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
www.shift-study.com Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
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
www.shift-study.com Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
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
www.shift-study.com Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
968 patients
ivabradine
976 patients
placebo
161 excluded
KCCQ assessed in 1944 patients
177 excluded
2282 patients from24 countries with a validated
KCCQ
Substudy population
Median study duration: 24.5 months; maximum: 29.3 months
www.shift-study.com Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
Baseline characteristics
Ivabradinen=968
Placebon=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
www.shift-study.com Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
Baseline background treatment
Ivabradinen=968
Placebon=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
www.shift-study.com Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
Baseline characteristics by low, medium and higher KCCQ
OSS <50
n=455
OSS 50 to <75
n=807
OSS ≥75
n=682P-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
www.shift-study.com Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
Incidence (%)
Time (months)
≥75
50-<75
<50
Incidence of the primary endpoint by class of KCCQ overall score in
Placebo group (n=976)
P <0.001
www.shift-study.com Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
Time (months)
<50
50-<75
≥75
Incidence of worsening HF by class of KCCQ overall score in
Placebo group (n=976)
P <0.001
Incidence (%)
www.shift-study.com Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
= 2.4, P <0.001
Overall summary scoreChange from baseline – 12 months
69.6
65.3
71.9
65.2
Ivabradine (n=842)
Baseline M12
Placebo (n=839)
Baseline M1255
70
75
60
65
6.7 4.3 KCCQ OSS
www.shift-study.com Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
Clinical summary scoreChange from baseline – 12 Months
= 1.8, P=0.018
72.3
69
74.1
69.1
Ivabradine (n=842)
Baseline M12
Placebo (n=839)
Baseline M1260
70
75
65
5.0 3.3 KCCQ CSS
www.shift-study.com Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
P =<0.001
Mean of change KCCQ Overall Summary Score at 12 months
by quintiles of HR change
www.shift-study.com Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
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.
www.shift-study.com Ekman I, Chassany O, Komajda M, et al. Eur Heart J. 2011;32(19):2395-404
