ESC Congress 2017 In Review -- Main Edition - 15

ESC Congress 2017

Figure 1. LVEF and Mortality

Figure 2. Effect of β-blockers in Survivors
Placebo
β-blocker

Adjusted all-cause mortality
per 5% lower LVEF

Hazard Ratio
(compared to LVEF 35%)

2.0

Events/patients

HR, 95% CI; P value

Sinus rhythm

2160 / 14,261

1.24, 1.21-1.28; P < .0001

Atrial fibrillation

609 / 3304

1.09, 1.03-1.15; P = .002

1.5
1.0
0.5

Sinus Rhythm

Atrial Fibrilation
10

Change in Baseline LVEF
From Baseline (%)

Baseline rhythm

2.5

-5

In Review

0% 5% 4% 9% 9% 0%
< 2 0-2 6-3 5-3 0-4 ≥5
3 4
2
2

LVEF at Baseline (%)

0% 5% 4% 9% 9% 0%
< 2 0-2 6-3 5-3 0-4 ≥5
3 4
2
2

Baseline LVEF (%)

LVEF, left ventricular ejection fraction.

Reproduced with permission from D Kotecha, MD.

In patients in sinus rhythm, β-blockers consistently lowered the risks of all-cause and CV mortality across the
spectrum of LVEF, except for patients with preserved
LVEF. In the latter group, β-blockers appeared not to
reduce the risk of death. A disconnect was evident for AF
patients, with β-blockers not appearing to lessen the risk
of death across the entire LVEF spectrum.
Survival analyses for patients in sinus rhythm revealed
a nearly 30% risk reduction in all-cause and CV mortality in patients with reduced LVEF treated with β-blockers
(log-rank P < .001). The response pattern was similar for
patients in the mildly reduced LVEF group, where CV
death was halved with β-blockers (adjusted HR, 0.48;
95% CI, 0.24-0.97; log-rank P = .042022). No effect of
β-blockers was evident in the small subgroup of patients
in sinus rhythm with preserved LVEF (log-rank P = .51),
nor in those with AF regardless of LVEF. In the nearly
5600 patients who survived and had a second measurement of LVEF, those in sinus rhythm (n = 4,601; Figure 2A)
and AF (n = 996; Figure 2B) had greater improvements
in LVEF with β-blockers than those receiving placebo as
long as their LVEF was < 50%. For sinus rhythm, these
findings were consistent with the mortality data. A disconnect was evident for AF patients; β-blockers did not
appear to lessen the risk of death across the entire LVEF
spectrum despite increasing LVEF although the number
of patients included was lower.
Limitations include the small number of patients
with LVEF ≥ 50%, and lack of data on brain natriuretic
peptide, and diastolic and atrial function. The use of
double-blind RCT data and the examination of individual
patient data are study strengths.
The data suggest that HF patients in sinus rhythm
categorised as reduced and mildly reduced LVEF should
receive β-blockers to lower their risk of all-cause and CV
death.

Canakinumab Improves
Atherothrombotic Outcomes and
Alters Cancer Progression
Written by Maria Vinall

Canakinumab is a human monoclonal antibody that
binds to the pro-inflammatory cytokine IL-1β and lowers
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), nonfatal 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.

Official Peer-Reviewed Highlights From ESC Congress 2017

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