i vabradine on recurrent hospitalization for worsening h eart failure findings from SHIFT S ystolic H eart failure treatment with the I f inhibitor ivabradine T rial ID: 308919
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Slide1
Effect of ivabradine on recurrent hospitalization for worsening heart failure: findings from SHIFT
S
ystolic
Heart failure treatment withthe If inhibitor ivabradine Trial
Borer JS, Böhm M, Ford I, et al. Eur Heart J. 2012;33(22):2813-2820
www.shift-study.comSlide2
Randomized, double-blind, placebo-controlled trial in 6505 patients to test the hypothesis that heart rate slowing with the If inhibitor ivabradine improves cardiovascular outcomes in patients with:Moderate to severe chronic heart failure (HF)Hospitalization for worsening HF within the 12 months prior to randomizationLeft
ventricular ejection fraction 35%Sinus rhythm and heart rate 70
bpm Receiving guidelines-based background HF therapy
Trial design
Swedberg
K, et al.
Lancet.
2010;376:875-885
www.shift-study.comSlide3
0
6
12
18
24
30
Months
40
30
20
10
0
Primary endpoint: composite of CV
death
or
hospitalization
for
heart
failure
- 18%
Cumulative
frequency
(%)
Placebo
Ivabradine
HR
(95% CI),
0.82
(0.75–0.90
)
P
<0.0001
Swedberg
K, et al.
Lancet.
2010;376:875-885
www.shift-study.comSlide4
0
6
12
18
24
30
Months
30
20
10
0
Secondary pre-specified endpoint:
hospitalization for heart failure
- 26%
Hospitalization
for HF (%)
Placebo
Ivabradine
HR
(95% CI),
0.74
(0.66;0.83
)
P
<0.0001
Swedberg
K, et al.
Lancet.
2010;376:875-885
www.shift-study.comSlide5
Objective of the current analysisTo assess the effect of heart rate slowing with ivabradine on recurrent hospitalizations for worsening heart failure
Borer JS, Böhm M, Ford I, et al. Eur Heart
J. 2012;33(22):2813-2820
www.shift-study.comSlide6
Predominant reason for hospital admissions in patients with HF = worsening HFHigh readmission rate after initial hospitalization:20% within one month50% within six months17% are readmitted two or more times
Hospitalization = the major contributor to the cost of HF care
Centers for Medicare and Medicaid Services. 2000 MedPAR data. DRG 127; Fonarow, GC. Rev Cardiovasc
Med. 2002;3 (suppl 4):S3; Krumholz HM et al. R Arch Intern Med. 1997 Jan 13;157(1):99-104; Roger VL, Circulation. 2012;125(1):e2-e220.Rationale: HF hospitalization burdenwww.shift-study.comSlide7
Economic burden of chronic HFHospitalization
accounts for most
CHF-associated
costsStewart S, et al. Eur J Heart Fail. 2002;4:361-71 Primary CareOutpatient referral
Drug treatmentPost-discharge
o
utpatient
visits
Hospital
admissions
www.shift-study.comSlide8
Analysis planEffect of ivabradine on
total hospitalizations: incidence rate ratio vs placebo
repeated hospitalizations: total-time
approach (time from randomization to 1st, 2nd and 3rd hospitalization)gap-time approach (time from 1st to 2nd hospitalization)All approaches adjusted for protocol-specified prognostic factors present pre-randomization (beta-blocker intake, NYHA class, ischaemic cause of HF, LVEF, age, SBP, HR, creatinine clearance)Borer JS, Böhm M, Ford I, et al.
Eur Heart J.
2012;33(22):
2813-2820
www.shift-study.comSlide9
Pre-randomization characteristics
Number of hospitalizations for HF during trial
None
(n=5319)
One
(n=714)
Two
(n=254)
Three
or >
(n=218)
P-
value
Age
(years)
60.0
62.3
61.8
62.4
<0.0001
Male
(%)
77
74
77
81
0.18
Heart rate
(
bpm
)
79.382.2
83.482.2<0.0001
SBP (mmHg)122.3119.8
118.1117.6<0.0001DBP (mmHg)76.075.073.4
73.3<0.0001LVEF (%)29.327.627.8
27.1<0.0001
NYHA class II (%)51
3838
34<0.0001
NYHA class III/IV (%)49
626266
Duration of HF
(years)
3.3
4.2
4.3
4.6
<0.0001
Diabetes
(%)
29
35
35
40
<0.0001
Borer JS, Böhm M, Ford I, et al.
Eur
Heart
J.
2012;33(22):
2813-2820
www.shift-study.comSlide10
Pre-randomization background treatment
Number of hospitalizations for HF during trial
None
(n=5319)
One
(n=714)
Two
(n=254)
Three
or >
(n=218)
P
-value
Beta-blockers
(%)
90
89
80
86
<0.0001
ACEI
and/or
ARB
(%)
91
89
90
93
0.13
MRA
(%)
58
696773
<0.0001 Diuretics (%)
82909095<0.0001 Digitalis (%)20
303335<0.0001Borer JS, Böhm M, Ford I, et al. Eur Heart J. 2012;33(22):
2813-2820www.shift-study.comSlide11
06
12
18
2430
Placebo
Ivabradine
40
10
0
IRR
(95% CI),
0.75
(0.65;0.87)
P=
0.0002
Cumulative incidence of HF
hospitalizations
(first and
repeated
)
Time (
months
)
20
30
-
25%
Effect of
ivabradine
on
total HF hospitalizations
Borer JS, Böhm M, Ford I, et al.
Eur
Heart
J. 2012;33(22):2813-2820www.shift-study.comSlide12
Effect of
ivabradine on recurrence of hospitalizations for HF
Total-time approach
1.2
0.8
0.6
1.0
0.4
Favours
ivabradine
Favours
placebo
First
hospitalization
Second
hospitalization
Third
hospitalization
Placebo
(n=3264)
Ivabradine
(n=3241)
Hazard
ratio
P
-value
P
<0.001P
<0.001P<0.012514 (16%)189 (6%)90 (3%)672 (21%)283 (9%)
128 (4%)0.750.660.71Borer JS, Böhm M, Ford I, et al.
Eur Heart J. 2012;33(22):2813-2820www.shift-study.comSlide13
Recurrences of HF hospitalizationsGap-time approach = effect on 2nd hospitalisationTime from 1st hospitalization to 2nd hospitalisation
Cumulative
frequency
(%)
Placebo
Ivabradine
HR
(95% CI),
0.84
(
0.69-1.01
)
P=
0.058
12
6
24
0
0
10
20
30
40
50
60
70
Time
from
first
hospitalization
(
months
)
472
patients
with
at
least
a
first and second
hospitalisation for
worsening
HF
Borer JS, Böhm M, Ford I, et al.
Eur
Heart
J.
2012;33(22):
2813-2820
www.shift-study.comSlide14
Total number of hospitalizations
Ivabradine (N=3241)
Placebo (N=3264)
IRR95% CI
p
-value
Hospitalization
for
worsening
HF
902
1211
0.75
0.65-0.87
0.0002
Hospitalization
for
any
cause
2661
3110
0.85
0.78-0.94
0.001
Cardiovascular
hospitalisation
1909
2272
0.84
0.76-0.94
0.002
Hospitalization
for other than
worsening of HF17591899
0.920.83-1.02
0.12Borer JS, Böhm M, Ford I, et al. Eur Heart J. 2012;33(22):2813-2820www.shift-study.comSlide15
LimitationsBoth of the statistical models have well known limitationstotal-time approach: treatment effect dependent on previous hospitalizations
(cumulative effect)gap-time approach: restricted set of patients; therefore, randomization
not preservedData on hospitalization burden
may be influenced by differences between health care systems in different countries Borer JS, Böhm M, Ford I, et al. Eur Heart J. 2012;33(22):2813-2820www.shift-study.comSlide16
Heart rate reduction with ivabradine in patients with chronic HF, in sinus rhythm, with heart rate ≥70 bpm and already receiving guidelines-suggested therapies substantially decreases the risk of clinical deterioration as reflected by:reduction in the total hospitalizations for worsening HFreduction in the incidence of recurrent HF hospitalizationsincrease in time to first and subsequent
hospitalizations This benefit
reduces the total burden of HF for the patient and can be expected to substantially reduce health care costs
ConclusionBorer JS, Böhm M, Ford I, et al. Eur Heart
J. 2012;33(22):2813-2820
www.shift-study.com