10 Jahre Levosimendan bei akuter und chronischer Herzinsuffizienz

16 Pages·2013·3.19 MB·English

by  Georg Delle Karth

19.04.13
10
 Jahre
 Levosimendan
 bei
 akuter
 und
 chronischer

Herzinsuffizienz
 in
 Österreich:
 Was
 haben
 wir

gelernt,
 wo
 stehen
 wir,
 was
 bringt
 die
 ZukunA

georg.delle-­‐[email protected]

Akut
 dekompensiertes
 Herzversagen:
 Therapie

100 92,9
80
nt 60
e
c
Per 40 36,5 27,2
20 13,9 10,1 16,3
0
ASB-CPADPiuretikaBeta-BlocOkpeiroideIV-NitrateIV Inotropika
Nieminen et. al: EuroHeart Failure Survey II; European Heart Journal, 2006Nov;27:2725-36
Akut
 dekompensiertes
 Herzversagen:
 Inotrope

Therapie

Adrenalin
9% 6% Dobutamin
Dopamin
13% Levosimendan
Noradrenalin
34%
38%
Nieminen et. al: EuroHeart Failure Survey II; European Heart Journal, 2006Nov;27:2725-36
1
19.04.13
IV
 inotropes
 used
 in
 31%
 of
 AHF
 paNents
 with
 iniNal

SBP>=100mmHg
 compared
 to
 72%
 use
 in
 paNents
 <100mmHg

100%
91%
90% 86%
80% 72%
70%
60%
50% 47%
40%
31%
30% 27%
20%
10% 9% 6%
0%
<100 mmHg (20% AHF) >100 mmHg (80% AHF)
IV Diuretics IV vasodilators IV inotropes SIMDAX
ALARM-HF : Sample =All AHF patients with specified initial SBP 5,009
Follath F et al. Intensive Care Med. 2011;37:619-26
Mortality
 in
 paNents
 with
 iniNal
 SBP
 >=
 100
 vs
 <100mmHg:

ADCHF
 vs
 De
 Novo
 AHF
 (cardiogenic
 shock
 excluded)

20%
16%
15%
14%
10%
6% 6%
5%
0%
All AHF AdCHF De Novo
Patient died (SBP >=100) Patient died (SBP <100)
ALARM-HF: 951(19%) patients with initial SBP < 100mmHg (648 ADCHF, 303 De Novo AHF)
Follath F et al. Intensive Care Med. 2011;37:619-26
2
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0.05µg/kg/min
Levosimendan
OR-1896
OR-1855
0.1 µg/kg/min
J Clin Pharmacol 2002;42:43-51
Hämodynamische
 Effekte

Levosimendan

acute hemodynamic effects in pts with CHF
CI SVR
SV
PCWP
Slawsky et al. Circulation 2000;102:2222-27
3
19.04.13
Inotropie
 –
 auch
 bei
 Stunning?

Intracoronary Levosimendan enhances
Contractile Function of Stunned Myocardium
•  anästhesierte Hunde, n=9
•  5x5 min Perioden LAD Occlusion/ Reperfusion
•  3 h Reperfusion
•  Levosimendan 1.5 - 12µg/min über 10min
•  Ultrasonic segment length transducers
Anesth Analg 1997;85:23-9
Intracoronary Levosimendan enhances
Contractile Function of Stunned Myocardium
LAD Region
* p<0.05 vs 3h Reperfusion
+ p<0.05 vs 1.5µg/min Levo
++ p<0.05 vs 3µg/min Levo
§ p<0.05 vs drug vehicle
Anesth Analg 1997;85:23-9
4
19.04.13
Levosimendan
 Improves
 Stunned
 Myocardium

•  24
 PaNenten
 mit
 PCI
 bei
 ACS
 (23
 STEMI)

•  Alle
 PaNenten
 TIMI
 III
 Fluss

•  Doppelblind
 24µg/kg
 Levosimendan
 gegen
 Placebo
 (2:1)

•  Ventrikulographie,
 PAC;

 Baseline
 -­‐
 20‘

Sonntag et al; JACC 2004 43, 2177-2182
Levosimendan
 Improves
 Stunned
 Myocardium

No
 of
 hypokineNc
 segments

P = 0.015
9
8
s 7
ber 6
m 5
u Levo
n 4 Placebo
3
2
1
0
Baseline 20'
Sonntag et al; JACC 2004 43, 2177-2182
Levosimendan
 and
 Coronary
 Hemodynamics

•  10
 Pat.
 mit
 KHK
 bei
 geplanter
 HK-­‐Untersuchung

•  Links-­‐,
 Rechts-­‐
 HK,
 TTE,
 BlutgasbesNmmung
 aus

Koronarsinus

•  Doppler
 Guidwire
 (FloWire)

•  Levosimendan
 24-­‐µg/kg
 IV

•  Messung:
 Baseline-­‐15-­‐30
 Minuten

Michaels et al. Circulation 2005;111:1504-1509
5
19.04.13
Levosimendan
 and
 Coronary
 Hemodynamics

P = 0.04
P = 0.04
Michaels et al. Circulation 2005;111:1504-1509
Levosimendan
 und
 diastolische
 FunkNon

Effects
 of
 Levosimendan
 on
 leA
 ventricular
 relaxaNon
 and
 early

filling
 at
 maintained
 preload
 and
 aAerload
 condiNons
 aAer

AorNc
 Valve
 Replacemet
 for
 AorNc
 stenosis

Jörgenensen et al. Circulation. 2008;117:1075-1081
6
19.04.13
Unterschied
 zu
 anderen
 Inotropika

Myocardial
 Infarct
 Size
 in
 Dogs

Dogs with 60 min LAD Occlusion
e, 60 *cPo<n0tr.0o5l acnodm wpiatrheLde vwoit+hG lyburide
Sizk 50
yocardial Infarct % of area at ris 432000 24 ± 2 * 11 ± 2 24 ± 4 28 ± 4
M 10
0
Control Levo Levo Glyburide
(n = 8) (n = 9) + Glyburide (n = 10)
(n = 10)
Kersten JR et al. Anesth Analg 2000;90:5–11.
Levosimendan
 pre-­‐treatment
 improves
 outcomes
 in
 paNents

undergoing
 coronary
 artery
 bypass
 graA
 surgery

24 µg kg-1
Bolus
Tritapepe et al. Br J Anaesth 2009; 102: 198–204
7
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Levosimendan pre-treatment improves outcomes in patients
undergoing coronary artery bypass graft surgery

ICU LOS
16
p < 0.0001
12
s
our 8
h
4
0
Placebo Levo
Tritapepe et al. Br J Anaesth 2009; 102: 198–204
Levosimendan pre-treatment improves outcomes in patients
undergoing coronary artery bypass graft surgery
p < 0.0001
Tritapepe et al. Br J Anaesth 2009; 102: 198–204
Levosimendan pre-treatment improves outcomes in patients
undergoing coronary artery bypass graft surgery
p < 0.007
Tritapepe et al. Br J Anaesth 2009; 102: 198–204
8
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Klinische
 Daten

REVIVE
 II:
 MulNcenter
 Placebo-­‐Controlled
 Trial
 of
 Levosimendan
 on

Clinical
 Status
 in
 Acutely
 Decompensated
 Heart
 Failure

Packer M et al. Am Coll Cardiol HF 2013;1:103–11
REVIVE II: Multicenter Placebo-Controlled Trial of
Levosimendan on Clinical Status in Acutely
Decompensated Heart Failure

Primary Endpoint (6h + 24h + 5d)
70
60 Levosimendan
50 Placebo
% 40
30
20
10
p-value = 0.015
0
ImprovedUnchangeWdorse
Packer M et al. Am Coll Cardiol HF 2013;1:103–11
9
19.04.13
REVIVE II: Multicenter Placebo-Controlled Trial of
Levosimendan on Clinical Status in Acutely
Decompensated Heart Failure
BNP-­‐levels

 p
 <

 0.001

Packer M et al. Am Coll Cardiol HF 2013;1:103–11
REVIVE II: Multicenter Placebo-Controlled Trial of
Levosimendan on Clinical Status in Acutely
Decompensated Heart Failure
HR
 1.26
 (95%
 CI:
 0.83
 to
 1.91)
 ,
 p
 =
 0.29

Packer M et al. Am Coll Cardiol HF 2013;1:103–11
REVIVE II: Multicenter Placebo-Controlled Trial of
Levosimendan on Clinical Status in Acutely
Decompensated Heart Failure
Packer M et al. Am Coll Cardiol HF 2013;1:103–11
10