1) The document discusses heart failure, including definitions, classifications, epidemiology, and treatment. It summarizes key findings from the PARADIGM-HF trial which compared the drug Entresto to enalapril.
2) The PARADIGM-HF trial found Entresto reduced the risk of cardiovascular death or hospitalization for heart failure by 20% compared to enalapril.
3) Specifically, Entresto reduced the risk of cardiovascular death by 20% and first hospitalization for heart failure by 21% compared to enalapril.
Does Type of Dialysis Affect BNP in Fluid Overload Patients?Premier Publishers
Brain Natriuretic Peptide (BNP) levels are important as predictors of heart failure in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (PD). Twenty-four HD patients and 35 PD patients were included in the study. Each patient underwent an echocardiographic examination besides the determination of BNP, high-sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy). BNP, left ventricular mass (LVM), left ventricular mass index (LVMI) and Hcy levels were significantly higher in HD group (p<0.05); hs-CRP levels were significantly higher in PD group (p=0.029). Predialysis BNP was significantly higher than the postdialysis BNP (p=0.003). There was a significant correlation between LVMI and BNP in PD (r=0.527, p=0.009) and predialysis BNP in HD (r=0.417, p=0.043) groups. In conclusion, BNP levels were found to be significantly correlated with LVMI in HD and PD patients. Hemodialysis patients had higher BNP and LVMI levels. This may be due to the hemodynamic changes which occur with the hemodialysis.
Acute heart failure is a common entity and it's management is changing day by day.
Sacubitril valsartan is a novel medicine with mortality and morbidity benifits
Does Type of Dialysis Affect BNP in Fluid Overload Patients?Premier Publishers
Brain Natriuretic Peptide (BNP) levels are important as predictors of heart failure in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (PD). Twenty-four HD patients and 35 PD patients were included in the study. Each patient underwent an echocardiographic examination besides the determination of BNP, high-sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy). BNP, left ventricular mass (LVM), left ventricular mass index (LVMI) and Hcy levels were significantly higher in HD group (p<0.05); hs-CRP levels were significantly higher in PD group (p=0.029). Predialysis BNP was significantly higher than the postdialysis BNP (p=0.003). There was a significant correlation between LVMI and BNP in PD (r=0.527, p=0.009) and predialysis BNP in HD (r=0.417, p=0.043) groups. In conclusion, BNP levels were found to be significantly correlated with LVMI in HD and PD patients. Hemodialysis patients had higher BNP and LVMI levels. This may be due to the hemodynamic changes which occur with the hemodialysis.
Acute heart failure is a common entity and it's management is changing day by day.
Sacubitril valsartan is a novel medicine with mortality and morbidity benifits
Ponencia presentada por el Dr. Nicolás Manito Lorite en el directo online ‘Fármacos que mejoran el pronóstico cardiovascular’, realizado en la Casa del Corazón el 5 de junio de 2018
1. A Case report of Heart Failure
2. Discussion on Heart Failure
3. Role of Peptides in Heart Failure
4. Importance of 30 days in heart failure
5. Role of ENTRESTO in Stable Heart Failure patient (PARADIGM-HF study)(HFrEF)
6. Biomarkers in Heart Failure
7. Role of ARNI in Hospitalized Heart Failure patient (PIONEER-HF study)
8. Role of ARNI in HFpEF (PARAMOUNT Trial)
9. Safety and usefulness of ACEI/ARB/ARNI
10. Role of SGPL2 inhibitors in HF with/without DM
Venous Thromboembolism (VTE): Recent Advances in Reducing the Disease BurdenNBCA
The National Center on Birth Defects and Developmental Disabilities, Division of Blood Disorders, hosted an important webinar for health professionals on Thursday, November 6, 2014. During this webinar, Gary Raskob, PhD, Chair of NBCA’s Medical & Scientific Advisory Board, and Dean, College of Public Health, University of Oklahoma Health Science Center, reviewed the disease burden associated with DVT/PE, and discussed strategies to reduce this burden through prevention of both first time and recurrent clots.
Ponencia presentada por el Dr. Nicolás Manito Lorite en el directo online ‘Fármacos que mejoran el pronóstico cardiovascular’, realizado en la Casa del Corazón el 5 de junio de 2018
1. A Case report of Heart Failure
2. Discussion on Heart Failure
3. Role of Peptides in Heart Failure
4. Importance of 30 days in heart failure
5. Role of ENTRESTO in Stable Heart Failure patient (PARADIGM-HF study)(HFrEF)
6. Biomarkers in Heart Failure
7. Role of ARNI in Hospitalized Heart Failure patient (PIONEER-HF study)
8. Role of ARNI in HFpEF (PARAMOUNT Trial)
9. Safety and usefulness of ACEI/ARB/ARNI
10. Role of SGPL2 inhibitors in HF with/without DM
Venous Thromboembolism (VTE): Recent Advances in Reducing the Disease BurdenNBCA
The National Center on Birth Defects and Developmental Disabilities, Division of Blood Disorders, hosted an important webinar for health professionals on Thursday, November 6, 2014. During this webinar, Gary Raskob, PhD, Chair of NBCA’s Medical & Scientific Advisory Board, and Dean, College of Public Health, University of Oklahoma Health Science Center, reviewed the disease burden associated with DVT/PE, and discussed strategies to reduce this burden through prevention of both first time and recurrent clots.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...
Presentation 2 - Andrew Ludman_0_0.pptx
1. Dr Andrew Ludman
Cardiology Consultant
Royal Devon & Exeter NHS Foundation Trust
University of Exeter Medical School
a.ludman@nhs.net
2. Declarations
• Support for educational events: Astra Zenaca, Bayer, Boehringer
Ingelheim, Daiichi-Sankyo, Pfizer, Sanofi, Servier, Shire
• Speaker fees: Novartis, Sanofi, Astra Zenaca.
• Grant for HF service support: Servier
3.
4. What is heart failure?
• A structural cardiac abnormality leading to failure of the
heart to provide adequate oxygen to metabolising tissues
despite normal filling pressures.
• A syndrome in which patients have typical symptoms (e.g.
breathlessness, ankle swelling, and fatigue) and signs (e.g.
elevated jugular venous pressure, pulmonary crackles, and
displaced apex beat) resulting from an abnormality of cardiac
structure or function.
2012 ESC HF guidelines
‘Acute’ ‘Chronic’ ‘Hospitalised’ ‘De novo’ ‘Decompensated’ ‘Right’ ‘Left’
6. Global age standardised mortality rates by
sociodemographic index
Lancet 2017, 390;10110: pg1084-1150
7. Global number of deaths by cause 1990 - 2016
Lancet 2017, 390;10110: pg1151-1210
8. Leading causes of lost years of life
Lancet 2017, 390;10110: pg1151-1210
9. Projected increasing burden of common risk factors for
heart failure in the USA
Dunlay, S. M. et al. (2017) Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.65
11. Trends in incident HFpEF and
HFrEF in Olmsted County,
Minnesota, USA
Dunlay, S. M. et al. (2017) Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.65
Is heart failure incidence increasing?
Sex-standardized trends in incidence of
heart failure, by age group: Ontario,
Canada
Darwin F. Yeung et al. CMAJ 2012;184:E765-E773
12. CVD in the UK
BHF CVD Statistics Compendium 2017
13. Prevalence of HF in the UK
• ~550,000 people in the
UK with heart failure
BHF CVD Statistics Compendium 2017
QOF
0.8%
Bhatnager et al. 2014 Heart
16. Hospitalised Heart Failure in the UK – how are doing?
NICOR UK HF Audit 2015-16
Inpatient mortality ↓ to
8.9% from 9.6% (2014/15)
1 in 3 dead at 1 year
17. High hospital readmission rates
www.escardio.org/communities/HFA/Pages/global-heart-failure-awareness-programme.aspx
19. What can we do to improve outcomes?
NICE Quality Standard on Acute HF. 2015. Available at: https://www.nice.org.uk/guidance/qs103
Last accessed: Sept 2017.
20. Don’t miss the diagnosis – use serum natriuretic peptide testing
Griffin et al. 2017 Value In Health. In press Roberts et al. BMJ 2015
AHF QS 1. Adults presenting to hospital with new suspected acute heart failure
have a single measurement of natriuretic peptide.
21. AHF QS 2. Adults admitted to hospital with new suspected acute heart failure
and raised natriuretic peptide levels have a transthoracic Doppler 2D
echocardiogram within 48 hours of admission.
• Heart failure with reduced
ejection fraction (HFREF)
• Heart failure with preserved
ejection fraction (HFPEF)
22. Type of heart failure?
Heart failure with reduced ejection fraction
(HFREF)
Heart failure with preserved ejection fraction
(HFPEF)
23. AHF QS 3. Adults admitted to hospital with acute heart failure
have input within 24 hours of admission from a dedicated
specialist heart failure team
24. AHF QS 4. Adults with acute heart failure due to left ventricular systolic dysfunction
are started on, or continue with, beta-blocker treatment during their hospital
admission.
AHF QS5. Adults admitted to hospital with acute heart failure and reduced left
ventricular ejection fraction are offered an ACE inhibitor and an aldosterone
antagonist.
More drugs…better outcome
25. Discharge planning and specialist follow up reduce mortality
NICOR UK HF Audit 2015-16
AHF QS 6. Adults with acute heart failure have a follow-up clinical assessment by a
member of the community- or hospital-based specialist heart failure team within
2 weeks of hospital discharge.
27. Outcome for 1-year death or urgent heart transplantation (Tx) (left) and for the combined end point of 1-
year death, urgent heart transplantation, or heart failure (HF) readmission (right) for the patients subdivided
on the basis of the development of worsening renal function (WRF) and on the presence of signs of
congestion (Cong) at discharge.
Marco Metra et al. Circ Heart Fail. 2012;5:54-62
Don’t underestimate the importance of diuretics -
decongestion is really important
29. Sympatheticnervoussystem
Renin-angiotensin-aldosteronesystem
Vasoconstriction
Blood pressure
Sympathetic tone
Aldosterone
Hypertrophy
Fibrosis
Natriureticpeptidesystem
Vasodilation
Blood pressure
Sympathetic tone
Natriuresis/diuresis
Vasopressin
Aldosterone
Fibrosis
Hypertrophy
Vasoconstriction
RAAS activity
Vasopressin
Heart rate
Contractility
NPRs
Natriuretic
peptide
receptors
NPs
Natriuretic peptides
Epinephrine
(adrenaline)
Norepinephrine
(noradrenaline)
α1, β1, β2
receptors
Ang II AT1R
Neurohormonal activation in heart failure
Ang=angiotensin; AT1R=angiotensin II type 1 receptor; NPs=natriuretic peptides; NPRs=natriuretic peptide receptors; RAAS=renin-angiotensin-
aldosterone system.
1. Levin E, et al. N Engl J Med. 1998;339:321–8. 2. Nathisuwan S, Talbert RL. Pharmacotherapy. 2002;22:27–42.
3. Kemp CD, Conte JV. Cardiovascular Pathology. 2012;365–71. 4. Schrier RW, Abraham WT. N Engl J Med. 2009;341:577–85.
HF SYMPTOMS and PROGRESSION
30. Entresto (sacubitril/valsartan) simultaneously inhibits neprilysin (via
sacubitril) and blocks AT1 receptors (via valsartan)1–5
*Neprilysin substrates listed in order of relative affinity for NEP: ANP, CNP, Ang II, Ang I, adrenomedullin, substance P, bradykinin, endothelin-1,
BNP.
Ang=angiotensin; ANP=atrial natriuretic peptide; AT1=angiotensin II type 1; BNP=brain natriuretic peptide; CNP=C-type natriuretic peptide.
1. Levin E, et al. N Engl J Med 1998;339:321–8. 2. Nathisuwan and Talbert. Pharmacotherapy. 2002;22:27–42.3. Schrier and
Abraham. N Engl J Med. 1999;341:577–85. 4. Langenickel TH, Dole WP. Drug Discov Today: Ther Strateg. 2012;9:e131–9.
5. Feng et al. Tetrahedron Letters. 2012;53:275–6.
31. PARADIGM-HF: Design
RANDOMISATION
n=8442
2 Weeks 1–2 Weeks 2–4 Weeks
SINGLE-BLIND ACTIVE
RUN-IN PERIOD
DOUBLE-BLIND
TREATMENT PERIOD
On top of standard HFrEF therapy (excluding ACEIs and ARBs)
Median of 27 months’ follow-up
Sacubitril/
valsartan
200 mg BID‡
Sacubitril/
valsartan
100 mg BID†
Enalapril
10 mg BID*
Enalapril 10 mg BID§
Sacubitril/valsartan 200 mg BID‡
Randomised, double-blind trial with a single-blind run-in period1–3
*Enalapril 5 mg BID (10 mg TDD) for 1–2 weeks followed by enalapril 10 mg BID (20 mg TDD) as an optional starting run-in dose for those patients who are treated
with ARBs or with a low dose of ACEI; †200 mg TDD; ‡400 mg TDD; §20 mg TDD. BID=twice daily; TDD=total daily dose.
1. McMurray J, et al. Eur J Heart Fail. 2013;15:1062–73.
2. McMurray J, et al. Eur J Heart Fail. 2014;16:817–25.
3. McMurray J, et al. N Engl J Med. 2014; 371:993–1004.
32. PARADIGM-HF: Primary endpoint
Death from CV causes or first hospitalisation for HF1,2
249
236
896
853
1544
1488
2257
2123
3018
2922
3663
3579
3922
3883
4187
4212
Days since randomisation
1.0
0.6
0.4
0.2
0
0 180 360 540 720 900 1080 1260
Cumulative
probability
21.8% (Entresto) vs. 26.5% (Enalapril)
Hazard ratio=0.80 (95% CI: 0.73–0.87)
p<0.0000002;2 ARR=4.7%; NNT=21.*
No. at risk
Entresto
(sacubitril/valsartan):
Enalapril:
Enalapril
Entresto (sacubitril/valsartan)
ARR=absolute risk reduction NNT=numbers needed to treat . *Events rates, ARR and NNT are all based on median F/U at 27 months.
1. McMurray J, et al. N Engl J Med. 2014;371(11): 993-1004.
2. Entresto Summary of Product Characteristics.
33. PARADIGM-HF: Components of primary endpoint
Death from CV causes1
280
279
1005
994
1716
1726
2478
2410
3282
3231
3891
3860
4056
4051
4187
4212
Days since randomisation
1.0
0.6
0.4
0.2
0
0 180 360 540 720 900 1080 1260
Cumulative
probability
13.3% (Entresto) vs. 16.5% (Enalapril)
Hazard ratio=0.80 (95% CI: 0.71–0.89)
p<0.001; ARR=3.2%; NNT=32.*
Enalapril
Entresto (sacubitril/valsartan)
ARR=absolute risk reduction NNT=numbers needed to treat. *Events rates, ARR and NNT are all based on median F/U at 27 months.
1. McMurray J, et al. N Engl J Med. 2014;371(11): 993-1004.
No. at risk
Entresto
(sacubitril/valsartan):
Enalapril:
34. PARADIGM-HF: Components of primary endpoint
First hospitalisation for HF1
249
236
896
853
1544
1488
2257
2123
3018
2922
3663
3579
3922
3883
4187
4212
Days since randomisation
1.0
0.6
0.4
0.2
0
0 180 360 540 720 900 1080 1260
Cumulative
probability
12.8% (Entresto) vs. 15.6% (Enalapril)
Hazard ratio=0.79 (95% CI: 0.71–0.89)
p<0.001; ARR=2.8%; NNT=36.*
Enalapril
Entresto (sacubitril/valsartan)
ARR=absolute risk reduction NNT=numbers needed to treat. *Events rates, ARR and NNT are all based on median F/U at 27 months.
1. McMurray J, et al. N Engl J Med. 2014;371(11): 993-1004.
No. at risk
Entresto
(sacubitril/valsartan):
Enalapril:
35. Time to first hospitalisation for HF reduced within 30 days of
randomisation1,2*
1.5
1.0
0.5
0
0 10 20 30
Kaplan-Meier
estimate
of
Cumulative
rate
Enalapril
Entresto (sacubitril/valsartan)
4140
4143
4153
4166
4174
4192
4187
4212
Time since randomisation (days)
Hazard ratio=0.60 (95% CI: 0.38-0.94)
p=0.027; ARR=0.5%
No. at risk
Entresto
(sacubitril/valsartan):
Enalapril:
1. Packer M, et al. Circulation. 2015;131(1):54-61.
2. Entresto Summary of Product Characteristics
3. Novartis Data on file. [LCZ15-C025-1128] October 2015
*ARR=absolute risk reduction (at median F/U 30 days).
Time to first hospitalisation was not a primary or secondary endpoint in PARADIGM-HF.
36. Entresto demonstrated significant clinical benefits
vs enalapril:
• 20% reduced risk of CV death or first HF hospitalisation (ARR=4.7%)
• 20% reduced risk of CV mortality (ARR=3.2%)
• 21% reduced risk of first HF hospitalisation (ARR=2.8%)
• Fewer HF symptoms and a better quality of life*
PARADIGM-HF: Summary of efficacy results1,2
ARR=absolute risk reduction (at median F/U 27 months). *According to analysis from the KCCQ sub-domains.
ARR=absolute Risk Reduction; CV=cardiovascular KCCQ=Kansas City Cardiomyopathy Questionnaire.
1. McMurray J, et al. N Engl J Med. 2014;371:993–1004.
2. Packer M, et al. Circulation 2015;131:54–61
37. PARADIGM-HF: Fewer adverse events leading to
permanent study drug discontinuation
McMurray et al. N Engl J Med 2014;371:993–1004.
10.7%
0.9% 0.7% 0.3%
12.3%
0.7%
1.4%
0.4%
0%
5%
10%
15%
Any adverse event Hypotension Renal impairment Hyperkalaemia
Patients
who
discontinued
study
drug
(%)
Entresto (sacubitril/valsartan;
N=4187)
Enalapril (N=4212)
p=0.03
p=0.38 p=0.002
p=0.56
n=10 n=5
38. NICE Technology Appraisal Guidance (TA388):
Sacubitril/valsartan is recommended as an option for treating people
with HF with reduced ejection fraction, only in people:1
NICE has reviewed sacubitril/valsartan (Entresto)
with NYHA class II to IV chronic heart failure and
who are already taking a stable dose of ACEI or ARBs and
with a left ventricular ejection fraction of 35% or less
ACEI=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; NYHA=New York Heart Association.
1. NICE Technology Appraisal Guidance (TA388). Appraisal consultation document. Sacubitril valsartan for treating symptomatic
chronic heart failure with reduced ejection fraction. April 2016 Available at: https://www.nice.org.uk/guidance/ta388 Last accessed
27 April 2016
39. NICE Technology Appraisal Guidance recommends that:
NICE TAG Recommendation
1. NICE Technology Appraisal Guidance (TA388). Sacubitril valsartan for treating symptomatic chronic heart failure with reduced ejection
fraction. April 2016 Available at: https://www.nice.org.uk/guidance/ta388 Last accessed 27 April 2016
2. NICE. Chronic HF Guideline. August 2010 Available at: https://www.nice.org.uk/guidance/cg108 Last accessed 27 April 2016
Treatment with sacubitril/valsartan should be started by a heart
failure specialist with access to a multidisciplinary heart failure team1
Dose titration and monitoring should be performed by the most
appropriate team member as defined in NICE’s guideline on chronic
heart failure in adults2
40. Where next for sacubitril/valsartan?
• Hospitalised/Acute heart failure
• Starting directly (no ACE-I)
• HF PEF
• Hypertension
• …..
41. Another new trick?
Sodium glucose co-transporter 2 (SGLT2) inhibitors
Singh 2014 - DOI: 10.4103/0975-9727.135761 Zinman B et al. N Engl J Med 2015;373:2117-2128
42. Sodium glucose co-transporter 2 (SGLT2) inhibitors
EMPA REG outcomes
Zinman B et al. N Engl J Med 2015;373:2117-2128
43. Sodium glucose co-transporter 2 (SGLT2) inhibitors
EMPA REG outcomes
Zinman B et al. N Engl J Med 2015;373:2117-2128
44. Conclusions
• Not sure about the HF epidemic yet
• Outcomes for hospitalised patients are improving
but remain poor
• Optimise fluid balance and medication pre-
discharge
• Specialist involvement and follow up
• Active drug development – watch this space