1. analysis from the SHIFT study
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

2. 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

3. Baseline characteristics
Ivabradine
n=2052
Placebo
n=2098
Mean age, years 60
Male, % 77
BMI, kg/m2 28
Mean HF duration, years
3.4
HF ischemic cause, % 66 65
NYHA class III, % 50 51
NYHA class IV, % 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

4. Baseline background treatment
Ivabradine
n=2052
Placebo
n=2098
β-Blockers, % 87 88
At least half target dose 55 56
At target dose 26
ACE inhibitors/ARBs, % 90
Diuretics (excludes AAs), % 85 83
Aldosterone antagonists, % 63 61
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22

5. Effect of ivabradine on primary outcome
CV death or hospitalization for HF 6 12 18 24 30 40 10
Hazard ratio=0.76
P<0.0001
Patients with primary composite end point (%)
Time (months) 20
Placebo
Ivabradine
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22

6. on cardiovascular death
Effect of ivabradine
on cardiovascular death
Hazard ratio=0.83
P=0.0166 6 12 18 24 30 10 20
Time (months)
Placebo
Patients with cardiovascular death (%)
Ivabradine
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22

7. Effect of ivabradine on hospital admission for worsening heart failure
Hazard ratio=0.70
P<0.0001
Placebo 30 20
Ivabradine
Patients with cardiovascular death (%) 10 6 12 18 24 30
Time (months)
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22

8. Effect of ivabradine on major outcomes
1.00
Primary composite end point
Cardiovascular mortality
Hospitalization for worsening HF
Death from HF
All-cause mortality
All-cause hospitalization
Any cardiovascular hospitalization
0.20
<0.0001
0.0166
0.0006
0.0109 P
Hazard
ratio
1.20
0.40
0.60
0.80
95% CI
Favors ivabradine
Favors placebo
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22

9. Effect of ivabradine on outcomes according to HR achieved at 28 days6 12 18 24 40 10
Time (months) 20 30
Patients with primary composite end point (%)
Day 28
 75 bpm
70 to <75 bpm
65 to <70 bpm
60 to <65 bpm
<60 bpm
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22

10. Effect of ivabradine on outcomes
Patients with primary composite end point (%)
Effect of ivabradine on outcomes
according to magnitude of HR reduction 40
 0 bpm
-10 to <0 bpm
< -10 bpm 30 20 10
Day 28 6 12 18 24
Time (months)
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22

11. 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