CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 5, September/October 2010
302
AFRICA
SHIFTING the burden of heart failure
Ivabradine, the pure heart rate-lowering drug, shown to reduce morbidity and mortality in heart failure
‘The results of the SH
I
f
T study, announced
this week at the European Society of
Cardiology (ESC) 2010 congress in
Stockholm, are likely to change the clini-
cal treatment of chronic heart failure
as they provide the first positive results
for many years in this difficult field
of treatment. The great interest in the
outcome of this study was evident from
the large number of delegates attending
this hot-line session on the first day of
the congress.
SH
I
f
T has now shown for the first time
that treatment with ivabradine, added to
close-to-optimal guideline-directed thera-
pies, was able to further reduce the risk of
cardiovascular death and hospitalisation
from worsening heart failure in patients
with moderate to severe heart failure
(LVEF
≤
35%) and a raised heart rate
(above 70 beats per minute).
1
Ivabradine
is a specific inhibitor of the
I
f
current in
the sino-atrial node.
The significant relative risk reduction
(RRR) of 18% in this primary composite
outcome in patients receiving ivabradine
therapy was primarily the consequence
of the 26% reduction in hospital admis-
sions; 16% of patients taking ivabradine
were admitted to hospital with worsen-
ing heart failure compared to 21% in the
placebo group. The absolute risk reduc-
tion achieved was 4.2%. This means that
26 patients would need to be treated for
one year to prevent one cardiovascular
death or one hospital admission for heart
failure.
Importantly, the benefit of ivabradine
therapy was seen early on in the first three
months of therapy (Figs 1, 2). The other
component of the composite endpoint,
cardiovascular death, was reduced by 9%,
which was not statistically significant.
The 10% reduction in all-cause mortal-
ity achieved in the ivabradine arm (16%)
compared to 17% in the placebo arm did
not reach statistical significance. There
were no differences in the incidence of
sudden death between the two treatment
arms. Heart failure-related deaths were
however significantly reduced from 5%
in the placebo arm to 3% in the ivabradine
arm (RRR: 26%).
This SH
I
f
T study of systolic heart fail-
ure treatment with the
I
f
current inhibitor
ivabradine was undertaken to investigate
whether lowering heart rate with ivabra-
dine could reduce cardiovascular deaths
and hospital admissions from worsening
heart failure among patients with chronic
heart failure, systolic dysfunction, normal
sinus rhythm and an elevated heart rate.
The study included 6 505 patients and
was conducted over a median follow-up
period of 22.9 months. Patients were
mainly men, with an average age of 60
years, and in NYHA classes II and III.
Duration of heart failure was three years
and patients had to have experienced a
hospitalisation event in the 12 months
prior to entering the study. Heart failure
was mainly of ischaemic origin with 32%
of patients (2 086) in both the ivabradine
and placebo arms being categorised as
having heart failure of non-ischaemic
origin.
Presenting the results, Prof Michel
Komajda, professor of Cardiology,
Université Pierre et Marie Curie, Paris,
stressed that the investigators from 37
countries, which excluded the United
States of America, where ivabradine is not
registered, and Africa, had been encour-
aged to prescribe the best current stand-
ard of care as recommended by the ESC
guidelines. These guidelines also form the
basis of the South African heart failure
treatment guidelines.
The excellent background standard of
care was evident at randomisation, with
90% of patients receiving beta-blocker
therapy, 93% on ACE inhibitors/angio-
tensin receptor blocker (ARB) therapy,
84% on diuretics and 60% receiving anti-
aldosterone agents. Device usage was low
as per protocol (3%).
Patients entering the study were given
a starting dose of 5 mg ivabradine twice
daily, which was up-titrated or lowered,
depending on the heart rate response.
Heart rate was measured by ECG at
regular four-monthly intervals throughout
the study.
‘The results of SH
I
f
T are vital as there
is still a clear unmet clinical need in the
treatment of heart failure, which, despite
advances in therapy with five drug classes
which form the basis of recommended
therapy, 50% of patients still die during
the first four years. In addition, quality of
life can be very poor; commonly 25% of
patients are re-hospitalised within three
months after their first admission for
heart failure-related complications’, Prof
Komajda concluded.
1. Swedberg K, Komajda M, Bohmm, Borer
JS,
et al
. Ivabradine and outcomes in
chronic heart failure (SH
I
f
T): a randomised
placebo-controlled study.
Lancet
2010;
e-pub
29/8/2010-DOI:10.1016/S0140-
6736(10)61198-1.
Fig. 1. Cardiovascular mortality/heart failure hospitalisation.
Fig. 2. Hospitalisation for heart failure.
