CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 5, September/October 2010
304
AFRICA
Prof Jeffrey Borer, head of the Depart-
ment of Medicine, State University of
NewYork, Downstate Medical Centre
Prof Jeffrey Borer helped to design
the SH
I
f
T study and was a member of
the executive committee despite there
being no USA investigating sites. His
expertise relates mainly to device trials
in heart failure. He talked to
CVJAfrica
about his experience with this trial.
‘SH
I
f
T was a well-performed trial
and the results are very impressive.
During the trial, I became more and
more impressed with Servier’s over-
sight of the trial. They worked hard to
encourage the executive to ensure that
investigators used best-practice treat-
ment protocols so that the addition of
ivabradine was truly a study of the drug
above standard best practice. Therefore
the additive effect of ivabradine is
really solid in this trial; there can be
little doubt about the benefits.’
‘The number of events that occurred
during the trial, about 1 650 events in
total, gave us a solid data set and
confidence intervals were so narrow
that there is very little chance of the
benefits being due to chance. The
reduced costs to heart failure patients
and funders, of the 26% reduction in
hospitalisation, is extremely important
as more than 50% of the costs of heart
failure relate to hospital admissions.’
South African experts’ views on SH
I
f
T
Dr Tony Dalby, Milpark Hospital,
Johannesburg
‘It is interesting, but one would have
liked to have seen a significant drop in
cardiovascular mortality. However, these
patients are in and out of hospital and the
benefit in reducing hospitalisation is very
important. We do not have experience of
using ivabradine in this group of patients
in South Africa so we will have to feel
our way.’
Prof DP Naidoo, head of Cardiology,
University of KwaZulu-Natal
‘This is a landmark study in heart failure
because we have all been saying that
raised heart rate is an important determi-
nant of heart failure outcomes. Evidence
from beta-blocker trials has shown over
many years that lowering heart rate bene-
fits morbidity and mortality. A substan-
tial percentage of patients cannot tolerate
beta-blockers in full doses; this occurs
frequently in advanced heart failure.’
‘Adding beta-blockers in this situation
can cause an immediate worsening of their
heart failure. Ivabradine’s pure heart rate-
lowering action without negative inotropic
action or affecting conduction across the
AV node is very useful for these patients.
SH
I
f
T has shown that a further lowering of
the heart rate is accompanied by a reduc-
tion in heart failure-related hospitalisation
and deaths. Ivabradine is safe; the ocular
disturbances are restored to normal after
withdrawal of the drug in the 3% of
patients affected.’
Prof Karen Sliwa, chairperson of the
Heart Failure Society of South Africa
‘There is a particular use for ivabradine
in South Africa in non-ischaemic cardio-
myopathy, including peripartum cardio-
myopathy, where you would like to lower
heart rate without lowering an already low
blood pressure.’
‘The SH
I
f
T study is also relevant to
both South Africa and Africa because it
included 30% of patients with non-ischae-
mic heart failure, who benefited from
ivabradine. In Africa, acute heart failure
is a problem and ivabradine can be useful
in this setting, as the THESUS study also
showed that in this condition, a raised
heart rate above 75 bpm is a common
problem.’
Low-dose omega-3 fatty acids in margarines prove disappointing as secondary prevention
Lower doses of
ω
-3 fatty acids, given in
the form of enriched margarines, did not
reduce the overall rate of major cardio-
vascular events following myocardial
infarction, according to results from the
multicentre Alpha Omega trial. However,
there were borderline significant reduc-
tions among post-MI sub-groups, includ-
ing diabetic patients and women receiv-
ing alpha-linolenic acid (ALA) supple-
ments, said principal investigator Daan
Kromhout from Wageningen University,
the Netherlands, in a hot-line session at
the ESC.
The primary endpoint of the Alpha
Omega trial was major cardiovascular
events (MACE) including revascularisa-
tion by PCI or CABG. Important second-
ary endpoints included fatal coronary
heart disease and ventricular arrhythmia-
related events, defined as sudden death,
cardiac arrest and ICD placement.
A total of 4 837 patients (78.2% men,
21.8% women) aged between 60 and 80
years were enrolled in the double-blind
trial. All had suffered an MI approximate-
ly four years before the placebo-control-
led study began and were on medication
which included antithrombotic agents
(98%), antihypertensives (90%) and lipid-
lowering drugs (86%).
They were randomly assigned to daily
use of one of four trial margarines for
40 months. The first was a placebo and
the other three were supplemented with
various combinations of ALA, eicosapen-
tenoic acid (EPA), and docosahexaenoic
acid (DHA). The combinations were as
follows: ALA (2 g/day); EPA
+
DHA (400
mg/day); and a margarine containing EPA
+ DHA (400 mg/day)
+
ALA (2 g/day).
All margarines were similar in taste and
appearance for the four treatment groups.
These margarines were used on bread
instead of regular margarine or butter.
Results from the study, which was
simultaneously published in the
New
England Journal of Medicine
, showed
that 671 patients (13.9%) suffered a major
cardiovascular event during the follow-up
period. This primary endpoint was not
reduced byALA (
p
=
0.02) or EPA
+
DHA
(
p
=
0.93). This trial, which was carried out
in collaboration with 32 hospitals in the
Netherlands, did show a reduction in the
rate of cardiovascular events, approaching
significance in the sub-group of women
receiving ALA supplements (
p
=
0.07).
A
post hoc
exploratory analysis of data
from diabetic patients in the trial showed
reductions in cardiovascular endpoints
with EPA
+
DHA when compared with
placebo. The strongest effects – reductions
of approximately 50% – were on rates of
fatal CHD and arrhythmia-related events
in these diabetic patients.
