Systolic Heart failure treatment with
the If inhibitor ivabradine Trial
Heart rate at baseline influences the effect
of ivabradine on cardiovascular outcomes
in chronic heart failure:
analysis from the SHIFT study
Effect of ivabradine on outcomes in patients with chronic heart failure and HR 75 bpm
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Aim
To assess the effect of ivabradine on outcomes
in heart failure patients on recommended
background therapies with heart rates ≥75 bpm
in the SHIFT trial
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Baseline characteristics
Ivabradine
Placebo
n=2052
n=2098
Mean age, years
60
60
Male, %
77
77
BMI, kg/m2
28
28
Mean HF duration, years
3.4
3.4
HF ischemic cause, %
66
65
NYHA class III, %
50
51
NYHA class IV, %
2
2
Mean LVEF, %
28.7
28.5
Mean HR, bpm
84.3
84.6
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Baseline background treatment
Ivabradine
Placebo
n=2052
n=2098
87
88
At least half target dose
55
56
At target dose
26
26
ACE inhibitors/ARBs, %
90
90
Diuretics (excludes AAs), %
85
83
Aldosterone antagonists, %
63
61
β-Blockers, %
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Effect of ivabradine on primary outcome
CV death or hospitalization for HF
Patients with primary composite end point (%)
Hazard ratio=0.76
P<0.0001
40
Placebo
30
Ivabradine
20
10
0
0
6
12
18
24
30
Time (months)
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Effect of ivabradine
on cardiovascular death
Hazard ratio=0.83
30
Patients with cardiovascular death (%)
P=0.0166
Placebo
20
Ivabradine
10
0
0
6
12
18
24
30
Time (months)
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Effect of ivabradine on hospital
admission for worsening heart failure
Hazard ratio=0.70
Patients with cardiovascular death (%)
30
Placebo
P<0.0001
20
Ivabradine
10
0
0
6
12
18
24
30
Time (months)
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Effect of ivabradine on major
outcomes
P
Hazard
ratio
95% CI
Primary composite end point
0.76
0.68-0.85
<0.0001
Cardiovascular mortality
0.83
0.71-0.97
0.0166
Hospitalization for worsening HF
0.70
0.61-0.80
<0.0001
Death from HF
0.61
0.46-0.81
0.0006
All-cause mortality
0.83
0.72-0.96
0.0109
All-cause hospitalization
0.82
0.75-0.90
<0.0001
Any cardiovascular hospitalization
0.79
0.71-0.88
<0.0001
0.20
0.40
0.60
0.80
Favors ivabradine
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
1.00
1.20
Favors placebo
www.shift-study.com
Effect of ivabradine on outcomes
according to HR achieved at 28 days
Patients with primary composite end point (%)
40
 75 bpm
30
70 to <75 bpm
65 to <70 bpm
60 to <65 bpm
20
<60 bpm
10
0
0 Day 28
6
12
18
24
Time (months)
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Effect of ivabradine on outcomes
according to magnitude of HR reduction
Patients with primary composite end point (%)
40
 0 bpm
-10 to <0 bpm
30
< -10 bpm
20
10
0
0 Day 28
6
12
18
24
Time (months)
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Conclusions
 In HF in sinus rhythm with HR ≥75 bpm heart rate reduction
with ivabradine improves outcomes, including all-cause
death and cardiovascular death reduces
 Ivabradine-associated risk reductions are related to both
HR achieved and magnitude of HR reduction
 Patients achieving <60 bpm or with >10 bpm reduction
have the best prognosis
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com