Systolic Heart failure treatment with
the If inhibitor ivabradine Trial
Heart rate reduction with ivabradine and
health related quality of life in patients with
chronic heart failure:
results from the SHIFT study
Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
www.shift-study.com
Aim of the HQoL substudy
To evaluate whether heart rate (HR) reduction
with ivabradine is associated with increased HQoL
in parallel to a reduction of primary outcomes in SHIFT
METHOD
Kansas City Cardiomyopathy Questionnaire (KCCQ)
was used at baseline, 4, 12, and 24 months after randomization
Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
www.shift-study.com
KCCQ
 Disease specific, 23 items, ranging from 0 to 100 (higher
score = better HQoL)
 physical limitation
 symptoms (frequency, burden)
 quality of life
 social interference
 self-efficacy
 Clinical Summary Score (CSS):
Mean of the physical limitation and total symptom
domains scores
 Overall Summary Score (OSS):
CCS + quality of life and social limitation scores
Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
www.shift-study.com
Substudy population
2282 patients from
24 countries with a validated
KCCQ
161 excluded
177 excluded
KCCQ assessed in 1944 patients
968 patients
ivabradine
976 patients
placebo
Median study duration: 24.5 months; maximum: 29.3 months
Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
www.shift-study.com
Baseline characteristics
Ivabradine
n=968
Placebo
n=976
Mean age, years
61
61
Male, %
75
77
BMI, kg/m2
28
28
Mean HF duration, years
4
4
HF ischaemic cause, %
65
63
NYHA class II, %
59
57
NYHA class III, %
40
42
NYHA class IV, %
1
1
Mean LVEF, %
28
28
Mean HR, bpm
80
80
Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
www.shift-study.com
Baseline background treatment
Ivabradine
n=968
Placebo
n=976
Beta-blocker, %
90
91
ACE inhibitor, %
81
83
ARB, %
16
15
Diuretics, %
85
83
Aldosterone antagonist, %
67
64
Digitalis, %
19
19
Devices, %
5
7
Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
www.shift-study.com
Baseline characteristics by low, medium
and higher KCCQ
OSS <50 OSS 50 to <75
n=455
n=807
OSS ≥75
n=682
P-value
Mean age, years
62
61
60
ns
Male, %
71
75
81
0.0008
BMI, kg/m2
29
28
28
ns
Mean HR, bpm
82
80
79
<0.0001
Systolic BP, mm Hg
121
122
121
ns
Diastolic BP, mm Hg
74
75
75
ns
Mean LVEF, %
28
28
28
ns
Mean eGFR, mL/min/1.73 m²
72
73
76
0.0007
NYHA class II, %
32
54
79
<0.0001
NYHA class III, %
64
45
20
NYHA class IV, %
4
0.5
0.3
Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
www.shift-study.com
Incidence of the primary endpoint by
class of KCCQ overall score in
Placebo group (n=976)
Incidence (%)
P <0.001
<50
50-<75
≥75
Time (months)
Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
www.shift-study.com
Incidence of worsening HF
by class of KCCQ overall score in
Placebo group (n=976)
Incidence (%)
P <0.001
<50
50-<75
≥75
Time (months)
Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
www.shift-study.com
Overall summary score
Change from baseline – 12 months
 = 2.4, P <0.001
KCCQ OSS
 6.7
75
 4.3
71.9
69.6
70
65.2
65.3
65
60
55
Baseline
M12
Ivabradine (n=842)
Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
Baseline
M12
Placebo (n=839)
www.shift-study.com
Clinical summary score
Change from baseline – 12 Months
 = 1.8, P=0.018
 5.0
KCCQ CSS
 3.3
74.1
75
72.3
70
69.1
69
65
60
Baseline
M12
Ivabradine (n=842)
Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
Baseline
M12
Placebo (n=839)
www.shift-study.com
Mean of change KCCQ
Overall Summary Score at 12 months
by quintiles of HR change
P =<0.001
Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
www.shift-study.com
Conclusions
In symptomatic patients with systolic heart failure and
elevated heart rate:
 Lower HQoL is associated with increased risk for
cardiovascular outcomes.
 Elevated heart rate at rest is associated with lower HQoL.
 Heart rate reduction with Ivabradine improves HQoL.
 The magnitude of HR reduction with Ivabradine is directly
related to the degree of improvement in HQoL.
Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
www.shift-study.com