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S ystolic H eart failure treatment with the I f inhibitor ivabradine T rial. Objective, design and baseline. Swedberg K, et al. Eur J Heart Fail. 2010;12:75-81. www.shift-study.com. Swedberg K, et al. Lancet . 2010;376(9744):875-885. Primary objective. - PowerPoint PPT Presentation
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www.shift-study.com
Systolic Heart failure treatment with
the If inhibitor ivabradine Trial
Objective, design and baseline
www.shift-study.comSwedberg K, et al. Eur J Heart Fail. 2010;12:75-81Swedberg K, et al. Lancet. 2010;376(9744):875-885
www.shift-study.com
Primary objective
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 in sinus rhythm
4. Best recommended therapy
Swedberg K, et al. Eur J Heart Fail. 2010;12:75-81 www.shift-study.com
www.shift-study.com
Study organisation
Steering Committee
Argentina: S. Perrone Australia: H. KrumBelgium: W. Van MieghemBrazil: E. BocchiBulgaria: T. KatovaCanada: P. LiuChile: J. JalilChina: D. HuCzech Republic: J. VitovecDenmark: L. KøberEstonia: T. UuetoaFinland: M. NiemeläFrance: G. Jondeau
Germany: K. WerdanGreece: D. KremastinosHong-Kong: C. YuHungary: K. TóthIndia: D. S. RaoIreland: K. Mc DonaldItaly: M. MetraLatvia: J. Jirgenson†
A. ErglisLithuania: A. KavoliunieneMalaysia: K. SimThe Netherlands: A. Voors
Norway: K. DicksteinPoland: G. OpolskiPortugal: L. ProvidênciaRomania: D. IonescuRussia: G. Aroutiounov Slovakia: R. HatalaSlovenia: M. SebestjenSouth Korea: B. OhSpain: F. AvilésSweden: R. WillenheimerTurkey: A. OtoUnited Kingdom: M. CowieUkraine: O. Parkhomenko
Executive CommitteeM. Komajda co-chair, K. Swedberg co-chair
M. Böhm, J. Borer, I. Ford, L. Tavazzi
www.shift-study.com
EuropeAustriaBelgiumBulgaria DenmarkFinland France
Czech RepublicEstoniaHungary
South AmericaArgentinaBrazilChili
North AmericaCanada
AsiaChinaHong KongIndiaSouth KoreaMalaysia
Australia
LatviaLithuaniaNorwayPolandRomania
RussiaSlovakiaSloveniaUkraine
A landmark trial in heart failure
6505 patients, 37 countries, 677 centres
Germany Greece Ireland Italy The Netherlands
PortugalSpainSwedenTurkeyUK
www.shift-study.com
18 years
Class II to IV NYHA heart failure
Ischaemic/non-ischaemic aetiology
LV systolic dysfunction (EF 35%)
Heart rate 70 bpm
Sinus rhythm
Documented hospital admission for worsening heart failure 12 months
Inclusion criteria
Swedberg K, et al. Eur J Heart Fail. 2010;12:75-81
www.shift-study.com
Study design
HR and tolerabilityIvabradine 5 mg bid
Matching placebo, bid
Every 4 monthsD0 D14 D28 M4
Ivabradine 7.5/5/2.5 mg bid according to
3.5 years
Screening 7 to 30 days
Swedberg K, et al. Eur J Heart Fail. 2010;12:75-81
www.shift-study.com
Study endpoints
Cardiovascular death Hospitalization for worsening heart failure
Primary composite endpoint
Other endpoints
All-cause / CV / HF death All-cause / CV / HF hospitalization Composite of CV death, hospitalization for HF or non-fatal MI NYHA class / Patient & Physician Global Assessment
In total population and in patients with at least 50% target dose of beta-blockers
Swedberg K, et al. Eur J Heart Fail. 2010;12:75-81
www.shift-study.com
Patients and follow-up
Median study duration: 22.9 months; maximum: 41.7 months
6558 randomized
3268 to ivabradine 3290 to placebo
3264 analysed1 lost to follow-up
3241 analysed2 lost to follow-up
7411 screened
Excluded: 27 Excluded: 26
Swedberg K, et al. Lancet. 2010;376(9744):875-885
www.shift-study.com
Baseline characteristics
Ivabradine3241
Placebo3264
Mean age, y 60.7 60.1
Male, % 76 77
Ischaemic aetiology, % 68 67
NYHA II, % 49 49
NYHA III/IV, % 51 51
Previous MI, % 56 56
Diabetes, % 30 31
Hypertension, % 67 66
Swedberg K, et al. Lancet. 2010;376(9744):875-885
www.shift-study.com
Baseline characteristics
Ivabradine3241
Placebo3264
Mean heart rate, bpm 80 80
Mean LVEF, % 29 29
Mean SBP, mm Hg 122 121
Mean DBP, mm Hg 76 76
eGFR, mL/min/1.73 m2 75 75
Swedberg K, et al. Lancet. 2010;376(9744):875-885
www.shift-study.com
Chronic HF background treatment
89 9184
61
22
3
90 91
83
59
22
40
10
20
30
40
50
60
70
80
90
100
Beta-blockers ACEIs and/orARBs
Diuretics Aldosterone antagonists
Digitalis ICD/CRT
Patients (%)Ivabradine
Placebo
Swedberg K, et al. Lancet. 2010;376(9744):875-885
www.shift-study.com
0
10
20
30
40
50
60
70
80
90
100
BB at
randomization
At least 50%
target daily dose
Target daily dose
89
56
26
89
56
26
Patients (%)
Background beta-blocker treatment
Swedberg K, et al. Lancet. 2010;376(9744):875-885
Ivabradine
Placebo
www.shift-study.com
Main reasons for not achieving beta-blocker target dose, %
Ivabradinen=2099
Placebon=2126
Hypotension 44 45
Fatigue 32 32
Dyspnea 14 14
Dizziness 13 12
Bradycardia 6 6
Main reasons for not prescribing beta-blocker, %
Ivabradinen=344
Placebon=341
COPD 37 32
Hypotension 17 20
Asthma 10 11
Cardiac decomp. 7 9
Fatigue 5 6
Background beta-blocker treatment
Swedberg K, et al. Lancet. 2010;376(9744):875-885
