CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 4, July/August 2011
216
AFRICA
even more significant 26%, and heart fail-
ure death by 26%. These extremely posi-
tive findings across all different endpoints
were major news at the European Society
of Cardiology meeting in 2010.’
Those patients who achieved a heart
rate of less than 60 bpm showed the
best reduction in primary outcomes.
‘Because beta-blockers do not necessarily
achieve this and often cannot be titrated,
ivabradine is a valuable new choice in
this context’, Prof Deedwania noted. ‘It
achieves the lowest rate of heart failure
mortality and its adverse events are not
significant. It’s also cost effective, with
the number-needed-to-treat (NNT) per
year to prevent one primary endpoint
being 26. The NNT to prevent one heart
failure hospitalisation is 27.
Summing up, Prof Deedwania said
that reducing heart rate has clear cardio-
protective effects and that, when used
appropriately, ivabradine adds value over
and above current standard therapy. ‘The
results of the ongoing SIGNIFY study
should confirm this even further’, he
concluded.
Peter Wagenaar, Gauteng correspondent
New data support ivabradine use in chronic heart failure
The results of the SHI
f
T study on ivabra-
dine in chronic heart failure support the
benefits of this selective rate-lowering
drug in loweringmortalityandmorbidity in
this difficult-to-treat category of patients.
1
Now, new data released at the 2011
European Society of Cardiology congress
on heart failure held in Gothenburg,
Sweden has provided further support for
ivabradine’s use in terms of overall safety,
use with beta-blockers and health-related
quality-of-life determinants.
2-4
Improvements in quality of life
The aspect of quality of life is particularly
important, as this is greatly impaired in
patients with congestive heart failure.
Prof Karl Swedberg fromtheUniversity
of Gothenburg, who is particularly known
for the first use of beta-blockade in
the 1980s to treat heart failure due to
dilated cardiomyopathy, has been closely
involved in the SHI
f
T trial. Commenting
on the SHI
f
T Quality Of Life trial, Prof
Swedberg noted that improved survival
and alleviation of patient suffering is a
major goal in the management of heart
failure patients.
‘However, currently prescribed heart
failure treatments that prolong life, such
as beta-blockers, only modestly improve
quality of life for heart failure patients, if
at all, whereas therapies such as diuretics
that significantly improve quality of life
have no demonstrable effect on survival.
We need new therapies such as ivabradine
that improve quality of life and survival’.
2
Safety of ivabradine shown in the
pre-specified ECG Holter study
of patients participating in the
SHI
f
T study
Blinded ECG Holter readings performed
both at baseline and after eight months
in 501 SHI
f
T participants (Table 1) show
heart ratewas significantly reducedover 24
hours, by 9.5
±
10.1 bpm with ivabradine
versus 1.2
±
8.9 bpm in the placebo group.
Heart rate reduction tended to be greater
during the waking hours than at night.
Importantly, while some patients (one
in five) experienced periods when the rate
went below 40 bpm, no episodes of heart
rate lowering below 30 bpm or any unex-
pected abnormalities were observed with
ivabradine (Table 2).
TABLE 1. BASE-LINE CHARACTERISTICS IN THE HOLTER
SUB-STUDYAND THE MAIN SHIFT STUDY
Ivabradine
(
n
=
298)
Placebo
(
n
=
304)
Entire
population
(
n
=
6 505)
Age (years)
60
59
60
Gender (% male)
81
82
76
Heart rate (bpm)
79
79
80
LVEF (%)
28
28
29
NYHA class II (%)
46
45
49
NYHA class III–IV (%)
54
55
50
Ischaemic cause of heart failure (%)
68
66
68
History of AF (%)
7
6
8
Receiving beta-blockers (%)
93
92
90
Receiving ACEI/ARBs (%)
93
92
91
bpm: beats per minute, LVEF: left ventricular ejection fraction, NYHA:
NewYork Heart Association, AF: atrial fibrillation, ACEI: angiotensin-
converting enzyme inhibitor, ARB: angiotensin receptor blocker.
TABLE 2. RESULTS FROMAMBULATORY 24-HOUR
ELECTROCARDIOGRAPHIC HOLTER MONITORING
AFTER EIGHT MONTHS OF TREATMENT
Number of patients
Ivabradine
(
n
=
254)
Placebo
(
n
=
247)
≥
1 episode heart rate
<
30 bpm
0
0
≥
1 episode heart rate
<
40 bpm
54 (21%) 21 (8.5%)
RR interval
>
2.5 sec
3 (1.2%)
4 (1.6%)
RR interval
>
3 sec
0
1 (0.4%)
Atrial fibrillation
6 (2.4%)
5 (2%)
Atrial flutter
0
0
Atrioventricular block II or high-degree block 4 (1.6%)
9 (3.6%)
Atrioventricular block III
0
0
Non-sustained ventricular tachycardia
71 (28%) 81 (33%)
Sustained ventricular tachycardia
0
0
