Transcript Tardif SHIFT Echocardiography Substudy

Systolic Heart failure treatment with
the If inhibitor ivabradine Trial
Influence of background treatment with
mineralocorticoid receptor antagonists on
ivabradine's effects in patients with chronic
heart failure
Komajda M, Böhm M, Borer J et al. Eur J Heart Fail. 2013;15(1):79-84
www.shift-study.com
Objective
To explore whether ivabradine is beneficial in patients with
systolic HF, in sinus rhythm, with resting HR ≥70 bpm, and
whose guideline-recommended background therapy includes
mineralocorticoid receptor antagonist
Komajda M, Böhm M, Borer J, et al. Eur J Heart Fail. 2013;15(1):79-84
www.shift-study.com
Statistical method
Effect of ivabradine was assessed
• separately in patients with and without MRA at baseline
• using a time-to-first-event survival analysis (a Cox’s proportional
hazards model including treatment effect and adjusted for
prognostic factors at baseline such as BB intake, HR, NYHA
class, LVEF, ischaemic cause of HF, age, SBP, EGFR)
• p value for interaction between treatment and presence or not of
MRA was provided by adding this interaction to the Cox model
Komajda M, Böhm M, Borer J, et al. Eur J Heart Fail. 2013;15(1):79-84
www.shift-study.com
Baseline characteristics
With MRA
Without MRA
n=3922
n=2583
Mean age, years
59
62
<0.0001
Male, %
76
78
Mean BMI, kg/m2
28
28
0.0782
0.0013
Mean HF duration, years
3
4
0.0551
HF ischemic cause, %
63
76
<0.0001
NYHA class II, %
45
54
<0.0001
NYHA class III, %
53
45
Mean LVEF, %
28
30
<0.0001
Mean HR, bpm
80
79
<0.0001
Mean systolic BP, mm Hg
119
126
<0.0001
Mean diastolic BP, mm Hg
75
77
<0.0001
Komajda M, Böhm M, Borer J, et al. Eur J Heart Fail. 2013;15(1):79-84
P
www.shift-study.com
Baseline background treatment
With MRA
Without MRA
n=3922
n=2583
β-Blocker, %
90
89
0.2477
ACE inhibitor/ARB, %
91
91
0.7292
Diuretic (excludes AA), %
88
76
<0.0001
Digitalis, %
28
13
<0.0001
Komajda M, Böhm M, Borer J, et al. Eur J Heart Fail. 2013;15(1):79-84
P
www.shift-study.com
Effect of ivabradine on heart rate
Mean HR, bpm
Patients with MRA
Mean change in HR, bpm
Baseline
M1-baseline
M12-baseline
80.0  9.5
-15.4 10.7
-14.3 12.4
79.3  9.4
-15.3 10.8
-14.3 11.7
n=1981
Patients without MRA
n=1260
Komajda M, Böhm M, Borer J, et al. Eur J Heart Fail. 2013;15(1):79-84
www.shift-study.com
Effect of ivabradine on major
outcomes
Ivabradine Placebo
Hazard ratio*
p interaction
Primary endpoint
With MRA, n=3922
Without MRA, n=2583
28%
19%
33%
23%
0.82
0.81
0.916
16%
11%
18%
11%
0.88
1.02
0.279
19%
11%
23%
17%
0.77
0.67
0.304
17%
13%
19%
13%
0.88
0.99
0.366
4%
3%
6%
3%
0.73
0.80
0.723
Cardiovascular death
With MRA, n=3922
Without MRA, n=2583
Hospitalization for HF
With MRA, n=3922
Without MRA, n=2583
Death from any cause
With MRA, n=3922
Without MRA, n=2583
Death from heart failure
With MRA, n=3922
Without MRA, n=2583
* adjusted for prognostic factors at baseline
0.4
0.6
0.8
Favors ivabradine
Komajda M, Böhm M, Borer J, et al. Eur J Heart Fail. 2013;15(1):79-84
1.0
1.2
1.4
1.6
Favors placebo
www.shift-study.com
Safety
Ivabradine
Placebo
Ivabradine
Placebo
n=1977
n=1938
n=1255
n=1322
Serious adverse events, %
44*
48
40
42
Adverse events leading to
withdrawal, %
15
14
13
11
Emergent adverse events, %
75
75
75
72
4*
5*
9
1
2
3*
<1
1
7
2
2
<1
5*
6*
8
<1*
1*
3*
1
1
6
2
3
<1
Selected adverse events, %
•
•
•
•
•
•
Sym/ bradycardia
Asym/ bradycardia
Atrial fibrillation
Hyperkalemia
Renal failure
Phosphenes
* Differences is significant
Komajda M, Böhm M, Borer J, et al. Eur J Heart Fail. 2013;15(1):79-84
www.shift-study.com
Conclusion
 Ivabradine improves outcomes in the SHIFT population
receiving or not aldosterone antagonists and the magnitude of
the improvement is similar in the two groups
 The addition of ivabradine should be considered in patients
with heart failure with reduced LVEF, sinus rhythm and heart
rate of 70 bpm or higher, whatever their background
neurohormonal treatment
Komajda M, Böhm M, Borer J, et al. Eur J Heart Fail. 2013;15(1):79-84
www.shift-study.com