Fichier PDF

Partage, hébergement, conversion et archivage facile de documents au format PDF

Partager un fichier Mes fichiers Convertir un fichier Boite à outils PDF Recherche PDF Aide Contact



Changer l'IEC pour la Sacubritil ValsartanBauer Fabrice 2019 .pdf



Nom original: Changer l'IEC pour la Sacubritil-ValsartanBauer_Fabrice_2019.pdf
Titre: Changer l'IEC pour la Sacubritil-Valsartan
Auteur: Fabrice Bauer

Ce document au format PDF 1.4 a été généré par JESFC 2019 / iTextSharp 5.1.2 (c) 1T3XT BVBA, et a été envoyé sur fichier-pdf.fr le 30/01/2019 à 23:23, depuis l'adresse IP 105.99.x.x. La présente page de téléchargement du fichier a été vue 99 fois.
Taille du document: 2.2 Mo (28 pages).
Confidentialité: fichier public




Télécharger le fichier (PDF)









Aperçu du document


Heart failure with reduced ejection fraction: difficult situations

SWITCH ACE FOR SACUBRITIL VALSARTAN
PR BAUER

Disclosure Statement of Financial Interest
I currently have, or have had over the last two years, an affiliation or financial interests or interests of any order with a company
or I receive compensation or fees or research grants with a commercial company :

Speaker's name : Fabrice, BAUER

☑ Je n'ai pas de lien d'intérêt potentiel à déclarer

McMurray. Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure, NEJM 2014

Discussing Out-of-Pocket Costs With Patients: Shared
Decision Making for Sacubitril-Valsartan in Heart Failure

Smith GH. Discussing Out-of-Pocket Costs With Patients: Shared Decision Making for Sacubitril-Valsartan in Heart Failure. J Am Heart Assoc. 2019

Eligibility of sacubitril–valsartan in a real-world heart failure
population: a community-based single-centre study

40% eligible for SV COHORT A, EF < 40%

24% eligible for SV

COHORT B, EF < 35%

Norberg. Eligibility of sacubitril–valsartan in a real-world heart failure population: a community-based single-centre study ESC Heart Failure 2018

Eligibility of sacubitril–valsartan in a real-world heart failure
population: a community-based single-centre study

Eligible
24%

ACE/ARAi
not > 50%
34%

Contraindicated
6%

Eligible
40%

Blood pressure and eGFR

Not
indicated
20%
BNP

COHORT A, EF < 40%

Not BNP
indicated
12%

ACE/ARAi
not
optimal
61%
Contraindicated
Blood pressure and eGFR3%

COHORT B, EF < 35%

Norberg. Eligibility of sacubitril–valsartan in a real-world heart failure population: a community-based single-centre study ESC Heart Failure 2018

Candidate and patient phenotype in PARADIGM trial
64 yo

K < 5.2 mmol/l S and 5.4 mmol/l R

EF < 40% (35% 2010)
NYHA 2 72% ,3 23% (and 4 1%)

Full dose then 50%
of ACEi posology
Admitted (62%) or not for HF (38%) within
the 12 months prior to randomization

eGFR > 30 ml/min/1.73m²
but serum creatinin 99mol/l
SBP > 100 mm Hg S
and > 95 mm Hg R
Implantable cardioverter–
defibrillator 14% and CRT 7%

Candidate and patient phenotype in PARADIGM trial
64 yo

K < 5.2 mmol/l S and 5.4 mmol/l R

EF < 40% (35% 2010)
NYHA 2 72% ,3 23% (and 4 1%)

Full dose then 50%
of ACEi posology
Admitted (62%) or not for HF (38%) within
the 12 months prior to randomization

eGFR > 30 ml/min/1.73m²
but serum creatinin 99mol/l
SBP > 100 mm Hg S
and > 95 mm Hg R
Implantable cardioverter–
defibrillator 14% and CRT 7%

Rise your hand if you switch ACEi/A2RA to SV
1.
2.
3.
4.
5.

6.
7.

When eGFR is 33 ml/min/1.73 m² (Creatinin = 185 mol/l) ?
In patients with low blood pressure ?
In patients in NYHA functional class IV ?
In patients receiving full dose of ACEi/A2RA stabilized for a while ?
In patients fullfilling the PARADIGM inclusion criteria but having
significant functional MR complicated with pulmonary hyperension
and severe right ventricular dysfunction ?
In young patient fullfilling the PARADIGM inclusion ?
….

Rise your hand if you switch ACEi/A2RA to SV
1.
2.
3.
4.
5.

6.
7.

When eGFR is 33 ml/min/1.73 m² (Creatinin = 185 mol/l) ?
In patients with low blood pressure ?
In patients in NYHA functional class IV ?
In patients receiving full dose of ACEi/A2RA stabilized for a while ?
In patients fullfilling the PARADIGM inclusion criteria but having
significant functional MR complicated with pulmonary hyperension
and severe right ventricular dysfunction ?
In young patient fullfilling the PARADIGM inclusion ?
….

Haynes, Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney Disease. Circulation 2018

ENTRESTO IN CKF
UK HARP-III trial (United Kingdom Heart and
Renal Protection-III)



A randomized double-blind trial, included
414 participants



Estimated glomerular filtration rate (GFR) 20
to 60 mL/min/1.73) m2





< 30ml/min (38%)



30-45 ml/min (42%)



> 45 ml/min (24%)

Randomly assigned to




sacubitril/valsartan 97/103 mg twice daily
versus irbesartan 300 mg once daily.

Primary outcome was measured GFR at 12
months using ANCOVA with adjustment for
each individual’s baseline measured GFR.
All analyses were by intention to treat.

ENTRESTO IN CKF

Haynes, Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney
Disease. Circulation 2018

Rise your hand if you switch ACEi/A2RA to SV
1.
2.
3.
4.
5.

6.
7.

When eGFR is 33 ml/min/1.73 m² (Creatinin = 185 mol/l) ?
In patients with low blood pressure ?
In patients in NYHA functional class IV ?
In patients receiving full dose of ACEi/A2RA stabilized for a while ?
In patients fullfilling the PARADIGM inclusion criteria but significant
functional MR complicated with pulmonary hyperension and severe
right ventricular dysfunction ?
In young patient fullfilling the PARADIGM inclusion ?
….

1.23 per pt

1.36 per pt

Bohm, Systolic blood pressure, cardiovascular outcomes and efficacy and safety of sacubitril/valsartan (LCZ696) in patients with chronic heart failure and reduced
ejection fraction: results from PARADIGM-HF. EHJ 2017

ENTRESTO AND HYPOTENSION

Bohm, Systolic blood pressure, cardiovascular outcomes and efficacy and safety of sacubitril/valsartan (LCZ696) in patients with chronic heart failure and reduced
ejection fraction: results from PARADIGM-HF. EHJ 2017

Rise your hand if you switch ACEi/A2RA to SV
1.
2.
3.
4.
5.

6.
7.

When eGFR is 33 ml/min/1.73 m² (Creatinin = 185 mol/l) ?
In patients with low blood pressure ?
In patients in NYHA functional class IV ?
In patients receiving full dose of ACEi/A2RA stabilized for a while ?
In patients fullfilling the PARADIGM inclusion criteria but significant
functional MR complicated with pulmonary hyperension and severe
right ventricular dysfunction ?
In young patient fullfilling the PARADIGM inclusion ?
….

III and IV = 24%

McMurray. Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure, NEJM 2014

LIFE TRIAL: Entresto TM (LCZ696) In Advanced Heart
Failure (LIFE Study) (HFN-LIFE)




The primary objective of the study is to determine whether, in patients with symptomatic,
advanced heart failure due to left ventricular systolic dysfunction, treatment with LCZ696 for
24 weeks will improve Pro-B-type Natriuretic Peptide (NT-proBNP) levels, which reflect
hemodynamic and clinical status, compared to treatment with valsartan
Secondary Outcome Measures: Composite endpoint of the effects of LCZ696










alive and out of hospital
not listed for transplant (Status 1A or 1B)
not implanted with an LVAD (or scheduled for implant within 2 weeks)
not maintained or started on continuous inotropic therapy for ≥ 7 days
not hospitalized twice for HF (following the index admission)
Tolerability

400 participants




Estimated Primary Completion Date : September 30, 2019
Estimated Study Completion Date :
March 30, 2020

Rise your hand if you switch ACEi/A2RA to SV
1.
2.
3.
4.
5.

6.
7.

When eGFR is 33 ml/min/1.73 m² (Creatinin = 185 mol/l) ?
In patients with low blood pressure ?
In patients in NYHA functional class IV ?
In patients receiving full dose of ACEi/A2RA stabilized for a while ?
In patients fullfilling the PARADIGM inclusion criteria but having
significant functional MR complicated with pulmonary hyperension
and severe right ventricular dysfunction ?
In young patient fullfilling the PARADIGM inclusion criteria ?
….

Clinical case
45 yo male
Idiopathic cardiomyopathy
NYHA II
EF = 31%
ICD implanted 3 years ago
No decompensation over the past
4 years
BB 100% of RP
ACEi 100% of RP
MRA 100% of RP

Switch ACE  ARNI

PARADIGM: prespecified target dose of enalapril in
these trials was only 20 mg daily and not 40 mg daily

HEAAL, LOSARTAN

ATLAS, LISINOPRIL

Packer, Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group, CIR
Konstam, Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial, LANCET 2009

Neprilysin plays a critical role in maintaining the
homeostasis of amyloid-b peptide (Ab) in the brain

Vodovar, Neprilysin, cardiovascular, and Alzheimer’s diseases: the therapeutic split? , EHJ, 2015

Rise your hand if you switch ACEi/A2RA to SV
1.
2.
3.
4.
5.

6.
7.

When eGFR is 33 ml/min/1.73 m² (Creatinin = 185 mol/l) ?
In patients with low blood pressure ?
In patients in NYHA functional class IV ?
In patients receiving full dose of ACEi/A2RA stabilized for a while ?
In patients fullfilling the PARADIGM inclusion criteria but having
significant functional MR complicated with pulmonary hypertension
and severe right ventricular dysfunction ?
In young patient fullfilling the PARADIGM inclusion ?
….

Echocardiographic phenotype and prognostic
significance

Asgar, Secondary Mitral Regurgitation in Heart Failure: Pathophysiology, Prognosis, and Therapeutic Considerations JACC 2015
Pouleur, Prognostic value of right ventricular systolic dysfunction in heart failure with reduced ejection fraction, JACC 2018
Fukuta, Diastolic Versus Systolic Heart Failure, Diastolic Heart Failure (pp.119-133), 2008

A patient with « favorable » EF rEF

Conclusion
• ENTRESTO relatively safe in CK between 20 and 60 ml/min/m²
(neprilysin inhibition may have some renal protective effects)

• Risk of hyperkalemia was lower in PARADIGM-HF among patients
allocated to sacubitril/valsartan than those assigned to enalapril

• Hypotension limits ENTRESTO administration, but once prescribed
SV must be forced in an acceptable tolerance range

• SV administration should be investigated in various cardiac
phenotype (PH, RV dysfunction, MR, diastolic dysfunction, …)

• Care must be taken in apparently young, well stabilized patient
receiving full dose of ACEi, there is uncertainty on homeostasis of
amyloid-b peptide (PARAGON)


Documents similaires


Fichier PDF changer liec pour la sacubritil valsartanbauerfabrice2019
Fichier PDF periop heart failure cardiac surgery
Fichier PDF liver function heart failure
Fichier PDF choisir avec soin anglais
Fichier PDF domperidone reponse dr newman mars 2012
Fichier PDF perioperative management of chronic heart failure


Sur le même sujet..