ESC Congress 2017 In Review -- Main Edition - 14

Late-Breaking Clinical Trials

and 3 in the United Kingdom addressed the concept of
risk factor-driven upstream therapy-interventions that
are intended to modify the atrial substrate and lessen
the detriments of AF-related risk factors and diseases.
The therapy included the highest tolerable doses of mineralocorticoid receptor antagonists (MRAs), angiotensinconverting-enzyme inhibitors (ACEIs), and angiotensin
receptor blockers (ARBs); a target blood pressure of
< 120/80 mm Hg; statins; and physical/dietary cardiac
rehabilitation.
The study hypothesised that upstream therapy is
superior to conventional therapy in maintaining sinus
rhythm in patients with early persistent AF and HF.
The 245 patients were enrolled between 2009 and
2015. Inclusion criteria were age ≥ 40 years, confirmed
early symptomatic persistent AF and early HF, as well
as a history of treatment of underlying heart diseases.
Exclusion criteria included paroxysmal, transient, or
asymptomatic AF; anti-arrhythmic drug use, MRA drug
use, left atrial size > 50 mm, left ventricular ejection fraction (LVEF) < 25%, unstable cardiovascular conditions,
and inability to perform a cardiovascular rehabilitation
programme.
The patients were randomised to risk factor-driven
upstream therapy (n = 119) or conventional therapy (n = 126),
with stratification for LVEF ≥ 45% and < 45%. Myocardial
extracellular volume was determined in both groups 3
weeks later. Rhythm control and HF therapy were delivered in both groups, as was 7-day monitoring of heart
activity at 1 year. The primary endpoint was sinus rhythm
present during the 1-year heart activity monitoring period. The 2 groups were comparable at baseline for demographic and clinical characteristics.
The aggressive approach significantly enhanced
patient care compared with the conventional therapy
group in terms of MRA use (85% vs 4%; P < .001) and
statin use (93% vs 48%; P < .001), and greater use of
ACEIs and/or ARBs (87% vs 76%). Rhythm control during the 1-year follow-up was similar in both groups.
The aggressive upstream approach was superior
to conventional therapy for the primary endpoint of
sinus rhythm at 1 year (OR, 1.766; P = .021). Analyses
of a variety of clinical subgroups consistently favoured
upstream rhythm control. Secondary endpoints did not
differ significantly between the groups.
As expected, the upstream therapy was associated with more treatment-related safety signals (MRA
adverse events 31% vs 0%, statin adverse events 17%
vs 3%, ACEI and/or ARB adverse events 12% vs 6%),
which were usually tolerable.
According to Prof Van Gelder, the RACE 3 findings
demonstrate that the risk factor-driven upstream
therapy, which includes treatment of risk factors and

14

October 2017

necessary lifestyle modifications, is "effective and feasible" in improving the maintenance of sinus rhythm in
patients with early persistent AF and HF. Addressing
risk factors, rather than atrial remodeling, was a
favourable approach.
Prof Van Gelder added that the findings could help
shift the focus to risk factor modification to improve AF
outcomes.

Beta-Blockers May Benefit
Patients in Sinus Rhythm Who
Have Heart Failure Including
Those With Reduced LVEF
Written by Brian Hoyle

An individual patient-level meta-analysis of randomised
controlled trials (RCTs) involving over 17,000 patients
with heart failure (HF) indicates that β-blockers can
improve left ventricular ejection fraction (LVEF) and
lessen death in HF patients in sinus rhythm with both
reduced and mid-range LVEF.
The effect of β-blockers in HF patients with reduced
LVEF (< 40%), mildy reduced LVEF (40 - 49%), and preserved LVEF (≥ 50%) is unclear, according to presenter
and lead researcher Dipak Kotecha, PhD, University of
Birmingham, Birmingham, United Kingdom. Current ESC
guidelines [Ponikowski P et al. Eur Heart J. 2016] suggest
that mid-range LVEF be managed similarly to preserved
LVEF. However, no double-blind RCTs have specifically
addressed treatment of patients in these LVEF categories.
The researchers performed a meta-analysis of 11 placebo-controlled, double-blind RCTs. Each trial enrolled
> 300 patients. The trials had reported mortality as the
major endpoint with at least a 6-month follow-up.
The researchers examined individual patient-level
data (n = 18,637), which allowed a more robust analysis. After exclusions, 17,312 patients were analysed. The
researchers were able to determine when patients had
commenced β-blocker therapy, allowing categorisation of the patients to the reduced (n = 16,274), mildly
reduced (n = 721), or preserved (n = 317) LVEF groups.
Patients were also stratified based upon sinus rhythm
(n = 14,261) or atrial fibrillation (AF; n = 3,024) on the
baseline electrocardiogram.
The primary outcomes were all-cause and cardiovascular (CV) mortality. Patients were followed for a mean
of 1.5 years. Patients with the lowest LVEF at baseline
were associated with a greater risk of all-cause mortality,
particularly in those patients with baseline sinus rhythm
(Figure 1).

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