SlideShare a Scribd company logo

Transition study and Pioneer HF study

Edgardo Kaplinsky
Edgardo Kaplinsky
Edgardo KaplinskyMedical Marketing Director en etal at etal

Sacubitril Valsartan overview Transition study preliminary results Pioneer HF study results

Transition study and Pioneer HF study

1 of 29
Download to read offline
Sacubitril/Valsartan
en IC FEVI reducida: novedades
TRANSITION
Randomized trial of pre-discharge vs. post-
discharge initiation of sacubitril/valsartan
PIONEER-HF
Comparison of sacubitril/valsartan versus
enalapril on effect on Ntpro-BNP in patients
stabilized from an acute heart failure episode
Fisiopatologíadela IC–FEVIreducida
Mecanismosneurohumorales
Francis et al. Ann Intern Med1984;101:370–7
Mecanismode progresióndela IC
Francis et al. Ann Intern Med1984;101:370–7
mecanismos
adaptativos
insuficientes
IC:estadode desequilibrioneuhumoral
mecanismos
maladaptativos
excesivosMcMurray. N Engl J Med 2010;362:228–38
Levin et al. N Engl J Med 1998;339;321–8; Gardner et al. Hypertension 2007;49:419–26;
Pandey. J Am Soc Hypertens 2008;2:210–6; Von Lueder et al. Pharmacol Ther 2014 [Epub ahead of print];
Potter. FEBS J 2011;278:1808–17; Lumsden et al. Curr Pharm Des 2010;16:4080–8; Mangiafico et al. Eur
Heart J 2013;34:886–93
Stimulated by the increase of cardiac wall stress: (volume and/or pressure overload)
Binding to receptor: causes conversion of GTP to cGMP (raises intracellular cGMP)
Metabolized by Neprilysin
 Origin: atrial cells
 Measurable (plasma)
 Origin: atrial /ventricular cells
 Measurable (plasma)
 Origin endothelial cells
 Non-measurable (plasma)
Local action -clearance of NP
Bone growth regulation
ANP – BNP
Respuesta endócrina alaIC:péptidos natriuréticos
Metabolism of NPs and other vasoactive peptides by
NEP1–9
1. Erdos, Skidgel. FASEB J 1989;3:145–51; 2. Levin et al. N Engl J Med 1998;339;321–8; 3. Stephenson et al. Biochem J 1987;243:183–7; 4. Lang et al. Clin Sci 1992;82:619–23; 5. Kenny
et al. Biochem J 1993;291:83–8; 6. Skidgel et al. Peptides 1984;5:769–76; 7. Abassi et al. Metabolism 1992;41:683–5; 8. Murphy et al. Br J Pharmacol 1994;113:137–42; 9. Jiang et al.
Hypertens Res 2004;27:109–17; 10. Langenickel & Dole. Drug Discovery Today: Ther Strateg 2012;9:e131–9; 11. Richards et al. J Hypertens 1993;11:407–16; 12. Ferro et al. Circulation
1998;97:2323–30
BNP / ANP
Ang I / Ang II Inactive
metabolites
NEP inhibition clinical
implications:
 NEP substrates may have
biological opposing actions10
 The total effect of the inhibition
depends on the net effect of the
individual metabolized
substrates 10
 The benefits of increasing the NPs
system may be lost by increasing
Ang II11
 A simultaneous suppression of
the RAAS is necessary 2,11,12
Adrenomedullin
Substance P
Bradykinin
Endothelin
Etc..
Neprilysin
 Zinc-dependent metalloproteinase / found on a large variety of tissues
 Particularly abundant in kidneys
Neprilisina: metaboliza multiples substratos con
diferente nivel deafinidad.

Recommended

Management strategy in HF with ARNI - Recent updates
Management strategy in HF with ARNI - Recent updates Management strategy in HF with ARNI - Recent updates
Management strategy in HF with ARNI - Recent updates Praveen Nagula
 
Summary of PROVE-HF and GUIDE-IT studies by Dr. Vaibhav Yawalkar MD, DM Cardi...
Summary of PROVE-HF and GUIDE-IT studies by Dr. Vaibhav Yawalkar MD, DM Cardi...Summary of PROVE-HF and GUIDE-IT studies by Dr. Vaibhav Yawalkar MD, DM Cardi...
Summary of PROVE-HF and GUIDE-IT studies by Dr. Vaibhav Yawalkar MD, DM Cardi...vaibhavyawalkar
 
Sacubitril Valsartan in Heart failure and Congenital heart disease
Sacubitril Valsartan in Heart failure and Congenital heart diseaseSacubitril Valsartan in Heart failure and Congenital heart disease
Sacubitril Valsartan in Heart failure and Congenital heart diseasepankaj bhosale
 
Pharmacotherapy in HFrEF
Pharmacotherapy in  HFrEFPharmacotherapy in  HFrEF
Pharmacotherapy in HFrEFdrucsamal
 

More Related Content

What's hot

New Treatments in HFrEF
New Treatments in HFrEFNew Treatments in HFrEF
New Treatments in HFrEFDuke Heart
 
Simultaneous or Rapid Sequence Initiation of Quadruple Therapy for HFrEF
Simultaneous or Rapid Sequence Initiation of Quadruple Therapy for HFrEFSimultaneous or Rapid Sequence Initiation of Quadruple Therapy for HFrEF
Simultaneous or Rapid Sequence Initiation of Quadruple Therapy for HFrEFDuke Heart
 
Angiotensin receptor-neprilysin inhibition(ARNI):The New Fronteir ?
Angiotensin receptor-neprilysin inhibition(ARNI):The New Fronteir ?Angiotensin receptor-neprilysin inhibition(ARNI):The New Fronteir ?
Angiotensin receptor-neprilysin inhibition(ARNI):The New Fronteir ?drucsamal
 
ARNI as new standard of care in Heart Failure
ARNI as  new  standard of care in Heart Failure ARNI as  new  standard of care in Heart Failure
ARNI as new standard of care in Heart Failure SYEDRAZA56411
 
DELIVER delivered 2022.pptx
DELIVER delivered 2022.pptxDELIVER delivered 2022.pptx
DELIVER delivered 2022.pptxhospital
 
SHIFT trial - Summary & Results
SHIFT trial - Summary & ResultsSHIFT trial - Summary & Results
SHIFT trial - Summary & Resultstheheart.org
 
Paradigm hf journal club presentation
Paradigm hf journal club presentationParadigm hf journal club presentation
Paradigm hf journal club presentationGOPAL GHOSH
 
Role of statin and clopidogrel in atherothrombotic events
Role of statin and clopidogrel in atherothrombotic eventsRole of statin and clopidogrel in atherothrombotic events
Role of statin and clopidogrel in atherothrombotic eventsPraveen Nagula
 
Evidence-based management of CHF
Evidence-based management of CHFEvidence-based management of CHF
Evidence-based management of CHFMedPeds Hospitalist
 
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment options
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment optionsSGLT2 inhibitors in Heart failure: A prized addition to HF treatment options
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment optionsahvc0858
 
Ticagrelor in acute myocardial infarction
Ticagrelor in acute myocardial infarctionTicagrelor in acute myocardial infarction
Ticagrelor in acute myocardial infarctionVasif Mayan
 
Newer trends in heart failure by Dr. Vaibhav Yawalkar MD DM Cardiology, Consu...
Newer trends in heart failure by Dr. Vaibhav Yawalkar MD DM Cardiology, Consu...Newer trends in heart failure by Dr. Vaibhav Yawalkar MD DM Cardiology, Consu...
Newer trends in heart failure by Dr. Vaibhav Yawalkar MD DM Cardiology, Consu...vaibhavyawalkar
 

What's hot (20)

New Treatments in HFrEF
New Treatments in HFrEFNew Treatments in HFrEF
New Treatments in HFrEF
 
PROVE HF Study
PROVE HF StudyPROVE HF Study
PROVE HF Study
 
Heart failure management - role of arni
Heart failure management - role of arniHeart failure management - role of arni
Heart failure management - role of arni
 
New Frontiers in Managing Heart Failure: Are SGLT2 Inhibitors the Next Leap F...
New Frontiers in Managing Heart Failure: Are SGLT2 Inhibitors the Next Leap F...New Frontiers in Managing Heart Failure: Are SGLT2 Inhibitors the Next Leap F...
New Frontiers in Managing Heart Failure: Are SGLT2 Inhibitors the Next Leap F...
 
Simultaneous or Rapid Sequence Initiation of Quadruple Therapy for HFrEF
Simultaneous or Rapid Sequence Initiation of Quadruple Therapy for HFrEFSimultaneous or Rapid Sequence Initiation of Quadruple Therapy for HFrEF
Simultaneous or Rapid Sequence Initiation of Quadruple Therapy for HFrEF
 
Angiotensin receptor-neprilysin inhibition(ARNI):The New Fronteir ?
Angiotensin receptor-neprilysin inhibition(ARNI):The New Fronteir ?Angiotensin receptor-neprilysin inhibition(ARNI):The New Fronteir ?
Angiotensin receptor-neprilysin inhibition(ARNI):The New Fronteir ?
 
ARNI as new standard of care in Heart Failure
ARNI as  new  standard of care in Heart Failure ARNI as  new  standard of care in Heart Failure
ARNI as new standard of care in Heart Failure
 
PIONEER HF Study
PIONEER HF StudyPIONEER HF Study
PIONEER HF Study
 
DELIVER delivered 2022.pptx
DELIVER delivered 2022.pptxDELIVER delivered 2022.pptx
DELIVER delivered 2022.pptx
 
SHIFT trial - Summary & Results
SHIFT trial - Summary & ResultsSHIFT trial - Summary & Results
SHIFT trial - Summary & Results
 
Paradigm hf journal club presentation
Paradigm hf journal club presentationParadigm hf journal club presentation
Paradigm hf journal club presentation
 
Sacubitril valsartan EK
Sacubitril valsartan EKSacubitril valsartan EK
Sacubitril valsartan EK
 
Role of statin and clopidogrel in atherothrombotic events
Role of statin and clopidogrel in atherothrombotic eventsRole of statin and clopidogrel in atherothrombotic events
Role of statin and clopidogrel in atherothrombotic events
 
Evidence-based management of CHF
Evidence-based management of CHFEvidence-based management of CHF
Evidence-based management of CHF
 
Rivaroxaban
RivaroxabanRivaroxaban
Rivaroxaban
 
Role of SGLT2i in cardio-renal protection
Role of SGLT2i in cardio-renal protectionRole of SGLT2i in cardio-renal protection
Role of SGLT2i in cardio-renal protection
 
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment options
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment optionsSGLT2 inhibitors in Heart failure: A prized addition to HF treatment options
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment options
 
Trials of ace inhibitors
Trials of ace inhibitorsTrials of ace inhibitors
Trials of ace inhibitors
 
Ticagrelor in acute myocardial infarction
Ticagrelor in acute myocardial infarctionTicagrelor in acute myocardial infarction
Ticagrelor in acute myocardial infarction
 
Newer trends in heart failure by Dr. Vaibhav Yawalkar MD DM Cardiology, Consu...
Newer trends in heart failure by Dr. Vaibhav Yawalkar MD DM Cardiology, Consu...Newer trends in heart failure by Dr. Vaibhav Yawalkar MD DM Cardiology, Consu...
Newer trends in heart failure by Dr. Vaibhav Yawalkar MD DM Cardiology, Consu...
 

Similar to Transition study and Pioneer HF study

early initiation of arni.pptx
early initiation of arni.pptxearly initiation of arni.pptx
early initiation of arni.pptxdkapila2002
 
Serelaxin in acute heart failure
Serelaxin in acute heart failureSerelaxin in acute heart failure
Serelaxin in acute heart failuredrucsamal
 
02 Sperati Prevention And Management Of Acute Renal Failure
02 Sperati   Prevention And Management Of Acute Renal Failure02 Sperati   Prevention And Management Of Acute Renal Failure
02 Sperati Prevention And Management Of Acute Renal FailureDang Thanh Tuan
 
02 Sperati Prevention And Management Of Acute Renal Failure
02 Sperati   Prevention And Management Of Acute Renal Failure02 Sperati   Prevention And Management Of Acute Renal Failure
02 Sperati Prevention And Management Of Acute Renal Failureguest2379201
 
Hypertension management- Angina IHD
Hypertension management- Angina IHDHypertension management- Angina IHD
Hypertension management- Angina IHDcardiositeindia
 
PIONEER-HF Journal
PIONEER-HF JournalPIONEER-HF Journal
PIONEER-HF JournalBeka Aberra
 
How Early ARNI is Early.pptx
How Early ARNI is Early.pptxHow Early ARNI is Early.pptx
How Early ARNI is Early.pptxPuneetGupta542512
 
Valsartan,Aml ,Changing the Landscape of BP Management.pptx
Valsartan,Aml ,Changing the Landscape of BP Management.pptxValsartan,Aml ,Changing the Landscape of BP Management.pptx
Valsartan,Aml ,Changing the Landscape of BP Management.pptxRITASALEH9
 
Pepe R. Nuovi Anticoagulanti. ASMaD 2013
Pepe R. Nuovi Anticoagulanti. ASMaD 2013Pepe R. Nuovi Anticoagulanti. ASMaD 2013
Pepe R. Nuovi Anticoagulanti. ASMaD 2013Gianfranco Tammaro
 
anticoagulation eng.pptx
anticoagulation eng.pptxanticoagulation eng.pptx
anticoagulation eng.pptxAdliIsmail4
 
Dabigatran vs warfain Prior to TEE Journal Club
Dabigatran vs warfain Prior to TEE Journal ClubDabigatran vs warfain Prior to TEE Journal Club
Dabigatran vs warfain Prior to TEE Journal ClubMichael Katz
 
Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...
Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...
Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...cacao83
 
How Early ARNI is Early.pptx
How Early ARNI is Early.pptxHow Early ARNI is Early.pptx
How Early ARNI is Early.pptxPuneetGupta542512
 

Similar to Transition study and Pioneer HF study (20)

NOAC.pdf
NOAC.pdfNOAC.pdf
NOAC.pdf
 
early initiation of arni.pptx
early initiation of arni.pptxearly initiation of arni.pptx
early initiation of arni.pptx
 
Serelaxin in acute heart failure
Serelaxin in acute heart failureSerelaxin in acute heart failure
Serelaxin in acute heart failure
 
Top 3 Hits en Insuficiencia cardiaca en 2014
Top 3 Hits en Insuficiencia cardiaca en 2014Top 3 Hits en Insuficiencia cardiaca en 2014
Top 3 Hits en Insuficiencia cardiaca en 2014
 
02 Sperati Prevention And Management Of Acute Renal Failure
02 Sperati   Prevention And Management Of Acute Renal Failure02 Sperati   Prevention And Management Of Acute Renal Failure
02 Sperati Prevention And Management Of Acute Renal Failure
 
02 Sperati Prevention And Management Of Acute Renal Failure
02 Sperati   Prevention And Management Of Acute Renal Failure02 Sperati   Prevention And Management Of Acute Renal Failure
02 Sperati Prevention And Management Of Acute Renal Failure
 
Novedades en el manejo de la Insuficiencia Cardiaca Crónica
Novedades en el manejo de la Insuficiencia Cardiaca CrónicaNovedades en el manejo de la Insuficiencia Cardiaca Crónica
Novedades en el manejo de la Insuficiencia Cardiaca Crónica
 
Hypertension management- Angina IHD
Hypertension management- Angina IHDHypertension management- Angina IHD
Hypertension management- Angina IHD
 
PIONEER-HF Journal
PIONEER-HF JournalPIONEER-HF Journal
PIONEER-HF Journal
 
How Early ARNI is Early.pptx
How Early ARNI is Early.pptxHow Early ARNI is Early.pptx
How Early ARNI is Early.pptx
 
Valsartan,Aml ,Changing the Landscape of BP Management.pptx
Valsartan,Aml ,Changing the Landscape of BP Management.pptxValsartan,Aml ,Changing the Landscape of BP Management.pptx
Valsartan,Aml ,Changing the Landscape of BP Management.pptx
 
Pepe R. Nuovi Anticoagulanti. ASMaD 2013
Pepe R. Nuovi Anticoagulanti. ASMaD 2013Pepe R. Nuovi Anticoagulanti. ASMaD 2013
Pepe R. Nuovi Anticoagulanti. ASMaD 2013
 
Serelaxin.
Serelaxin.Serelaxin.
Serelaxin.
 
Serelaxin.
Serelaxin.Serelaxin.
Serelaxin.
 
ACC 2020 UPDATES
ACC 2020 UPDATESACC 2020 UPDATES
ACC 2020 UPDATES
 
anticoagulation eng.pptx
anticoagulation eng.pptxanticoagulation eng.pptx
anticoagulation eng.pptx
 
Dabigatran vs warfain Prior to TEE Journal Club
Dabigatran vs warfain Prior to TEE Journal ClubDabigatran vs warfain Prior to TEE Journal Club
Dabigatran vs warfain Prior to TEE Journal Club
 
Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...
Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...
Thuốc điều trị tăng huyết áp trên bệnh thận đái tháo đường - BS Phạm Văn Bù...
 
How Early ARNI is Early.pptx
How Early ARNI is Early.pptxHow Early ARNI is Early.pptx
How Early ARNI is Early.pptx
 
BEST OF ESC 2020
BEST OF ESC 2020BEST OF ESC 2020
BEST OF ESC 2020
 

More from Edgardo Kaplinsky

Paradigm hf-trial-ppt-pptx - copia
Paradigm hf-trial-ppt-pptx - copiaParadigm hf-trial-ppt-pptx - copia
Paradigm hf-trial-ppt-pptx - copiaEdgardo Kaplinsky
 
Semex, Sociedad Española de Médicos Extranjeros
Semex, Sociedad Española de Médicos ExtranjerosSemex, Sociedad Española de Médicos Extranjeros
Semex, Sociedad Española de Médicos ExtranjerosEdgardo Kaplinsky
 
Ivabradina, utilidad clínica de la reducción de la frecuencia cardiaca
Ivabradina, utilidad clínica de la reducción de la frecuencia cardiacaIvabradina, utilidad clínica de la reducción de la frecuencia cardiaca
Ivabradina, utilidad clínica de la reducción de la frecuencia cardiacaEdgardo Kaplinsky
 
Miocardiopatia no compactada
Miocardiopatia no compactadaMiocardiopatia no compactada
Miocardiopatia no compactadaEdgardo Kaplinsky
 
Insuficiencia cardiaca. revision de tratamiento a partir de un caso clinico
Insuficiencia cardiaca. revision de tratamiento a partir de un caso clinicoInsuficiencia cardiaca. revision de tratamiento a partir de un caso clinico
Insuficiencia cardiaca. revision de tratamiento a partir de un caso clinicoEdgardo Kaplinsky
 

More from Edgardo Kaplinsky (9)

Polypill
PolypillPolypill
Polypill
 
Dabigatrán + idarucizumab
Dabigatrán + idarucizumab Dabigatrán + idarucizumab
Dabigatrán + idarucizumab
 
Paradigm hf-trial-ppt-pptx - copia
Paradigm hf-trial-ppt-pptx - copiaParadigm hf-trial-ppt-pptx - copia
Paradigm hf-trial-ppt-pptx - copia
 
Semex, Sociedad Española de Médicos Extranjeros
Semex, Sociedad Española de Médicos ExtranjerosSemex, Sociedad Española de Médicos Extranjeros
Semex, Sociedad Española de Médicos Extranjeros
 
Ivabradina, utilidad clínica de la reducción de la frecuencia cardiaca
Ivabradina, utilidad clínica de la reducción de la frecuencia cardiacaIvabradina, utilidad clínica de la reducción de la frecuencia cardiaca
Ivabradina, utilidad clínica de la reducción de la frecuencia cardiaca
 
Tratamiento antianginoso
Tratamiento antianginosoTratamiento antianginoso
Tratamiento antianginoso
 
Miocardiopatia no compactada
Miocardiopatia no compactadaMiocardiopatia no compactada
Miocardiopatia no compactada
 
Insuficiencia cardiaca. revision de tratamiento a partir de un caso clinico
Insuficiencia cardiaca. revision de tratamiento a partir de un caso clinicoInsuficiencia cardiaca. revision de tratamiento a partir de un caso clinico
Insuficiencia cardiaca. revision de tratamiento a partir de un caso clinico
 
Transplante cardiaco
Transplante cardiacoTransplante cardiaco
Transplante cardiaco
 

Recently uploaded

Seminario BioMol- Aura Cristina Peña Santos
Seminario BioMol- Aura Cristina Peña SantosSeminario BioMol- Aura Cristina Peña Santos
Seminario BioMol- Aura Cristina Peña SantosAuraCristinaPeaSanto
 
Cell cytoskeleton and molecular motors.pdf
Cell cytoskeleton and molecular motors.pdfCell cytoskeleton and molecular motors.pdf
Cell cytoskeleton and molecular motors.pdfMedicoseAcademics
 
odontogenic keratocyst a developmental cyst
odontogenic keratocyst  a developmental cystodontogenic keratocyst  a developmental cyst
odontogenic keratocyst a developmental cystJani253068
 
Feel and Look Years Younger With Nutra IGF 1 Supplement
Feel and Look Years Younger With Nutra IGF 1 SupplementFeel and Look Years Younger With Nutra IGF 1 Supplement
Feel and Look Years Younger With Nutra IGF 1 SupplementWintersBiotechnology
 
Target pain receptors with essential oils
Target pain receptors with essential oilsTarget pain receptors with essential oils
Target pain receptors with essential oilsKevin KF Ng
 
FEBRUARY 2024 ONCOLOGY CARTOON /95TH VOLUME
FEBRUARY 2024 ONCOLOGY CARTOON /95TH VOLUMEFEBRUARY 2024 ONCOLOGY CARTOON /95TH VOLUME
FEBRUARY 2024 ONCOLOGY CARTOON /95TH VOLUMEKanhu Charan
 
https://getneurozoom.cc/welcome#aff=musvi5
https://getneurozoom.cc/welcome#aff=musvi5https://getneurozoom.cc/welcome#aff=musvi5
https://getneurozoom.cc/welcome#aff=musvi5Hussain Syed
 
TRANSPORT PROCESS ACROSS CELL MEMBRANE.pptx
TRANSPORT PROCESS ACROSS CELL MEMBRANE.pptxTRANSPORT PROCESS ACROSS CELL MEMBRANE.pptx
TRANSPORT PROCESS ACROSS CELL MEMBRANE.pptxPoojaDahale3
 
pediatrics. epilepsy and seizures in children 8.ppt
pediatrics. epilepsy and seizures in children 8.pptpediatrics. epilepsy and seizures in children 8.ppt
pediatrics. epilepsy and seizures in children 8.pptArun170190
 
SCIENTIFIC APPROACH OF DIET IN MASANUMASIKA GARBINI PARICHARYA – FOR A HEALTH...
SCIENTIFIC APPROACH OF DIET IN MASANUMASIKA GARBINI PARICHARYA – FOR A HEALTH...SCIENTIFIC APPROACH OF DIET IN MASANUMASIKA GARBINI PARICHARYA – FOR A HEALTH...
SCIENTIFIC APPROACH OF DIET IN MASANUMASIKA GARBINI PARICHARYA – FOR A HEALTH...Dr. Madduru Muni Haritha
 
Carpal, Meta Carpal, Tarsal Meta Tarsal & Phalanges By M Thiru murugan.pptx
Carpal, Meta Carpal, Tarsal Meta Tarsal & Phalanges By M Thiru murugan.pptxCarpal, Meta Carpal, Tarsal Meta Tarsal & Phalanges By M Thiru murugan.pptx
Carpal, Meta Carpal, Tarsal Meta Tarsal & Phalanges By M Thiru murugan.pptxthiru murugan
 
Anatomy and Physiology of Optic Nerve Dr.PrabhatDevkota.pptx
Anatomy and Physiology of Optic Nerve Dr.PrabhatDevkota.pptxAnatomy and Physiology of Optic Nerve Dr.PrabhatDevkota.pptx
Anatomy and Physiology of Optic Nerve Dr.PrabhatDevkota.pptxDr. Prabhat Devkota, MD
 
Seminario Biología Molecular, Luisa Maradey
Seminario Biología Molecular, Luisa MaradeySeminario Biología Molecular, Luisa Maradey
Seminario Biología Molecular, Luisa Maradeylmaradeya
 
Tolerance Hydra10P Avene trainings blink
Tolerance Hydra10P Avene trainings blinkTolerance Hydra10P Avene trainings blink
Tolerance Hydra10P Avene trainings blinkClinicians
 
Renal Regulation of Potassium, Calcium, Magnesium and Phosphorus
Renal Regulation of Potassium, Calcium, Magnesium and PhosphorusRenal Regulation of Potassium, Calcium, Magnesium and Phosphorus
Renal Regulation of Potassium, Calcium, Magnesium and PhosphorusMedicoseAcademics
 
The Natural Method That Supports Healthy Weight Loss & Steady Blood Sugar Levels
The Natural Method That Supports Healthy Weight Loss & Steady Blood Sugar LevelsThe Natural Method That Supports Healthy Weight Loss & Steady Blood Sugar Levels
The Natural Method That Supports Healthy Weight Loss & Steady Blood Sugar LevelsAman Ullah
 

Recently uploaded (20)

Introduction Endocrine -1.pptx
Introduction Endocrine -1.pptxIntroduction Endocrine -1.pptx
Introduction Endocrine -1.pptx
 
Seminario BioMol- Aura Cristina Peña Santos
Seminario BioMol- Aura Cristina Peña SantosSeminario BioMol- Aura Cristina Peña Santos
Seminario BioMol- Aura Cristina Peña Santos
 
Cell cytoskeleton and molecular motors.pdf
Cell cytoskeleton and molecular motors.pdfCell cytoskeleton and molecular motors.pdf
Cell cytoskeleton and molecular motors.pdf
 
odontogenic keratocyst a developmental cyst
odontogenic keratocyst  a developmental cystodontogenic keratocyst  a developmental cyst
odontogenic keratocyst a developmental cyst
 
Feel and Look Years Younger With Nutra IGF 1 Supplement
Feel and Look Years Younger With Nutra IGF 1 SupplementFeel and Look Years Younger With Nutra IGF 1 Supplement
Feel and Look Years Younger With Nutra IGF 1 Supplement
 
Target pain receptors with essential oils
Target pain receptors with essential oilsTarget pain receptors with essential oils
Target pain receptors with essential oils
 
Respirtory stimulants.pdf
Respirtory stimulants.pdfRespirtory stimulants.pdf
Respirtory stimulants.pdf
 
FEBRUARY 2024 ONCOLOGY CARTOON /95TH VOLUME
FEBRUARY 2024 ONCOLOGY CARTOON /95TH VOLUMEFEBRUARY 2024 ONCOLOGY CARTOON /95TH VOLUME
FEBRUARY 2024 ONCOLOGY CARTOON /95TH VOLUME
 
https://getneurozoom.cc/welcome#aff=musvi5
https://getneurozoom.cc/welcome#aff=musvi5https://getneurozoom.cc/welcome#aff=musvi5
https://getneurozoom.cc/welcome#aff=musvi5
 
Expectorants and Antitussives.pdf
Expectorants and Antitussives.pdfExpectorants and Antitussives.pdf
Expectorants and Antitussives.pdf
 
TRANSPORT PROCESS ACROSS CELL MEMBRANE.pptx
TRANSPORT PROCESS ACROSS CELL MEMBRANE.pptxTRANSPORT PROCESS ACROSS CELL MEMBRANE.pptx
TRANSPORT PROCESS ACROSS CELL MEMBRANE.pptx
 
pediatrics. epilepsy and seizures in children 8.ppt
pediatrics. epilepsy and seizures in children 8.pptpediatrics. epilepsy and seizures in children 8.ppt
pediatrics. epilepsy and seizures in children 8.ppt
 
Nasal Decongestants.pdf
Nasal Decongestants.pdfNasal Decongestants.pdf
Nasal Decongestants.pdf
 
SCIENTIFIC APPROACH OF DIET IN MASANUMASIKA GARBINI PARICHARYA – FOR A HEALTH...
SCIENTIFIC APPROACH OF DIET IN MASANUMASIKA GARBINI PARICHARYA – FOR A HEALTH...SCIENTIFIC APPROACH OF DIET IN MASANUMASIKA GARBINI PARICHARYA – FOR A HEALTH...
SCIENTIFIC APPROACH OF DIET IN MASANUMASIKA GARBINI PARICHARYA – FOR A HEALTH...
 
Carpal, Meta Carpal, Tarsal Meta Tarsal & Phalanges By M Thiru murugan.pptx
Carpal, Meta Carpal, Tarsal Meta Tarsal & Phalanges By M Thiru murugan.pptxCarpal, Meta Carpal, Tarsal Meta Tarsal & Phalanges By M Thiru murugan.pptx
Carpal, Meta Carpal, Tarsal Meta Tarsal & Phalanges By M Thiru murugan.pptx
 
Anatomy and Physiology of Optic Nerve Dr.PrabhatDevkota.pptx
Anatomy and Physiology of Optic Nerve Dr.PrabhatDevkota.pptxAnatomy and Physiology of Optic Nerve Dr.PrabhatDevkota.pptx
Anatomy and Physiology of Optic Nerve Dr.PrabhatDevkota.pptx
 
Seminario Biología Molecular, Luisa Maradey
Seminario Biología Molecular, Luisa MaradeySeminario Biología Molecular, Luisa Maradey
Seminario Biología Molecular, Luisa Maradey
 
Tolerance Hydra10P Avene trainings blink
Tolerance Hydra10P Avene trainings blinkTolerance Hydra10P Avene trainings blink
Tolerance Hydra10P Avene trainings blink
 
Renal Regulation of Potassium, Calcium, Magnesium and Phosphorus
Renal Regulation of Potassium, Calcium, Magnesium and PhosphorusRenal Regulation of Potassium, Calcium, Magnesium and Phosphorus
Renal Regulation of Potassium, Calcium, Magnesium and Phosphorus
 
The Natural Method That Supports Healthy Weight Loss & Steady Blood Sugar Levels
The Natural Method That Supports Healthy Weight Loss & Steady Blood Sugar LevelsThe Natural Method That Supports Healthy Weight Loss & Steady Blood Sugar Levels
The Natural Method That Supports Healthy Weight Loss & Steady Blood Sugar Levels
 

Transition study and Pioneer HF study

  • 1. Sacubitril/Valsartan en IC FEVI reducida: novedades TRANSITION Randomized trial of pre-discharge vs. post- discharge initiation of sacubitril/valsartan PIONEER-HF Comparison of sacubitril/valsartan versus enalapril on effect on Ntpro-BNP in patients stabilized from an acute heart failure episode
  • 3. Mecanismode progresióndela IC Francis et al. Ann Intern Med1984;101:370–7
  • 5. Levin et al. N Engl J Med 1998;339;321–8; Gardner et al. Hypertension 2007;49:419–26; Pandey. J Am Soc Hypertens 2008;2:210–6; Von Lueder et al. Pharmacol Ther 2014 [Epub ahead of print]; Potter. FEBS J 2011;278:1808–17; Lumsden et al. Curr Pharm Des 2010;16:4080–8; Mangiafico et al. Eur Heart J 2013;34:886–93 Stimulated by the increase of cardiac wall stress: (volume and/or pressure overload) Binding to receptor: causes conversion of GTP to cGMP (raises intracellular cGMP) Metabolized by Neprilysin  Origin: atrial cells  Measurable (plasma)  Origin: atrial /ventricular cells  Measurable (plasma)  Origin endothelial cells  Non-measurable (plasma) Local action -clearance of NP Bone growth regulation ANP – BNP Respuesta endócrina alaIC:péptidos natriuréticos
  • 6. Metabolism of NPs and other vasoactive peptides by NEP1–9 1. Erdos, Skidgel. FASEB J 1989;3:145–51; 2. Levin et al. N Engl J Med 1998;339;321–8; 3. Stephenson et al. Biochem J 1987;243:183–7; 4. Lang et al. Clin Sci 1992;82:619–23; 5. Kenny et al. Biochem J 1993;291:83–8; 6. Skidgel et al. Peptides 1984;5:769–76; 7. Abassi et al. Metabolism 1992;41:683–5; 8. Murphy et al. Br J Pharmacol 1994;113:137–42; 9. Jiang et al. Hypertens Res 2004;27:109–17; 10. Langenickel & Dole. Drug Discovery Today: Ther Strateg 2012;9:e131–9; 11. Richards et al. J Hypertens 1993;11:407–16; 12. Ferro et al. Circulation 1998;97:2323–30 BNP / ANP Ang I / Ang II Inactive metabolites NEP inhibition clinical implications:  NEP substrates may have biological opposing actions10  The total effect of the inhibition depends on the net effect of the individual metabolized substrates 10  The benefits of increasing the NPs system may be lost by increasing Ang II11  A simultaneous suppression of the RAAS is necessary 2,11,12 Adrenomedullin Substance P Bradykinin Endothelin Etc.. Neprilysin  Zinc-dependent metalloproteinase / found on a large variety of tissues  Particularly abundant in kidneys Neprilisina: metaboliza multiples substratos con diferente nivel deafinidad.
  • 7. 7 Sacubitril/Valsartan: inhibición simultánea de NEP (LBQ657) ydel receptor AT1(valsartan) 1. Bloch, Basile. J Clin Hypertens 2010;12:809–12; 2. Gu et al. J Clin Pharmacol 2010;50:401–14; 3. Langenickel & Dole. Drug Discov Today: Ther Strateg 2012;9:e131–9 Vasodilatation  Blood pressure  Sympathetic tone  Aldosterone levels  Fibrosis  Hypertrophy  Natriuresis/diuresis Inactive fragments ANP, BNP, CNP, others vasoactive peptides* AT1 receptor Vasoconstriction  Blood pressure  Sympathetic tone  Aldosterone  Fibrosis  Hypertrophy Angiotensinogen (liver secretion ) Ang I Ang II RAAS LCZ696 SACUBITRIL (AHU377; prodrug) Inhibiting Stimulating LBQ657 (iNEP inhibitor) OH O HN O HO O VALSARTAN N NHN N N O OH O *Sustratos de neprilisina listados en orden de relativa afinidad por NEP: ANP, CNP, Ang II, Ang I, adrenomedullna, sustancia P, bradiquinina, endotelina-1, BNP Levin et al. N Engl J Med 1998;339:321–8; Nathisuwan & Talbert. Pharmacotherapy 2002;22:27–42; Schrier & Abraham N Engl J Med 1999;341:577–85; Langenickel & Dole. Drug Discov Today: Ther Strateg 2012;9:e131–9; Feng et al. Tetrahedron Letters 2012;53:275–6
  • 9. 9 Inclusion: • ≥ 18 y.o / NYHA class II-IV / HF. LVEF ≤40 % (≤35% amend) •BNP ≥150 /NT-proBNP ≥600 (pg/mL) or BNP ≥100 / NT-proBNP ≥400 (pg/mL) hosp within 12 mo. •Guideline use of BB & MRA antagonists / ACEi or ARB equivalent to enalapril 10 mg (4 weeks) •SBP ≥ 100 mm Hg (run-in) / ≥ 95 mmHg (randomization) •eGFR ≥ 30 ml/min/1.73 m2 / no decrease >25%. (amend to 35%) and K < 5.2 mmol/l PARADIGM-HF: Prospective comparisonofARNIwithACEito Determine ImpactonGlobal Mortality andmorbidityin HF 36 hs washing period 36 hs washing period
  • 10. 10 PARADIGM-HF: resultados endpoints primarios ysecundarios McMurray, et al. N Engl J Med 2014;371(11):993-1004;
  • 11. 11 40 mg 80 mg 160 mg (valsartan) Peak concentrations LBQ657 & valsartan: reached at the same time (1,5-4,5 hs) Steady state levels sacubitril, LBQ657 and valsartan: achieved in 3 days Sacubitril is mainly eliminated in urine (52-68%); valsartan mainly via feces (86%). LCZ696 :sacubitril /valsartan 1er ARNI:angiotensin receptor -neprilysin inhibitor X 2 STUDY MEDICATION: 50 mg delivers the equivalent of 40 mg of valsartan 100 mg delivers the equivalent of 80 mg of valsartan 200 mg delivers the equivalent of 160 mg of valsartan
  • 12. Inicio de Sacubitril/Valsartan en pacientes hospitalizados con IC-FEVI reducida tras estabilización hemodinámica Wachter R, et al. Abstract P6531. European Society of Cardiology Congress; Aug. 25-29, 2018; Munich. TRANSITION Randomized trial of pre-discharge vs. post- discharge initiation of sacubitril/valsartan
  • 13. 13 TRANSITION: randomized trialofpre-discharge vs. post-discharge initiation ofsacubitril/valsartan Heart Failure 2018; 5: 327–336
  • 14. 14 TRANSITION: randomized trialofpre-discharge vs. post-discharge initiation ofsacubitril/valsartan Heart Failure 2018; 5: 327–336
  • 15. 17Wachter R, et al. Abstract P6531. European Society of Cardiology Congress; Aug. 25-29, 2018; Munich. TRANSITION study: Inclusión &Demografia “de novo” HF: 29% Naive 24% Entry criteria ≥18 years hospitalized for an episode of ADHF (de novo HF or worsening chronic HF) NYHA II–IV and LVEF≤ 40%. ACEI, ARB or Naive
  • 16. 18 TRANSITION: resultados similares preypost-alta Wachter R, et al. Abstract P6531. European Society of Cardiology Congress; Aug. 25-29, 2018; Munich.
  • 17. 19 TRANSITION: randomized trialofpre-discharge vs. post-discharge initiation ofsacubitril/valsartan PRE-DISCHARGE POST-DISCHARGE Serious adverse events : 18,9% 17,7% Cardiac failure: 7,0% 7,7% Acute renal injury: 1,2% 1,4% Hypotension: 0,8% 0,4% Hyperkalemia: 0,6% 0,4% Mortality: 2,6% 2,0% Wachter R, et al. Abstract P6531. European Society of Cardiology Congress; Aug. 25-29, 2018; Munich. PREDICTORS FOR SUCCESSFUL SAC/VAL DOSE UP-TITRATION (200 mg BID) Age : <65 vs. >65 y.o eGFR: > 60 vs. <60 ml.min.1,73m2 SBP >120 vs 100 to 120 mm Hg Prior HF: y/n Hypertension: y/n AF: y/n Start dose 100 vs 50 mg BID Treatment: post vs pre discharge
  • 18. 20 TRANSITION: conclusiones Wachter R, et al. Abstract P6531. European Society of Cardiology Congress; Aug. 25-29, 2018; Munich. About 50% of the HFrEF patients stabilized after an ADHF event achieved the recommended dose of 200 mg Sac/Val BID within 10 weeks Sac/Val can be initiated early and safely in patients shortly after an ADHF episode The number of patients who met the primary and secondary endpoints was similar across both treatment arms. The incidence of adverse events and discontinuations of Sac/Val due to adverse events was also similar in both the in-hospital and the out-patient setting
  • 19. ComParIson Of Sacubitril/valsartaN Versus Enalapril on Effect on ntpRo-bnp in Patients Stabilized From an Acute Heart Failure Episode. (PIONEER-HF)
  • 20. Primary Outcome (EFFICACY) Percentage change from baseline in N-terminal pro-brain natriuretic peptide (NT- proBNP) [ Baseline, Week 4 and Week 8 ] Secondary Outcome (SAFETY) Number of patients with incidences of Symptomatic hypotension [ 8 weeks ] Number of patients with incidences of hyperkalemia [ 8 weeks ] (Potassium>5.5 meq/l) Number of incidences of Angioedema [ 8 weeks ] Change from baseline in high sensitivity troponin [Baseline, Week 4 and Week 8 ] Change from baseline in urinary cGMP [ Baseline, Week 4 and Week 8 ] Change from baseline in BNP to NTproBNP ratio [ Baseline, Week 4 and Week 8 ]
  • 21. Key Inclusion Criteria: 1. Currently hospitalized for ADHF. / 18 y.o or older 2. Symptoms and signs of fluid overload presence (i.e. jugular venous distention, edema or rales on auscultation or pulmonary congestion on chest x-ray). 3. Randomization no earlier than 24 hours and up to ten days after presentation while still hospitalized as long as meet the following definition of stable status: •SBP ≥100mm Hg for the preceding 6 hours prior to randomization; •No increase in i.v. diuretic dose within last 6 hs prior to randomization •No i.v. inotropic drugs for 24 hours prior to randomization •No i.v. vasodilators including nitrates within last 6 hours prior to randomization 4. LVEF ≤40% within the past 6 months 5. Elevated NT-proBNP ≥ 1600pg/mL or BNP ≥400 pg/mL during hospitalization Key Exclusion Criteria: 1. eGFR < 30 ml/min/1.73 m2. 2. Serum potassium > 5.2 mEq/L at screening
  • 22. Dose level Sacubitril/valsartan Enalapril 1 24/26 mg BID 2.5 mg BID 2 49/51 mg BID 5 mg BID 3 97/103 mg BID 10 mg BID
  • 25. • 68 hs: median time of enrrollment (48-98 hs) • At randomization: peripheral edemas: 61,7% / rales: 32,9% • Before randomization: 93% (IV furosemide), 97% (care unit) 7,7% IV inotropes)
  • 28. Conclusions Among patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure, the initiation of sacubitril–valsartan therapy led to a greater reduction in the NT-proBNP concentration than enalapril therapy. Rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups
  • 29. 46,7% vs 25,3% NT.proBNP ratio of change Sac/Val vs Enalapril 50% of patients stabilized after an ADHF event achieved the top dose of Sac/Val BID within 10 weeks 20% reduction of the risk of death from CV 21 % reduction of HF hospitalizations 16% reduction of the risk of all-cause mortality Sac/Val vs Enalapril SACUBITRIL/VALSARTAN en IC

Editor's Notes

  1. Apartir de aki es cuando se empiesza a explicar. Hasta ahora todo a sido centrado en la parte de la dereccha
  2. Los PN descubiertos en los años 30, son liberados por el corazon y en sangre actuan como hormonas. ANP( sintetizado en auricula), CNP( endotelio) y BNP (pared ventricular) En el contexto de la expansión de volumen o la sobrecarga de presión, el estrés de la pared resultante inicia la síntesis de pre-proBNP en el miocardio ventricula El BNP es el de vida media mas larga por eso se usa como marcador, aunque A yC tb tienen efectos potentes. El BNP se sintetiza ppalmente en el ventriculo. Corina y furina degrada proBNP en NT-proBNP y BNP