1. Heart failure is a major public health problem, affecting over 5 million Americans. It is primarily a condition of the elderly and costs Medicare billions of dollars annually.
2. The VALIANT trial compared the ARB valsartan to the ACE inhibitor captopril and their combination in over 14,000 patients with heart failure or left ventricular dysfunction following a myocardial infarction. It found valsartan to be noninferior to captopril in reducing cardiovascular mortality and morbidity.
3. The presentation discusses the role of the renin-angiotensin system in cardiovascular disease and how ARBs like valsartan can provide beneficial blockade of this system in heart failure and post-myocardial infarction
ONTARGET trial - Summary & Results with Ramipril Global Endpointtheheart.org
A study to test whether an ARB (which blocks the effects of angiotensin II without enhancing bradykinin) was similarly effective to an ACE inhibitor and whether the combination of an ACE inhibitor and an ARB may be superior
A review of the existing evidence that supports the current practice in perioperative medicine regarding Renin-angiotensin-aldosterone system antagonists, mainly ACE inhibitors and Angiotensin type 1 receptor blockers (ARB's).
Presented as the Cleveland Clinic Hospital Medicine Grand Rounds on April 1, 2009. CME AMA Category 1 - 1 hour.
ONTARGET trial - Summary & Results with Ramipril Global Endpointtheheart.org
A study to test whether an ARB (which blocks the effects of angiotensin II without enhancing bradykinin) was similarly effective to an ACE inhibitor and whether the combination of an ACE inhibitor and an ARB may be superior
A review of the existing evidence that supports the current practice in perioperative medicine regarding Renin-angiotensin-aldosterone system antagonists, mainly ACE inhibitors and Angiotensin type 1 receptor blockers (ARB's).
Presented as the Cleveland Clinic Hospital Medicine Grand Rounds on April 1, 2009. CME AMA Category 1 - 1 hour.
Although many are still concerned with an ARB–MI paradox, our study of close to 60 000 patients with MI should serve as reassurance that ARBs are not associated with adverse outcomes compared with ACEIs. Potential benefits of ARBs as compared with ACEIs in older women with MI should be further evaluated.
http://www.theheart.org/web_slides/1225165.do
A randomized study on Olmesartan and Calcium Antagonists Randomized (OSCAR) using high-dose of olmesartan or standard dose calcium-channel blocker (CCB) (amlodipine or azelnidipine) with patients with uncontrolled hypertension
Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms.
Presented at AHA by: Faiez Zannad, M.D., Ph.D., John J.V. McMurray, M.D., Henry Krum, M.B., PhD., Dirk J. van Veldhuisen, M.D.,Ph.D., Karl Swedberg, M.D., Ph.D, Harry Shi, M.S., John Vincent, M.B., PhD., Stuart J Pocock, Ph.D. and Bertram Pitt, M.D. for the EMPHASIS-HF Study Group * Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure
Courtesy of http://www.cardiovascularbusiness.com
Secondary Prevention after ACS: Focused on Anticoagulant TherapyPERKI Pekanbaru
Dr. Nathania Marliani Kristanti, SpJP, FIHA. 3rd Pekanbaru Cardiology Update, August 25th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com
ARBs (Angiotensin receptor blockers) are the most widely used anti hypertensive throughout the world. A solid knowledge related to ARB will make our practice more patients friendly & benefit will be maximum.
Although many are still concerned with an ARB–MI paradox, our study of close to 60 000 patients with MI should serve as reassurance that ARBs are not associated with adverse outcomes compared with ACEIs. Potential benefits of ARBs as compared with ACEIs in older women with MI should be further evaluated.
http://www.theheart.org/web_slides/1225165.do
A randomized study on Olmesartan and Calcium Antagonists Randomized (OSCAR) using high-dose of olmesartan or standard dose calcium-channel blocker (CCB) (amlodipine or azelnidipine) with patients with uncontrolled hypertension
Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms.
Presented at AHA by: Faiez Zannad, M.D., Ph.D., John J.V. McMurray, M.D., Henry Krum, M.B., PhD., Dirk J. van Veldhuisen, M.D.,Ph.D., Karl Swedberg, M.D., Ph.D, Harry Shi, M.S., John Vincent, M.B., PhD., Stuart J Pocock, Ph.D. and Bertram Pitt, M.D. for the EMPHASIS-HF Study Group * Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure
Courtesy of http://www.cardiovascularbusiness.com
Secondary Prevention after ACS: Focused on Anticoagulant TherapyPERKI Pekanbaru
Dr. Nathania Marliani Kristanti, SpJP, FIHA. 3rd Pekanbaru Cardiology Update, August 25th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com
ARBs (Angiotensin receptor blockers) are the most widely used anti hypertensive throughout the world. A solid knowledge related to ARB will make our practice more patients friendly & benefit will be maximum.
Sacubitrilo / Valsartán (Entresto®), nueva opción terapéutica en IC con FE reducida
28/09/2016 18:00h Casa del Corazón, Madrid
http://entresto.secardiologia.es
#entresto
De la evidencia científica a las recomendaciones clínicas
Dr. Josep Comín Colet, Hospital del Mar (Barcelona)
@JosepComin
Valzaar (Valsartan Tablets), an angiotensin II receptor blocker (ARB) is used to treat patients after a recent heart attack, to treat heart failure and to treat high blood pressure.
Prevention of recurrent stroke in atrial fibrillation Jacek StaszewskiJacek Staszewski
Prevention of recurrent stroke in atrial fibrillation. Comaprison of NOAC vs VKA. Riks of hemorrhagic stroke. When anticoagulation should be initiated following acute stroke.
Dabigatran for Atrial Fibrillation: Cardioversion and Ablationlarriva
The presentation covers background information regarding atrial fibrillation (A-fib) and the use of oral anticoagulant dabigatran surrounding cardioversion and ablation for A-fib. The information surrounds a patient case in which the patient prefers dabigatran over warfarin. Available literature on the topic is analyzed to make a patient specific recommendation.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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.
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.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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!
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
How STIs Influence the Development of Pelvic Inflammatory Disease.pptx
ueda2011 hf to mi -d.samer sayed
1. 1
From Myocardial Infarction to
Heart Failure
And
Use of ARBs
Prof Samir Abd Elkader
Professor of cardiology
Assuit University
2. 2
Heart Failure is a Major and Growing Public
Health Problem in the U.S.
• Approximately 5 million patients in this country have
HF
• Over 550,000 patients are diagnosed with HF for the
first time each year
• Primary reason for 12 to 15 million office visits and
6.5 million hospital days each year
• In 2001, nearly 53,000 patients died of HF as a
primary cause
3. 3
Heart Failure is Primarily a
Condition of the Elderly
• The incidence of HF approaches 10 per 1000
population after age 65
• HF is the most common Medicare diagnosis-
related group
• More dollars are spent for the diagnosis and
treatment of HF than any other diagnosis by
Medicare
4. 4
Definition of Heart Failure
HF is a complex clinical syndrome that can
result from any structural or functional
cardiac disorder that impairs the ability of
the ventricle to fill with or eject blood.
5. 5
“Heart Failure” vs. “Congestive Heart Failure”
Because not all patients have volume overload at
the time of initial or subsequent evaluation, the
term “heart failure” is preferred over the older
term “congestive heart failure.”
7. 7
Stages of Heart Failure
At Risk for Heart Failure:
STAGE A High risk for developing HF
STAGE B Asymptomatic LV dysfunction
Heart Failure:
STAGE C Past or current symptoms of HF
STAGE D End-stage HF
10. Adapted from Dzau V, Braunwald E. Am Heart J. 1991;121:1244-1263.
Risk factors
Diabetes, hypertension
Atherosclerosis
and LVH
Myocardial
infarction
Remodeling
Ventricular
dilation
Heart failure
End-stage
heart disease
Death
The Cardiovascular Continuum
11. Effects of A II at ATEffects of A II at AT11 and ATand AT22 ReceptorsReceptors
Sensitive to blockade
by ARBs
AT2AT1
Vasoconstriction
Aldosterone release
Oxidative stress
Vasopressin release
SNS activation
Inhibits renin release
Renal Na+
& H2O reabsorption
Cell growth & proliferation
Vasodilation
Antiproliferation
Apoptosis
Antidiuresis/antinatriuresis
Bradykinin production
NO release
Siragy H. Am J Cardiol. 1999;84:3S-8S.
12. *P <0.001 vs placebo.
Adapted with permission from Biollaz J et al. J Cardiovasc Pharmacol. 1982;4:966-972.
A II Escape With
Long-Term ACE-I Therapy
PlasmaACE,
nmol/mL/min
100
80
60
40
20
0
*
* * * * * * *
30
20
10
0
PlasmaAII,
pg/mL
*
Placebo 4 h 24 h 1 2 3 4 5 6
Hospital Months
Plasma A II levels increased with
time, although plasma-converting
enzyme activity remained suppressed
(n = 9 after 24 h)
16. 1.0
0.9
0.8
0.6
13.2% risk reduction
p= 0.009
Significant benefits on combined
mortality / morbidity endpoint
0
Event-freeprobability
Placebo
Valsartan
3 6 9 12 211815 24 27
Time since randomization (months)
0.7
Cohn et al. NEJM 2001 345:1667
17. Reduction in Mortality with Valsartan
(No ACEI Subgroup)
50
100
0 3 6 9 12 15 18 21 24 27 30
Valsartan
(N = 185)
ProportionSurvived
(%)
P value (log-rank) = .0171
60
70
80
90
Placebo
(N = 181)
Time Since Randomization (months)
Risk reduction= 33.1%
Hazard ratio (Cox model): 0.6694
(Adapted from Maggioni AP, et al. [abstract 839-5]. J Am Coll Cardiol. 2002)
18. Reduction in Combined Morbidity Endpoint* with
Valsartan
(No ACEI Subgroup)
Event-FreeProbability
Time Since Randomization (months)
Hazard ratio (Cox model) : 0.560
*First morbid event, including death or hospitalization
40
50
60
70
80
90
100
0 3 6 9 12 15 18 21 24 27 30
P value (log-rank) = .0002
Valsartan
(N = 185)
Placebo
(N = 181)
Risk reduction = 44.0%
(Adapted from Maggioni AP, et al. [abstract 839-5]. J Am Coll Cardiol. 2002)
19. Val-HeFT impact on FDA
•Valsartan is also approved by Egypt MOH for treatment
of Heart Failure.
•So, Valsatan is the first & ONLY ARB approved in HF
20. Adapted from Dzau V, Braunwald E. Am Heart J. 1991;121:1244-1263.
Risk factors
Diabetes, hypertension
Atherosclerosis
and LVH
Myocardial
infarction
Remodeling
Ventricular
dilation
Heart failure
End-stage
heart disease
Death
From AMI to HF
Valsartan has a definite role
with proven Cardiac Protection
21. Inhibition of theInhibition of the
ReninReninAngiotensin SystemAngiotensin System
in Cardiovascular Diseasein Cardiovascular Disease
23. Unacceptable High Mortality Rate from
Acute Heart Attack
1- Under utilization of drug treatment is a major
Factor in the unaccepted high Post- Heart Attack.
2-Many patients taking ACE inhibitors suffer intolerable side
Effects such as dry irritant cough &1st
dose hypotension.
3-Proper Blockade of ACE & non ACE Pathways.
24. Rational
VALIANT : was designed as a mortality trial in high-risk MI
patients (SAVE, AIRE, TRACE) who derived
particular benefits from an ACE inhibitor.
To determine whether:
•the ARB valsartan was superior to captopril in improving
survival
and with equal statistical power
•the addition of the ARB valsartan to captopril was superior to
the proven dose of captopril in improving survival
25. VALIANT: Endpoints
Primary Endpoints
Time to all-cause mortality
–Cardiovascular mortality
–Cardiovascular mortality, reinfarction,
and hospitalization for heart failure
–Cardiovascular mortality, reinfarction,
hospitalization for heart failure,
resuscitated sudden death, stroke
Secondary Endpoints
Am Heart J. 2000;140:727–734.
26. Captopril
4909
4871 (99.2%)
Vital status
unknown:
38 (0.8%)
Enrollment and Follow-up
Median follow-up: 24.7 months
Valsartan
4909
4856 (98.9%)
Vital status
unknown:
53 (1.1%)
14,808 Patients Randomized
4837 (99.0%)
Vital status
unknown:
48 (1.0%)
Combination
4885
Informed consent
not ensured: 105 patients
14,703 Patients
13
27. Cap 6.25 mg
Val 20 mg
Cap 12.5 mg
Val 20 mg
Cap 25 mg
Val 40 mg
Cap 50 mg (tid)
Val 80 mg (bid)
COMBINATION
Cap 6.25 mg
Cap 12.5 mg
Cap 25 mg
Cap 50 mg (tid)
CAPTOPRIL (tid)
Val 20 mg
Val 40 mg
Val 80 mg
Val 160 mg (bid)
VALSARTAN (bid)
Step I
GOAL by 3 months
Step IVStep IIIStep II
Study Drug
Dose Titration
Am Heart J. 2000;140:727–734.
28. Lancet. 2002;360:752–760. Am J Cardiol. 1991;68:70D–79D. Lancet. 1993;342:821–828.
N Engl J Med. 1995;333:1670–1676. Data on file. Novartis Pharmaceuticals.
SAVE AIRE TRACE OPTIMAAL VALIANT
2,231 1,986 1,749
5,477
14,703
0
2,000
4,000
6,000
8,000
10,000
16,000
12,000
14,000
VALIANT: B- Largest Population
29. 24 Countries. 931 Sites. 14,703 Patients.
Europe:
5163
Australia/
New Zealand:
443
Brazil and
Argentina:
848
South
Africa:
58
Russia:
3135Canada:
1092
USA:
3964
31. Captopril
25% Reduction in Mortality
Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349
Months
Valsartan vs. Captopril: HR = 0.96; P = 0.198
Valsartan + Captopril vs. Captopril: HR = 0.97; P = 0.369
0
0.1
0.2
0.3
0.4
0 6 12 18 24 30 36
ProbabilityofEvent
Valsartan
Valsartan + Captopril
32. Noninferior
ityVal Superior
to Cap
Cap Superior
to Val
Noninferiorit
y not
Demonstrate
d
Cardiovascular
Mortality and Morbidity
0.8 1 1.2
Hazard Ratio
(97.5% CI)
1.13
P-value
(noninferiority)
noninferiority
margin
CV Death
(1657 events)
0.001
CV Death or HF
(2661 events)
0.0001
CV Death or MI
(2234 events)
0.00001
CV Death,
MI, or HF
(3096 events)
0.000001
Favors Valsartan Favors Captopril
33. Captopril
0
0.1
0.2
0.3
0.4
0 6 12 18 24 30 36
Months
ProbabilityofEvent
Study Drug
Discontinuation
Overall
Due to
Adverse
Events
*P < 0.05 vs Captopril
Valsartan + Captopril
*
*
Valsartan
*
34. In patients with MI complicated by heart failure, left
ventricular dysfunction or both:
•25% Reduction in Mortality
Implications:
Tareg approved now MRP & in more 50 countries
As First line Treatment in Acute M.I
Conclusion
35.
36. Tareg is The First & The
Only ARB approved in H.F
and Acute M.I
The presence of AT1 and AT2 receptors has been documented in various tissues. The function of the AT2 receptors is currently under investigation; however, A II stimulation of the AT2 receptor is believed to counterbalance deleterious effects of AT1 receptor stimulation on the blood vessels, kidneys, and adrenals.1
Effects of AT1 receptor stimulation include vasoconstriction, cell growth and proliferation, angiogenesis, renal sodium reabsorption, secretion of aldosterone and vasopressin, and sympathetic activation.2
Effects of AT2 receptor stimulation include vasodilation, antiproliferation, apoptosis, differentiation, and regeneration.2
References:
1. Siragy HM. The role of the AT2 receptor in hypertension. Am J Hypertens. 2000;13:62S–67S.
2. Siragy H. Angiotensin II receptor blockers: review of the binding characteristics. Am J
Cardiol. 1999;84:3S–8S.
Message: In Val-HeFT, valsartan was added to usual heart-failure therapy.
Message: Adding valsartan to usual therapy, including ACE inhibitors, led to a statistically significant 13% reduction in the combined endpoint all-cause mortality and morbidity.
The objective of this slide set is to provide insight to the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial design. VALIANT is the first trial to compare the combination of an ACE inhibitor (ACEI) and an angiotensin receptor blocker (ARB) to a proven ACEI on mortality in patients with clinical heart failure (HF) and/or substantial left ventricular systolic dysfunction (LVSD) after acute myocardial infarction (MI).
VALIANT was designed as a mortality trial in high-risk MI patients who derived particular benefits from an ACE inhibitor (SAVE, AIRE, TRACE). To determine whether, the ARB valsartan was superior to captopril in improving survival, and, with equal statistical power, to determine whether, the addition of the ARB valsartan to captopril was superior to the proven dose of captopril in improving survival.
If valsartan was not superior to captopril, a non-inferiority analysis was prespecified to determine whether valsartan could be considered “as effective as” captopril in improving survival.
Am Heart J;2000;140:727-734
The primary efficacy parameter of VALIANT is all-cause mortality (time to death). An important secondary efficacy parameter is the composite of cardiovascular death or reinfarction or hospitalization for new or worsening HF. Other secondary endpoints will provide a more complete picture of the relative efficacy of the therapeutic regimens being tested.
An endpoints committee, blinded to treatment assignments, will adjudicate deaths, recurrent nonfatal MIs, and hospitalizations for HF by predefined criteria.1
VALIANT will also address quality of life and pharmacoeconomic issues, and will assess safety and tolerability of the treatment arms.
Reference:
1. Pfeffer MA, McMurray J, Leizorovicz A, et al. Valsartan in acute myocardial infarction trial (VALIANT): rationale and design. Am Heart J. 2000;140:727–750.
14,703 patients randomized and consented. Vital status was ascertained in just over 99% and was even in all 3 groups. Median follow-up 24.7 months. Vital status known similar in all 3 groups.
The dose titration regimen for captopril mirrored that used in SAVE, starting with 6.25 mg titrating in four steps to 50 mg t.i.d. The valsartan arm titrated from 20 mg to 160 twice a day (the dose used in the Val-HeFT study). The combination arm in VALIANT is unique in that the ARB valsartan was added from 20 to 80 mg twice daily to a proven effective regimen of an ACE inhibitor
Am Heart J;2000;140:727-734
The landmark post-MI trials SAVE, AIRE, and TRACE, which clearly established the benefits of long-term ACE inhibition therapy in high-risk post-MI patients, each enrolled approximately 2,000 patients, with SAVE enrolling over 2,200 as the largest.1–3 OPTIMAAL, which compared the ARB losartan to the ACEI captopril in post-MI patients, recruited over 5,000 patients.4
VALIANT is the largest trial with ARBs and the only one powered to assess combined blockade (ARB + ACEI) of the RAS vs ACEI therapy alone.5
References:
1. Moye LA, Pfeffer MA, Braunwald E. Rationale, design and baseline characteristics of the survival and ventricular enlargement trial. SAVE Investigators. Am J Cardiol. 1991;68:70D–79D.
2. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet. 1993;342:821–828.
3. Køber L, Torp-Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting–enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1995;333:1670–1676.
5. Data on file. Novartis Pharmaceuticals Corporation. East Hanover, NJ, USA.
4. Dickstein K, Kjekshus J, OPTIMAAL Steering Committee of the OPTIMAAL Study Group. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Lancet. 2002;360:752–760.
VALIANT was truly an international study conducted in 24 countries with 931 participating sites that randomized the 14,703 patients.
Since ACE inhibitors have been shown to reduce the risk of heart failure admissions and nonfatal MIs, as well as death, we compared the hazard ratios for this composite event of the valsartan groups to the proven captopril regimen. The event rate for the valsartan monotherapy group was similar to captopril with a hazard ratio of 0.96. The combination of valsartan plus captopril was also no different than captopril alone with a hazard ratio of 0.97.
Pfeffer, et al., NEJM 2003;349:1893-1906
The effects of valsartan relative to captopril were compared for a hierarchy of cardiovascular events. For each of the CV fatal and nonfatal composites, the point estimates favored valsartan and, importantly, the lower limit of the 97.5% confidence intervals were well within the non- inferiority range. Specifically, with over 3000 composite events, the hazard ratio and confidence intervals for valsartan relative to captopril demonstrates that all of these cardiovascular benefits of captopril were preserved in the valsartan group. (UCL fpr valsartan vs captopril- one-sided
1.075 for CV mortality, 1.024 for composite of CVM + MI + HF)
Pfeffer, et al., NEJM 2003;349:1893-1906
Discontinuation of study medications increased as a function of time in all groups. Relative to captopril patients, the valsartan group was less likely to discontinue due to an adverse event attributed to study medication. In contrast, those on the combination therapies were more likely to discontinue their study medication and more likely to experience study drug-related reasons for this discontinuation.
In patients with MI complicated by heart failure, left ventricular dysfunction or both,
valsartan is as effective as a proven dose of captopril in reducing the risk of:
Death, CV death, or nonfatal MI, or hospital admission for heart failure.
Combining valsartan with a proven dose of captopril produced no further reductions in mortality and resulted in more adverse drug events.
Implications are that by preserving all the cardiovascular benefits of an ACE inhibitor in this population, valsartan is a clinically effective alternative for high risk patients post-MI.