Transcript PROCORALAN

Systolic Heart failure treatment with
the If inhibitor ivabradine Trial
Main results
Swedberg K, et al. Lancet. 2010;376(9744):875-885
www.shift-study.com
Primary composite endpoint
(CV death or hospital admission for worsening HF)
Cumulative frequency (%)
40
HR = 0.82 (0.75–0.90)
Placebo
P < 0.0001
18%
30
Ivabradine
20
10
0
0
6
12
18
24
30
Months
Swedberg K, et al. Lancet. 2010;376(9744):875-885
www.shift-study.com
Hospitalization for HF
Cumulative frequency (%)
30
Placebo
HR = 0.74 (0.66–0.83)
P < 0.0001
26%
20
Ivabradine
10
0
0
6
12
18
24
30
Months
Swedberg K, et al. Lancet. 2010;376(9744):875-885
www.shift-study.com
Death from heart failure
Cumulative frequency (%)
10
HR = 0.74 (0.58–0.94)
P = 0.014
Placebo
26%
5
Ivabradine
0
0
6
12
18
24
30
Months
Swedberg K, et al. Lancet. 2010;376(9744):875-885
www.shift-study.com
Effect of ivabradine
on outcomes
Endpoints
Hazard ratio
95% CI
p value
0.82
[0.75;0.90]
p<0.0001
All-cause mortality
0.90
[0.80;1.02]
p=0.092
Death from heart failure
0.74
[0.58;0.94]
p=0.014
All-cause hospital admission
0.89
[0.82;0.96]
p=0.003
Any CV hospital admission
0.85
[0.78;0.92]
p=0.0002
CV death/hospital admission for
HF or non-fatal MI
0.82
[0.74;0.89]
p<0.0001
Primary composite endpoint
(CV death or hospital admission for worsening HF)
Swedberg K, et al. Lancet. 2010;376(9744):875-885
www.shift-study.com
Effect of ivabradine in
prespecified subgroups
Test for interaction
Age
<65 years
≥65 years
Sex
Male
Female
Beta-blockers
No
Yes
Aetiology of heart failure
Non-ischaemic
Ischaemic
NYHA class
NYHA class II
NYHA class III or IV
Diabetes
No
Yes
Hypertension
No
Yes
Baseline heart rate
P = 0.029
<77 bpm
≥77 bpm
0.5
1.0
Hazard ratio
Favours ivabradine
Swedberg K, et al. Lancet. 2010;376(9744):875-885
1.5
Favours placebo
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Mean heart rate reduction
70% of patients on ivabradine 7.5 mg bid
Heart rate (bpm)
90
80
80
Placebo
75
75
70
67
64
60
Ivabradine
50
0
2 weeks
1
4
8
12
16
20
24
28
32
Months
Swedberg K, et al. Lancet. 2010;376(9744):875-885
www.shift-study.com
NYHA class changes
Patients (%)
68
70
70
P = 0.0003
60
Ivabradine
50
Placebo
40
30
28
24
20
5
10
6
0
Improvement
Swedberg K, et al. Lancet. 2010;376(9744):875-885
Stability
Worsening
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Incidence of selected adverse
events (n = 6492)
Patients with an event
Ivabradine
Placebo
N=3232, n (%)
N=3260, n (%)
All serious adverse events
1450 (45%)
1553 (48%)
0.025
All adverse events
2439 (75%)
2423 (74%)
0.303
Symptomatic bradycardia
150 (5%)
32 (1%)
<0.0001
Asymptomatic bradycardia
184 (6%)
48 (1%)
<0.0001
Atrial fibrillation
306 (9%)
251 (8%)
0.012
Phosphenes
89 (3%)
17 (1%)
<0.0001
Blurred vision
17 (1%)
7 (<1%)
0.042
Swedberg K, et al. Lancet. 2010;376(9744):875-885
p value
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Treatment discontinuation
Patients with an adverse event,
leading to withdrawal
Ivabradine
Placebo
N=3232, n (%)
N=3260, n (%)
467 (14%)
416 (13%)
0.051
Symptomatic bradycardia
20 (1%)
5 (<1%)
0.002
Asymptomatic bradycardia
28 (1%)
5 (<1%)
<0.0001
Atrial fibrillation
135 (4%)
113 (3%)
0.137
Phosphenes
7 (<1%)
3 (<1%)
0.224
Blurred vision
1 (<1%)
1 (<1%)
1.000
All adverse events
Swedberg K, et al. Lancet. 2010;376(9744):875-885
p value
www.shift-study.com
Conclusion
Ivabradine significantly reduces major risks associated
with heart failure:
 18% reduction in CV death or hospital admission for worsening HF
 26% reduction in death from heart failure
 26% reduction in hospital admission for worsening heart failure
Benefits are apparent early, are consistent in
predefined subgroups, and have been
demonstrated on top of recommended therapy
Treatment is well tolerated
Swedberg K, et al. Lancet. 2010;376(9744):875-885
www.shift-study.com