Systolic Heart failure treatment with
the If inhibitor ivabradine Trial
Effects on outcomes of heart rate reduction
by ivabradine in patients with congestive
heart failure:
is there an influence of beta-blocker dose?
Swedberg K, et al. J Am Coll Cardiol. 2012; 59:1938-1945
www.shift-study.com
Clinical characteristics of patients
by β-blocker status
No BB
BB <25%
of target
dose
Age, years
BB 25% to
BB
BB
<50% of target 50% to <100% ≥100% of
dose
of target dose
target dose
64
61
60
60
58
Resting HR, bpm
84.2
80.6
79.5
79.1
78.9
Systolic BP, mm Hg
121
117
120
122
125
LV EF, %
28.7
28.1
28.9
29.4
29.3
NYHA III or IV, %
58
54
49
50
51
COPD, %
33
11
11
9
5
Asthma, %
11
2
2
2
2
PAD, %
10
6
6
6
5
Hypertension, %
63
55
63
70
73
ACE/ARB, %
90
86
90
92
93
Diuretic, %
86
87
83
83
81
Swedberg K, et al. J Am Coll Cardiol. 2012; 59:1938-1945
www.shift-study.com
Effect of ivabradine on outcomes
by β-blocker doses
BB category
(% of target dose)
Placebo
Hazard
event rate (%) ratio
95 % CI
P
P
P
heterogeneity
Trend
Trend adj**
0.35
0.056
0.135
0.55
0.12
0.19
PEP (CV death, HF hospitalisation)
No β-blocker
39.3
0.71
0.55-0.93
BB, 25%
40
0.74
0.59-0.92
BB, 25% to <50%
30.8
0.81
0.68-0.98
BB, 50% to <100%
24.8
0.88
0.72-1.07
BB, ≥100%
20.1
0.99
0.79-1.24
No β-blocker
29
0.62
0.45-0.85
BB, 25%
29
0.68
0.52-0.89
BB, 25% to <50%
22
0.74
0.59-0.93
BB, 50% to <100%
18
0.83
0.65-1.05
BB, ≥100%
14
0.84
0.63-1.11
HF hospitalisation
**adjusted for interaction between baseline HR and randomised treatment
Swedberg K, et al. J Am Coll Cardiol. 2012; 59:1938-1945
www.shift-study.com
HR reduction according to
β-blocker and HR category
HR reduction (bpm)
from baseline to 28
days with ivabradine*
16
Baseline
HR category (bpm)
12
≥87
8
80 to <87
75 to <80
4
72 to <75
<72
0
No BB
BB<25% BB 25-50% BB 50-100% BB ≥100%
β-blocker category
No impact of BB dose
on HR reduction with ivabradine
Swedberg K, et al. J Am Coll Cardiol. 2012; 59:1938-1945
Impact of baseline
HR on HR reduction
with ivabradine
*Placebo corrected
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Conclusion
•
In patients with systolic HF treated with guidelinerecommended therapies, resting HR remains an important
modifiable risk factor in patients treated with β-blockers
•
When HR ≥70 bpm, reduction of heart rate with ivabradine
will provide additional clinical benefits regardless of the ßblocker dose
•
The magnitude of HR reduction with ivabradine, beyond
that achieved by β-blockers, primarily determines
subsequent outcome
Swedberg K, et al. J Am Coll Cardiol. 2012; 59:1938-1945
www.shift-study.com