Transcript Hot topics from the Heart failure Congress in Sweden

Hot topics from the
Heart Failure Congress
in Belgrade
May 23rd, 2012
Our presenters today
Prof M. Komajda
Co-chairman of the SHIFT Executive Committee
Head of the Cardiovascular Department
Pitié-Salpêtrière Hospital
Paris, FRANCE
Prof S. Anker
Professor of cardiology: Division of Applied Cachexia Research
Department of cardiology,
Charité Campus Virchow-Klinikum
Berlin, Germany
The program
The new 2012 ESC Guidelines
10’
for heart failure
New evidence from the SHIFT
trial (Late Breaking Session) 10’
Questions and answers
15’
The new 2012 ESC
Guidelines for management
of heart failure
Prof S. Anker
The new 2012 ESC Guidelines for acute
and chronic heart failure
• 26 Task Force Members
• Avaivable online www.escardio.org
The principal changes from the 2008
guidelines
1. An expansion of the indication for mineralocorticoid
receptor antagonists (MRAs)
2. A new indication for the sinus node inhibitor ivabradine
3. An expanded indication for cardiac resynchronization
therapy (CRT)
4. New information on the role of coronary
revascularization in HF
5. Recognition of the growing use of ventricular assist
devices
6. The emergence of transcatheter valve interventions
7. Addition of MR-proANP to biomarkers for HF diagnosis
Diagnostic flowchart for patients with
suspected heart failure—showing
alternative ‘echocardiography first’ (blue)
or ‘natriuretic peptide first’ (red)
approaches.
Pharmacological therapy for CHF patients
Update on pharmacological therapy:
expansion of the indication for MRA
Update on pharmacological therapy: a new
indication for ivabradine for patients with CHF
Further treatment options for patients with
CHF
Update on implanted devices: an expanded
indication for CRT
New information on the role of coronary
revascularization in systolic HF
Lack of robust evidence for most lifestyle,
non-pharmacological interventions
RCT of “low” vs. “normal” sodium diet in systolic CHF
6 deaths
9 hospitalisations
15 deaths
30 hospitalisations
Lifestyle and non-pharmacological
interventions
Management programmes for patients
with heart failure
New evidence from the
trial
Presentations at Late Breaking Trials
and Rapid Fire sessions
Prof M. Komajda
Primary objective of the main trial
To evaluate whether the If inhibitor ivabradine
improves cardiovascular outcomes
in patients with
1. Moderate to severe chronic heart failure
2. Left ventricular ejection fraction 35%
3. Heart rate 70 bpm and in sinus rhythm
4. Recommended therapy
Main study results:
effect of ivabradine on major outcomes
Hazard ratio
p value
Primary composite endpoint
0.82
<0.0001
All cause mortality
0.90
0.092
Cardiovascular death
0.91
0.128
Death from HF
0.74
0.014
All-cause hospital admission
0.89
0.003
Hospitalization for HF
0.74
<0.0001
Any CV hospitalization
0.85
0.0002
CV death/hospitalization for HF
or non-fatal MI
0.82
<0.0001
0.5
Swedberg K, et al. Lancet 2010;376: 875-885.
0.6
0.7
0.8
0.9
1.0
1.1
Systolic Heart failure treatment with
the If inhibitor ivabradine Trial
New findings:
Ivabradine reduces mortality and other major
outcomes in chronic systolic heart failure: analysis
in high risk patients with HR ≥ 75 bpm
Presentation at Rapid Fire Session,
Sunday 20 May 2012
Rationale
 SHIFT and other heart failure studies showed a
continuous increase in risk with increasing heart rate
 64% of the patients enrolled in SHIFT had a heart rate ≥
75 bpm
 A cut-off of ≥75 bpm was chosen by the EMA for the
approval of ivabradine in chronic heart failure
Effect of ivabradine on major
outcomes in patients with HR 75 bpm
Hazard
ratio
P
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, et al. Clin Res Cardiol. Online 11 May 2012.
1.00
1.20
Favors placebo
Effect of ivabradine on outcomes
according to HR achieved at 28 days
Patients with primary composite end point (%)
40
 75 bpm
70 to <75 bpm
30
65 to <70 bpm
60 to <65 bpm
<60 bpm
20
10
0
0 Day 28
6
12
18
Time (months)
Böhm M, et al. Clin Res Cardiol. Online 11 May 2012.
24
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
Time (months)
Böhm M, et al. Clin Res Cardiol. Online 11 May 2012.
24
Available online now
Systolic Heart failure treatment with
the If inhibitor ivabradine Trial
New findings:
Heart rate reduction, not dose of beta-blocker, key
to ivabradine success in heart failure
Presentation at Late Breaking Trials,
Sunday 20 May 2012
Subgroups by beta-blocker dose
and heart rate
Five patient categories according to beta-blocker
status:
• No BB / <25 % / 25-49 / 50-74 / 75-99 / > 100 %
target dose
Five patient categories, according to baseline heart
rate:
• <72 bpm / 72 - 74 / 75 - 79 / 80 – 86 / ≥ 87 bpm
Swedberg K, et al. J Am Coll Cardiol 2012; 59:1938-1945
Clinical characteristics
No BB
BB <25%
BB 25% to <50%
BB 50% to <100%
BB ≥100%
Age, years
64
61
60
60
58
Resting HR, bpm
84
81
79
79
79
Systolic BP, mm Hg
121
117
120
122
125
LVEF, %
29
28
29
29
29
NYHA III or IV, %
58
54
49
50
51
COPD, %
33
11
11
9
5
Asthma, %
11
2
2
2
2
PAD, %
10
6
6
6
5
Hypertension, %
63
55
63
70
73
ACE/ARB, %
90
86
90
92
93
Diuretics, %
86
87
83
83
81
Swedberg K, et al. J Am Coll Cardiol 2012; 59:1938-1945
HR reduction according to
on beta-blocker and HR category
HR reduction from
baseline to 28 days
with ivabradine*
(bpm)
Baseline
HR category (bpm)
≥87
80 to <87
75 to <80
72 to <75
<72
No BB
BB<25%
BB 25-50% BB 50-100% BB ≥100%
Beta-blocker category
*Placebo corrected
No impact of BB dose
on HR reduction with ivabradine
Swedberg K, et al. J Am Coll Cardiol 2012; 59:1938-1945
Impact of baseline
HR on HR reduction
with ivabradine
Effect of ivabradine on outcomes
by beta-blocker doses
BB category
(% of target dose)
Placebo
event rate
(%)
Hazard
ratio
95 % CI
P
P
P
Heterogeneity
Trend
Trend adj**
PEP (CV death, HF hospitalisation)
39.3
0.71
0.55-0.93
40
0.74
0.59-0.92
BB (25 - 49)
30.8
0.81
0.68-0.98
BB (50 – 99)
24.8
0.88
0.72-1.07
BB (≥100)
20.1
0.99
0.79-1.24
No BB
29
0.62
0.45-0.85
BB (<25)
29
0.68
0.52-0.89
BB (25 – 49)
22
0.74
0.59-0.93
BB (50 - 99)
18
0.83
0.65-1.05
BB (≥100)
14
0.84
0.63-1.11
No BB
BB (<25)
0.35
0.056 0.135
HF hospitalisation
Swedberg K, et al. J Am Coll Cardiol 2012; 59:1938-1945
0.55
0.12
0.19
Available online now
Swedberg K, et al. J Am Coll Cardiol 2012; 59:1938-1945
Systolic Heart failure treatment with
the If inhibitor ivabradine Trial
New findings:
The effect of ivabradine on outcomes in patients
with or without aldosterone antagonists
Chronic HF background treatment
Patients (%)
100
90
89
90
91
91
84
Ivabradine
83
80
Placebo
70
61
59
60
50
40
30
22
22
20
10
3
4
0
Beta-blockers ACEIs and/or
ARBs
Swedberg K, et al. Lancet. 2010;376:875-885.
Diuretics
Aldosterone
antagonists
Digitalis
ICD/CRT
Type and dose of aldosterone
antagonists
3922 patients had aldosterone antagonist (AA)
at baseline:
•
•
•
Spironolactone: 3783 patients (mean dose = 34.7 mg)
Eplerenone: 100 patients (mean dose = 28.8 mg)
Other: 39 patients
Komajda et al. Late breaking trial. Heart Failure 2012
Baseline characteristics
With AA
Without AA
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 et al. Late breaking trial. Heart Failure 2012
P
Event rate in placebo group
Patients (%)
Patients with AA (n=1941)
50
Patients without AA (n=1323)
40
30
20
HR=1.40*
33
HR=1.35**
HR=1.40** HR=1.50*
23
19
18
13
10
23
17
11
HR=1.41***
6
0
Primary
endpoint
All-cause
mortality
P<0.0001; ** P=0.0004; *** P=0.0667
Komajda et al. Late breaking trial. Heart Failure 2012
CV death
3
Death
from HF
HF Hosp.
Effect of ivabradine on major
outcomes
Ivabradine
Primary endpoint (%)
With AA, n=3922
Without AA, n=2583
Placebo
Hazard
ratio*
P interaction
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 AA
Without AA
Hospitalization for HF (%)
With AA
Without AA
Death from any cause (%)
With AA
Without AA
Death from HF (%)
With AA
Without AA
0.4
Komajda et al. Late breaking trial. Heart Failure 2012
0.6
0.8
Favors ivabradine
1.0
1.2
1.4
Favors placebo
1.6
Conclusion
• The results of new analysis are consistent with the
main results of SHIFT, demonstrating that HR reduction
with ivabradine prevents adverse CV outcomes
• In patients with HR ≥75 bpm, ivabradine significantly
reduces all major outcomes, including all-cause death
and CV death
• The magnitude of the effect is similar in patients taking
or not aldosterone antagonists
• The magnitude of HR reduction with ivabradine, not the
dose of beta-blockers, determines improvement of
outcome
Ivabradine in the management of
systolic CHF: new ESC Guideline