CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 6, July 2012
360
AFRICA
SHI
f
T: ivabradine’s additional clinical benefits regardless of
background beta-blocker dose
In systolic heart failure, reduction in
relatively high heart rates improves
clinical outcomes when achieved with
beta-blockers, and even more so when
the sinus node inhibitor ivabradine is also
added.
1
The mechanism for the effect of
beta-blockers in systolic heart failure is
unclear but there is an association between
improvement of outcomes and degree of
drug-induced heart rate reduction.
In the Systolic Heart failure treatment
with the I
f
inhibitor Trial (SHI
f
T),
reduction of heart rate by ivabradine,
administered in addition to beta-blockers
when heart rate exceeded 70 beats/min on
beta-blockers alone, reduced subsequent
adverse outcomes. A remaining clinical
question is whether beta-blocker dose
at randomisation impacts on the effect
of ivabradine. Investigators explored
this question using the SHIfT database,
assessing the impact of background beta-
blocker dose on response to ivabradine.
InMay 2012, theHeart Failure congress
of the European Society of Cardiology
(ESC) Heart Failure Association was held
in Belgrade, Serbia. At the congress,
the sub-analysis of SHI
f
T was presented
by Prof Karl Swedberg (University of
Gothenburg, Sweden) and simultaneously
published online in
Journal of the
American College of Cardiology
.
2
The analysis indicates that the effects
of ivabradine on the primary clinical
outcome of SHI
f
T and its components
were not significantly impacted on by
beta-blocker dose. The primary endpoint
and heart failure hospitalisations were
significantly reduced by ivabradine in
all subgroups with
<
50% of target beta-
blocker dose including no beta-blocker.
No suggestion of a significant trend was
apparent when the analysis was restricted
to those taking a beta-blocker.
The placebo-corrected treatment
effect of ivabradine on heart rate was
significantly related to baseline heart rate
but not to beta-blocker dose. Therefore
baseline heart rate was the most important
contributor to the treatment effect.
When a heart failure patient’s heart rate
is greater than 70 beats/min ‘reduction in
heart rate with ivabradine will provide
additional clinical benefit regardless
of beta-blocker dose’, said Prof Karl
Swedberg when presenting the analysis.
3
‘The magnitude of heart rate reduction
with ivabradine beyond that achieved
by beta-blockers primarily determines
subsequent outcomes’.
The clinical implications of these
findings reflect the importance of heart
rate. Among patients with systolic heart
failure, the dose to which a beta-blocker
can be titrated is dependent on patient
co-morbidities and other demographics.
By adding the heart rate-lowering
agent ivabradine in patients whose
heart rate exceeds 70 beats/min despite
beta-blockade (as well as among those
who cannot tolerate beta-blockade),
the additional heart rate reduction is
beneficial. The magnitude of heart rate
reduction by ivabradine beyond what is
achieved by a beta-blocker rather than
background beta-blocker dose, primarily
determines subsequent outcome.
1.
Swedberg K, Komadja M, B
ӧ
hm M,
et al
.
J Am Coll Cardiol
. 2012:
59
: 1938–1945.
2.
Swedberg K,
et al
. Effects on outcome of
heart rate reduction by ivabradine in patients
with congestive heart failure: is there an
influence of beta-blocker dose?
J Am Coll
Cardiol
2012, e-pub. DOI : 10:1016/j.
jacc.2012.01.020.
3.
Heartwire website.
HEALTHCARE
