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

Bhm 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

Bhm 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

Bhm 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

-Blockers, % 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

Bhm 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

Hazard ratio=0.76
Patients with primary composite end point (%)

P<0.0001
40
Placebo

30

Ivabradine
20

10

0
0 6 12 18 24 30
Time (months)

Bhm 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
P=0.0166
Patients with cardiovascular death (%)

Placebo
20

10
Ivabradine

0
0 6 12 18 24 30
Time (months)

Bhm 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
Placebo
30
P<0.0001
Patients with cardiovascular death (%)

20

Ivabradine

10

0 6 12 18 24 30
Time (months)

Bhm 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
Hazard P
95% CI
ratio

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 1.00 1.20

Favors ivabradine Favors placebo

Bhm 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 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)

Bhm 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
30 -10 to <0 bpm
< -10 bpm

20

10

0
0 Day 28 6 12 18 24
Time (months)

Bhm 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

Bhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22 www.shift-study.com