stroke
Risk in AF Patients Undergoing
Cardioversion
Written by Nicola Parry

Michael D. Ezekowitz, MBChB, DPhil, Sidney Kimmel
Medical College at Thomas Jefferson University, Lankenau
and Bryn Mawr hospitals, Philadelphia, Pennsylvania, USA,
reported results from the EMANATE trial [NCT02100228],
showing that, compared with usual care (heparin/vitamin
K antagonist), apixaban was noninferior regarding the
risk of stroke in patients with atrial fibrillation (AF) undergoing cardioversion, with even fewer stroke or systemic
embolic (SE) events in patients randomised to apixaban.
Rates of bleeding were similar in both groups.
According to Dr Ezekowitz, the EMANATE trial aimed
to prospectively compare the rates of stroke, SE, major
bleeding, clinically relevant nonmajor (CRNM) bleeding, and death in anticoagulation-naïve patients (having received < 48 hours of anticoagulation therapy) in
patients with AF scheduled for cardioversion [Dauriz M
et al. Diabetes Care. 2017].
The trial included 1,500 patients (intention-to-treat
[ITT] population) who were randomised to receive oral

Official Peer-Reviewed Highlights From ESC Congress 2017

Table of Contents for the Digital Edition of ESC Congress 2017 In Review -- Main Edition