This study compared the 24-hour blood pressure lowering effects of sacubitril/valsartan versus olmesartan in Japanese patients with essential hypertension. The key findings were:
1) Sacubitril/valsartan produced greater reductions in 24-hour, daytime, and nighttime ambulatory blood pressure compared to olmesartan over 8 weeks.
2) A higher proportion of patients treated with sacubitril/valsartan achieved at least a 5 mmHg reduction in blood pressure.
3) Sacubitril/valsartan was more effective at reducing nighttime blood pressure in "nondipper" patients whose blood pressure does not normally decrease at night
Hypertension is a major concern & dreaded complication. It is known as the silent killer and responsible for a large number of cardiovascular morbidity and mortality. There are many antihypertensive drugs . Calcium channel blockers were the oldest one and widely used in the management. Azeldipine is the recent addition to this.
Hypertension is a major concern & dreaded complication. It is known as the silent killer and responsible for a large number of cardiovascular morbidity and mortality. There are many antihypertensive drugs . Calcium channel blockers were the oldest one and widely used in the management. Azeldipine is the recent addition to this.
Recent Advancements in the treatment of Hypertension.Akshata Darandale
Uncontrolled blood pressure had become most common cause of death accounting for more than 7 million deaths per year worldwide. Despite the availability of potent lifestyle and pharmacologic approaches, rates of control of blood pressure are unsatisfactory and additional strategies to curb the burden of hypertension are warranted. Several novel pharmacological and device-based approaches have recently been tested and may prove helpful to achieve better blood pressure control rates and thereby improve cardiovascular outcomes in patients with hypertension.
Vymada Tablet (ARNI: Angiotensin Receptor Neprilysin Inhibitor) is an anti-hypertensive drug used in combination with Sacubitril & Valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
We aimed to investigate the potential effects of fi x-dose atorvastatin plus amlodipine treatment and amlodipine alone treatment for 24 weeks on blood pressure, arterial stiffness and endothelial function in patients with hypertension and hypercholesterolemia. In a single-blinded, randomized, placebo-controlled and parallel design, 60 hypertensive and hypercholesterolemic patients were allocated to receive atorvastatin 10 mg/day plus amlodipine 5 mg/day or amlodipine 5 mg/day for 24 weeks. Central blood pressure was reduced significantly greater in atorvastatin plus amlodipine group than in amlodipine group after 12 and 24 weeks’ treatment. Both amlodipine and atorvastatin plus amlodipine therapy signifi cantly improved Flow-Mediated Dilation (FMD) compared to baseline (p < 0.01), the effect of atorvastatin plus amlodipine therapy was even greater after 24 weeks(p < 0.05). Atorvastatin plus amlodipine therapy signifi cantly decreased Heart Rate-Adjusted Augmentation Index (AIx@HR75), carotid-femoral and brachial-ankle Pulse Wave Velocity (PWV) when compared with baseline in both 12 weeks and 24 weeks’ administration, while amlodipine therapy not. FMD improvement was independently correlated with change in TC (β = -0.416, P = 0.004), while arterial stiffness improvement assessed with AIx@HR75 and baPWV, was correlated with change in central SBP (β = 0.772, P < 0.001, and β = 0.420, P = 0.003, respectively) in multivariate linear stepwise model. Fixed-dose amlodipine and atorvastatin treatment for 24 weeks reduced central BP and arterial stiffness, improved endothelial function greater than amlodipine therapy. Our findings suggested decrease in TC was the independent protective factor for endothelial function improvement and decrease in central SBP was the independent protective factor for arterial stiffness reduction during the follow-up period.
Angiotensin neprilysin inhibition in acute decompensated heart failureShadab Ahmad
Sacubitril–valsartan is an angiotensin receptor– neprilysin inhibitor that is indicated for the treatment of patients with symptomatic heart failure with reduced ejection fraction
Recent Advancements in the treatment of Hypertension.Akshata Darandale
Uncontrolled blood pressure had become most common cause of death accounting for more than 7 million deaths per year worldwide. Despite the availability of potent lifestyle and pharmacologic approaches, rates of control of blood pressure are unsatisfactory and additional strategies to curb the burden of hypertension are warranted. Several novel pharmacological and device-based approaches have recently been tested and may prove helpful to achieve better blood pressure control rates and thereby improve cardiovascular outcomes in patients with hypertension.
Vymada Tablet (ARNI: Angiotensin Receptor Neprilysin Inhibitor) is an anti-hypertensive drug used in combination with Sacubitril & Valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
We aimed to investigate the potential effects of fi x-dose atorvastatin plus amlodipine treatment and amlodipine alone treatment for 24 weeks on blood pressure, arterial stiffness and endothelial function in patients with hypertension and hypercholesterolemia. In a single-blinded, randomized, placebo-controlled and parallel design, 60 hypertensive and hypercholesterolemic patients were allocated to receive atorvastatin 10 mg/day plus amlodipine 5 mg/day or amlodipine 5 mg/day for 24 weeks. Central blood pressure was reduced significantly greater in atorvastatin plus amlodipine group than in amlodipine group after 12 and 24 weeks’ treatment. Both amlodipine and atorvastatin plus amlodipine therapy signifi cantly improved Flow-Mediated Dilation (FMD) compared to baseline (p < 0.01), the effect of atorvastatin plus amlodipine therapy was even greater after 24 weeks(p < 0.05). Atorvastatin plus amlodipine therapy signifi cantly decreased Heart Rate-Adjusted Augmentation Index (AIx@HR75), carotid-femoral and brachial-ankle Pulse Wave Velocity (PWV) when compared with baseline in both 12 weeks and 24 weeks’ administration, while amlodipine therapy not. FMD improvement was independently correlated with change in TC (β = -0.416, P = 0.004), while arterial stiffness improvement assessed with AIx@HR75 and baPWV, was correlated with change in central SBP (β = 0.772, P < 0.001, and β = 0.420, P = 0.003, respectively) in multivariate linear stepwise model. Fixed-dose amlodipine and atorvastatin treatment for 24 weeks reduced central BP and arterial stiffness, improved endothelial function greater than amlodipine therapy. Our findings suggested decrease in TC was the independent protective factor for endothelial function improvement and decrease in central SBP was the independent protective factor for arterial stiffness reduction during the follow-up period.
Angiotensin neprilysin inhibition in acute decompensated heart failureShadab Ahmad
Sacubitril–valsartan is an angiotensin receptor– neprilysin inhibitor that is indicated for the treatment of patients with symptomatic heart failure with reduced ejection fraction
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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
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
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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.
3. Blood-pressure reduction study using
LCZ696(ARNi), a novel dual-acting inhibitor.
Involved individuals with uncomplicated mild-to-moderate essential hypertension.
For patients following an antihypertensive washout, mean sitting diastolic blood pressure needed to be in
the range of 90–109 mm Hg.
Untreated patients had to exhibit a mean sitting diastolic blood pressure of 95–109 mm Hg to be considered
eligible.
Lancet 2010; 375: 1255–66
Lancet 2010; 375: 1255–66
4. Change in 24-hr ambulatory blood pressure
during the 8-week treatment period
• Blood-pressure lowering effects with LCZ696
• Remained consistent throughout the entire 24-hour dosing
period.
Sustained 24-hour Effect:
• Comparison of 24-Hour Mean Ambulatory Diastolic Blood
Pressure (duration 8 weeks)
• Minimal Differences and non- significant: LCZ696 vs.
Valsartan Doses
Ambulatory Diastolic Blood Pressure:
• Significantly lower 24-hour mean ambulatory systolic blood
pressure with 200 mg LCZ696 vs. 160 mg valsartan: -3.23
(95% CI -5.70 to -0.75).
Ambulatory Systolic Blood Pressure:
Lancet 2010; 375: 1255–66
Study Completion:
1215 patients successfully completed the 8-week treatment period.
Lancet 2010; 375: 1255–66
5. Change in placebo-subtracted sitting pulse pressure
during the 8-week treatment period:
Significant decreases in sitting pulse pressure
• Observed with 200 mg LCZ696 compared to 160 mg
valsartan (–2.25, 95% CI –4.45 to –0.06).
Significant decreases in sitting pulse
pressure
• A reduction of –3.32 (–5.51 to –1.13) in sitting pulse
pressure
A more pronounced effect seen with 400
mg LCZ696 compared to 320 mg valsartan,
with
Lancet 2010; 375: 1255–66
Change in placebo-subtracted sitting (A) pulse pressure
during the 8-week treatment period
Study Completion:
1215 patients successfully completed the 8-week treatment period.c
Lancet 2010; 375: 1255–66
6. Decreases in ambulatory pulse pressure
• Significantly different for 200 mg LCZ696 vs. 160 mg
valsartan (–2.48, –4.80 to –0.17).
Similarly, decreases in ambulatory pulse
pressure were
• A reduction of–3.95 (–6.28 to –1.62) in ambulatory pulse
pressure.
A more pronounced effect seen with 400
mg LCZ696 compared to 320 mg valsartan,
with
Study Completion:
1215 patients successfully completed the 8-week treatment period.
Lancet 2010; 375: 1255–66
Lancet 2010; 375: 1255–66
7. Blood pressure changes vs. placebo over 8-week treatment
Mean sitting systolic and diastolic blood pressure
• Complementary and fully additive reduction of blood
pressure
• Suggests that the drug holds promise for treatment of
hypertension and cardiovascular disease.
Compared with valsartan, dual-acting LCZ696 provides
LCZ696 demonstrated significantly greater reduction in
mean sitting diastolic blood pressure compared to
valsartan.
Average reduction with LCZ696: -2.17 mm Hg (95% CI -
3.28 to -1.06, p<0.0001).
Lancet 2010; 375: 1255–66
Change in placebo-subtracted mean sitting systolic blood pressure during the 8-week treatment
period
Change in placebo-subtracted mean sitting diastolic blood pressure during the 8-week treatment
period
Lancet 2010; 375: 1255–66
8. Blood-pressure reduction study using LCZ696(ARNi), a
novel dual-acting inhibitor:
Safety and Tolerance
Safety and Tolerance:
•LCZ696 was well tolerated.
•No cases of angio-edema reported.
•Only three serious adverse events during the treatment period, with none related to the study drug.
•No patient deaths occurred.
Lancet 2010; 375: 1255–66
Lancet 2010; 375: 1255–66
9. Study 4: PARAMETER STUDY
PARAMETER study
(Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With
Angiotensin Receptor Blocker Measuring Arterial Stiffness in the Elderly).
Hypertension. 2017;69:411-420.
Hypertension. 2017;69:411-420.
10. PARAMETER STUDY
Central aortic systolic pressure (CASP) and pulse pressure from
baseline at wk 12 and 52 wk in elderly
• Sacubitril/valsartan reduced central aortic systolic
pressure greater than olmesartan by -3.7 mmHg
(P=0.010).
Primary Assessment at week 12:
• Central aortic pulse pressure: -2.4 mmHg
(P<0.012).
Secondary Assessments at Week 12:
Hypertension. 2017;69:411-420.
Hypertension. 2017;69:411-420.
11. PARAMETER STUDY
Peripheral and central 24-h mean ambulatory systolic blood
pressure (SBP) compare to olemesartan in elderly
• Mean 24-hour ambulatory brachial systolic blood
pressure: -4.1 mmHg (P<0.001).
• Mean 24-hour ambulatory central aortic systolic
pressure: -3.6 mmHg (P<0.001).
Secondary Assessments at Week 12:
• More patients needed add-on antihypertensive
therapy with olmesartan (47%) vs. sacubitril/valsartan
(32%; P<0.002).
Long-Term Results: After 52 weeks
Peripheral and central 24-h mean ambulatory systolic blood
pressure (SBP): at wk 12 (A) and wk 52 (B) end points
Hypertension. 2017;69:411-420.
12. Efficacy and Safety of Sacubitril/Valsartan vs.
Olmesartan in essential hypertension
• Male or female Japanese patients ≥20 years old.
• Included both treated and untreated mild to moderate systolic hypertension.
• Approximately 30% of the study population comprised elderly patients (≥65 years).
Study Population Eligibility:
Hypertension Research (2022) 45:824–833
Hypertension Research (2022) 45:824–833
13. Efficacy of ARNi versus olmesartan in Japanese patients with
essential hypertension:
Change in mean sitting SBP, DBP and PP
• Sacubitril/Valsartan vs. Olmesartan (Week
8):
Superior BP Reductions -
• Superior mean systolic blood pressure
(msSBP) reduction over olmesartan.
• Between-treatment difference: -5.01 mmHg
(P < 0.001 for non-inferiority and superiority)
(Fig. 2).
Sacubitril/valsartan 200 mg:
• Greater msSBP reductions from baseline
compared to olmesartan at Week 8.
• Between-treatment difference: -6.97 mmHg
(P < 0.001) (Fig. 2).
Sacubitril/valsartan 400 mg:
Change from baseline in msSBP, msDBP, and msPP at Week 8
Hypertension Research (2022) 45:824–833
Hypertension Research (2022) 45:824–833
14. Efficacy of ARNi versus olmesartan in Japanese patients with
essential hypertension:
Proportion of patients who achieved control BP
Proportion of patients who achieved overall BP, systolic and diastolic blood
pressure control and response at the Week 8 endpoint
• More patients achieved BP control with
Sacubitril/Valsartan doses.
• Higher percentages of patients achieved systolic BP
response (msSBP < 140 mmHg or ≥20 mmHg
reduction) with Sacubitril/Valsartan compared to
olmesartan.
• Similarly, Sacubitril/Valsartan treatment showed
greater diastolic BP response (msDBP < 90 mmHg or
≥10 mmHg reduction) than olmesartan.
Sacubitril/Valsartan vs. Olmesartan
Hypertension Research (2022) 45:824–833
Hypertension Research (2022) 45:824–833
16. Sacubitril–valsartan for apparent resistant hypertension in
heart failure with preserved ejection fraction.
• Examined systolic blood pressure changes in different hypertension categories.
Study Focus:
• Week -2: End of valsartan 80 mg twice daily open run-in.
• Week 0: End of sacubitril–valsartan 49/51 mg open run-in.
• Followed by double-blind treatment: valsartan 160 mg twice daily or sacubitril–valsartan 97/103
Treatment Phases:
Jackson AM et al. European Heart Journal (2021) 42, 3741–3752
17. Sacubitril–valsartan for apparent resistant hypertension in
heart failure with preserved ejection fraction:
Significant reduction in systolic blood pressure
• Controlled blood pressure
• 'Non-resistant' hypertension
• 'Apparent resistant' hypertension
• 'Apparent mineralocorticoid receptor
antagonist-resistant' hypertension
Hypertension Categories
Analyzed:
Jackson AM et al. European Heart Journal (2021) 42, 3741–3752
• Almost one in six patients with heart failure and
preserved ejection fraction had apparent
resistant hypertension in PARAGON-HF and this
was associated with worse clinical outcomes;
• Neprilysin inhibition reduced systolic blood
pressure significantly in these patients
Jackson AM et al. European Heart Journal (2021) 42, 3741–3752
18. Sacubitril–valsartan for apparent resistant hypertension in heart
failure with preserved ejection fraction:
Efficacy of ARNi vs Valsartan: Changes in systolic blood pressure
• Sacubitril–Valsartan vs. Valsartan
• More apparent resistant hypertension patients
achieved controlled systolic BP by Week 16 with
sacubitril–valsartan (47.9%) compared to
valsartan (34.3%).
• OR: 1.78 (95% CI 1.30–2.43).
Controlled Systolic BP Achievement
• Sacubitril–Valsartan vs. Valsartan
• Stronger response observed in apparent MRA-
resistant hypertension patients with sacubitril–
valsartan (43.6%) compared to valsartan
(28.4%).
• OR: 2.63 (95% CI 1.18–5.89).
Enhanced Response in MRA-Resistant
Hypertension Patients
Jackson AM et al. European Heart Journal (2021) 42, 3741–3752
Jackson AM et al. European Heart Journal (2021) 42, 3741–3752
19. Sacubitril–valsartan for apparent resistant hypertension in heart
failure with preserved ejection fraction:
Safety of ARNi vs Valsartan
Jackson AM et al. European Heart Journal (2021) 42, 3741–3752
• Similar trends in alternative apparent resistant hypertension definition.
• Remains true for apparent mineralocorticoid receptor antagonist-resistant hypertension.
Consistent Adverse Events:
• More with sacubitril–valsartan than
valsartan.
• Slight increase in apparent resistant
hypertension.
Hypotension:
• Less elevated in sacubitril–valsartan for
apparent resistant hypertension.
Serum Creatinine &
Potassium:
Jackson AM et al. European Heart Journal (2021) 42, 3741–3752
21. Study 10: 24-Hour BP Reduction of Sacubitril/Valsartan vs.
Olmesartan in Japanese Essential Hypertension Patients based
on Nocturnal BP Dipping.
• Recognizing the significance of nighttime BP and its abnormal nocturnal dipping pattern in
contributing to cardiovascular risk.
• Sacubitril/valsartan treatment addresses various mechanisms that have the potential to enhance
cardiovascular outcomes in hypertensive patients, given its influence on these factors.
Clinical Implications:
Kazuomi Kario et al. J Am Heart Assoc. 2023;12:e027612
22. 24-Hour BP Reduction of Sacubitril/Valsartan vs. Olmesartan:
Overall Change in Ambulatory BP
Data are least-squares mean change±standard error (repeated measures ANCOVA model).
Daytime: 6 am to 10 pm; nighttime: 10 pm to 6 am. ABP indicates ambulatory blood pressure; DBP,
diastolic blood pressure; and SBP, systolic blood pressure. *P
Change in ambulatory systolic blood pressure (A) and diastolic blood
pressure (B) from baseline to week 8
• More pronounced with both sacubitril/valsartan
dosages compared to olmesartan at week 8.
• Graphical representation in Figure 1.
Ambulatory BP Changes (24-hour,
Daytime, Nighttime):
• Sacubitril/valsartan 200 mg/d: 83%
• Sacubitril/valsartan 400 mg/d: 85%
• Olmesartan group: 58%
Proportion of Patients with ≥5 mm
Hg BP Reduction:
Kazuomi Kario et al. J Am Heart Assoc. 2023;12:e027612
Kazuomi Kario et al. J Am Heart Assoc. 2023;12:e027612
23. 24-Hour BP Reduction of Sacubitril/Valsartan vs. Olmesartan:
Change in ambulatory systolic blood pressure
Change in ambulatory systolic blood pressure (A and B) from baseline
to week 8
• Significant reductions from baseline to week 8 with
sacubitril/valsartan (200mg/d, 400mg/d) and olmesartan
(20mg/d) in both dipper and nondipper groups.
BP Reductions - All Groups (24-hour, Daytime,
Nighttime):
• Greatest reductions in the non-dipper groups.
• Sacubitril/valsartan achieved notably higher nighttime
SBP and DBP reduction compared to olmesartan
Nondipper Group Impact:
Kazuomi Kario et al. J Am Heart Assoc. 2023;12:e027612
Kazuomi Kario et al. J Am Heart Assoc. 2023;12:e027612
24. 24-Hour BP Reduction of Sacubitril/Valsartan vs. Olmesartan:
Change in ambulatory diastolic blood pressure
• Sacubitril/valsartan 200mg/d and 400mg/d: Greater
reduction in nighttime SBP (P=0.022, P<0.001) and
nighttime DBP (P=0.041, P<0.001) in nondippers
compared to dippers (Figure S2).
Nondipper vs. Dipper Comparisons (Nighttime):
• Sacubitril/valsartan 400mg/d achieved a larger reduction
in 24-hour SBP in nondippers (-16.4mmHg) than dippers
(-12.7mmHg).
• Between-group difference: -3.7mmHg (P=0.004)
Dose Comparison - Nondippers:
Change in ambulatory diastolic blood pressure (C and D) from baseline to week 8 in
patient subgroups based on nocturnal blood pressure dipping status
Kazuomi Kario et al. J Am Heart Assoc. 2023;12:e027612
Kazuomi Kario et al. J Am Heart Assoc. 2023;12:e027612
25. Study 10: 24-Hour BP Reduction of Sacubitril/Valsartan vs.
Olmesartan:
Overall 24-hour systolic ambulatory blood pressure of nocturnal blood pressure
Time course of changes in 24-hour systolic ambulatory blood pressure overall
• Significantly more effective than olmesartan in
lowering 24-hour ambulatory systolic blood
pressure (SBP).
• Exception: No significant difference in patients
with diabetes
Sacubitril/Valsartan Effectiveness
and Patient Subgroups:
Kazuomi Kario et al. J Am Heart Assoc. 2023;12:e027612
26. 24-Hour BP Reduction of Sacubitril/Valsartan vs. Olmesartan:
Dipper and Non dipper ambulatory blood pressureof nocturnal blood pressure
Time course of changes in patients with a dipper (B) or nondipper (C)
profile of nocturnal blood pressure
• With sacubitril/valsartan 200mg/d:
• Greater ambulatory BP reduction in women compared to men.
• Greater reduction in patients with body mass index ≥25kg/m² than
<25kg/m² (Figure S3).
Gender and Body Mass Index Impact on
Effectiveness:
• With sacubitril/valsartan 400mg/d:
• Greater ambulatory BP reduction in patients with nondipper vs. dipper
profile.
• Greater reduction in patients with baseline estimated glomerular
filtration rate <60 vs. ≥60mL/min per 1.73m².
• Greater reduction in men vs. women.
• Greater reduction in patients with body mass index <25kg/m² vs.
≥25kg/m² (Figure S3).
Dosage and Patient Characteristics:
Kazuomi Kario et al. J Am Heart Assoc. 2023;12:e027612
Kazuomi Kario et al. J Am Heart Assoc. 2023;12:e027612
27. Response to Therapy
• Over 30% of sacubitril/valsartan patients achieved BP control
(24-hour SBP <130mmHg, 24-hour DBP <80mmHg) by week 8
on average.
• Nondipper subgroup: Higher BP control rates at week 8 with both
sacubitril/valsartan doses compared to olmesartan.
• Dipper subgroup: Differences less prominent (Figure 4).
Response Rates and BP Control:
• No variation in the proportion of patients experiencing a change
in nocturnal BP dipping status among treatment groups
throughout the study.
Nocturnal BP Dipping Status Change:
24-Hour BP Reduction of Sacubitril/Valsartan vs. Olmesartan:
Blood pressure control rate at week 8 in patients with a dipper or nondipper profile of
nocturnal blood pressure.
Kazuomi Kario et al. J Am Heart Assoc. 2023;12:e027612
Kazuomi Kario et al. J Am Heart Assoc. 2023;12:e027612
29. Sac/ Val versus Valsartan in regressing myocardial
fibrosis in hypertension
Front. Cardiovasc. Med. (Aug 2023)10:1248468. Once Daily
ARNI in
Hypertension
Sac/Val: Initial Dose 100-200mg OD, Max 400mg OD
Valsartan: Initial dose 80-160mg OD, Max 320 mg OD
Duration of Study:52 weeks
Group
1:1
Rando
mizatio
n
Singapore: 5 Centers: National Heart
Research Institute Singapore (NHRIS)
Primary endpoint:
• Change in CMR-derived diffuse
interstitial fibrosis volume
Secondary endpoint:
• CMR derived:
• LVM
• LVV
• BP Parameter:
• Office BP
• 24hr ambulatory BP
Health-related quality of life
assessment
• EuroQol EQ-5D-3L
questionnaire
Safety parameters:
• Serum potassium level
• Adverse Drug Reaction
Conclusion:
• REVERSE-LVH is the first trial that examines the anti-fibrotic potential of sacubitril/valsartan in a clinical population, guided by imaging.
• Myocardial fibrosis, a hallmark of HF, has shown regression on histology with lisinopril and losartan in HHD, torasemide in hypertensive
HF, and spironolactone in non-hypertensive HF
31. NT-Pro BNP Trajectory with ARNI in PARAGON HF
J Am Coll Cardiol HF. 2020;8 (5) 372–381
32. Treatment Effect Across Left Ventricular Ejection Fraction:
PARADIGM HF and PARAGON HF
Solomon et al. Circulation. 2020;141:352–361
Ejection Fraction (%)
33.
34. ARNI-PRESERVED study: Safety & Effectiveness of
ARNI in Indian Patients with HFpEF (Ref.: Heart India 2021;9:179-83)
Comparison of vital parameters, laboratory results,
and ECHO parameters at the initial visit & 6-months
follow-up
• 154 HF patients with EF ≥ 50%,
• NYHA class II, III symptoms,
• NT-pro-BNP ≥600 pg/mL
• Yashoda Hospitals, Hyderabad,
Telangana
35. Eligibility for sacubitril/valsartan in HFmr/r EF (EF < 50%)
based on PARADIGM-HF/PARAGON-HF selection
criteria
Overall eligibility was 64%
in females vs. 62% in males
Journal of Internal Medicine, 2021, 289; 369–384
37. Hypertension present in >50% of HF patients:
Heart failure registries
Clinical Hypertension (2020) 26:1
38. Sacubitril–valsartan as a treatment for apparent
resistant hypertension in patients with HFpEF
European Heart Journal (2021) 42, 3741–3752
39. Effect of sacubitril/valsartan compared to olmesartan on
cardiovascular remodelling in subjects with essential hypertension
European Heart Journal (2017) 38, 3308–3317
Changes in least squares mean left ventricle
mass from baseline
Changes in least squares mean left ventricle
mass index from baseline.
—Effective treatment of systolic hypertension in elderly patients remains a major therapeutic challenge. A multicenter, double-blind, randomized controlled trial with sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, was conducted to determine its effects versus olmesartan (angiotensin receptor blocker) on central aortic pressures, in elderly patients (aged ≥60 years) with systolic hypertension and pulse pressure >60 mmHg, indicative of arterial stiffness. Patients (n=454; mean age, 67.7 years; mean seated systolic blood pressure, 158.6 mmHg; mean seated pulse pressure, 69.7 mmHg) were randomized to receive once-daily sacubitril/valsartan 200 mg or olmesartan 20 mg, force titrated to double the initial doses after 4 weeks, before primary assessment at 12 weeks. The study extended double-blind treatment for 12 to 52 weeks, during which amlodipine (2.5–5 mg) and subsequently hydrochlorothiazide (6.25–25 mg) were added-on for patients not achieving blood pressure target (
Study Objective:
Investigate the efficacy of sacubitril/valsartan vs. olmesartan in treating systolic hypertension in elderly patients.
Study Design:
Multicenter, double-blind, randomized controlled trial.
Elderly patients (aged ≥60 years) with systolic hypertension and pulse pressure >60 mmHg.
Patient Characteristics:
454 patients, mean age 67.7 years, mean seated systolic blood pressure 158.6 mmHg, mean seated pulse pressure 69.7 mmHg.
Treatment Regimens:
Randomized to receive once-daily sacubitril/valsartan 200 mg or olmesartan 20 mg.
Force titrated to double initial doses after 4 weeks.
Primary Assessment:
At week 12, sacubitril/valsartan reduced central aortic systolic pressure greater than olmesartan by -3.7 mmHg (P=0.010).
Secondary Assessments at Week 12:
Central aortic pulse pressure: -2.4 mmHg (P<0.012).
Mean 24-hour ambulatory brachial systolic blood pressure: -4.1 mmHg (P<0.001).
Mean 24-hour ambulatory central aortic systolic pressure: -3.6 mmHg (P<0.001).
Sleep Effect:
Pronounced differences in 24-hour ambulatory pressures observed during sleep.
Long-Term Results:
After 52 weeks, blood pressure parameters similar between treatments (P<0.002).
More patients needed add-on antihypertensive therapy with olmesartan (47%) vs. sacubitril/valsartan (32%; P<0.002).
Tolerability and Safety:
Both treatments equally well tolerated.
Study Name:
PARAMETER study (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Measuring Arterial Stiffness in the Elderly).
Significant Findings:
Demonstrated the superiority of sacubitril/valsartan over olmesartan in reducing central aortic and brachial pressures in elderly patients with systolic hypertension and arterial stiffness.
Study Objective:
Investigate the efficacy of sacubitril/valsartan vs. olmesartan in treating systolic hypertension in elderly patients.
Study Design:
Multicenter, double-blind, randomized controlled trial.
Elderly patients (aged ≥60 years) with systolic hypertension and pulse pressure >60 mmHg.
Patient Characteristics:
454 patients, mean age 67.7 years, mean seated systolic blood pressure 158.6 mmHg, mean seated pulse pressure 69.7 mmHg.
Treatment Regimens:
Randomized to receive once-daily sacubitril/valsartan 200 mg or olmesartan 20 mg.
Force titrated to double initial doses after 4 weeks.
Primary Assessment:
At week 12, sacubitril/valsartan reduced central aortic systolic pressure greater than olmesartan by -3.7 mmHg (P=0.010).
Secondary Assessments at Week 12:
Central aortic pulse pressure: -2.4 mmHg (P<0.012).
Mean 24-hour ambulatory brachial systolic blood pressure: -4.1 mmHg (P<0.001).
Mean 24-hour ambulatory central aortic systolic pressure: -3.6 mmHg (P<0.001).
Sleep Effect:
Pronounced differences in 24-hour ambulatory pressures observed during sleep.
Long-Term Results:
After 52 weeks, blood pressure parameters similar between treatments (P<0.002).
More patients needed add-on antihypertensive therapy with olmesartan (47%) vs. sacubitril/valsartan (32%; P<0.002).
Tolerability and Safety:
Both treatments equally well tolerated.
Study Name:
PARAMETER study (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Measuring Arterial Stiffness in the Elderly).
Significant Findings:
Demonstrated the superiority of sacubitril/valsartan over olmesartan in reducing central aortic and brachial pressures in elderly patients with systolic hypertension and arterial stiffness.
Study Overview: Efficacy and Safety of Sacubitril/Valsartan vs. Olmesartan
Phase III study evaluating sacubitril/valsartan's efficacy and safety in Japanese patients with essential hypertension.
Patients (n = 1161) aged ≥20 years with mild to moderate hypertension (mean sitting systolic blood pressure [msSBP] ≥150 to <180 mmHg).
Randomized into three groups:
Sacubitril/valsartan 200 mg (n = 387)
Sacubitril/valsartan 400 mg (n = 385)
Olmesartan 20 mg (n = 389)
Treatment duration: Once daily for 8 weeks.
Primary and Secondary Assessments:
Primary assessment: Reduction in msSBP from baseline with sacubitril/valsartan 200 mg vs. olmesartan 20 mg at Week 8.
Sacubitril/valsartan 200 mg achieved significantly greater msSBP reduction vs. olmesartan at Week 8:
Between-treatment difference: -5.01 mmHg (95% CI: -6.95 to -3.06 mmHg, P < 0.001 for noninferiority and superiority).
Secondary assessments:
Greater msSBP reduction with sacubitril/valsartan 400 mg vs. olmesartan at Week 8.
Reductions in msDBP and msPP with both sacubitril/valsartan doses vs. olmesartan (P < 0.05 for all).
Higher overall blood pressure (BP) control rate with sacubitril/valsartan treatment.
Safety and Tolerability:
Sacubitril/valsartan safety and tolerability profiles generally comparable to olmesartan.
Adverse event rate with sacubitril/valsartan not dose-dependent.
Conclusion:
Sacubitril/valsartan more effective in achieving superior BP reduction and higher proportion of patients reaching target BP goals compared to olmesartan.
Effective and well-tolerated treatment option for Japanese patients with mild to moderate essential hypertension.
Week 8: More patients achieved overall BP control with both sacubitril/valsartan doses than olmesartan (Fig. 3).
Higher percentage of patients in sacubitril/valsartan groups achieved SBP response (msSBP < 140 mmHg or ≥20 mmHg reduction) compared to olmesartan.
Similarly, greater percentage of patients in sacubitril/valsartan groups achieved DBP response (msDBP < 90 mmHg or ≥10 mmHg reduction) compared to olmesartan.
Aims Patients with heart failure and preserved ejection fraction (HFpEF) frequently have difficult-to-control hypertension. We examined the effect of neprilysin inhibition on ‘apparent resistant hypertension’ in patients with HFpEF in the PARAGON-HF trial, which compared the effect of sacubitril–valsartan with valsartan. ................................................................................................................................................................................................... Methods and results In this post hoc analysis, patients were categorized according to systolic blood pressure at the end of the valsartan run-in (n = 4795). ‘Apparent resistant hypertension’ was defined as systolic blood pressure >_140 mmHg (>_135 mmHg if diabetes) despite treatment with valsartan, a calcium channel blocker, and a diuretic. ‘Apparent mineralocorticoid receptor antagonist (MRA)-resistant’ hypertension was defined as systolic blood pressure >_140 mmHg (>_135 mmHg if diabetes) despite the above treatments and an MRA. The primary outcome in the PARAGON-HF trial was a composite of total hospitalizations for heart failure and death from cardiovascular causes. We examined clinical endpoints and the safety of sacubitril–valsartan according to the hypertension category. We also examined reductions in blood pressure from the end of valsartan run-in to Weeks 4 and 16 after randomization. Overall, 731 patients (15.2%) had apparent resistant hypertension and 135 (2.8%) had apparent MRA-resistant hypertension. The rate of the primary outcome was higher in patients with apparent resistant hypertension [17.3; 95% confidence interval (CI) 15.6–19.1 per 100 person-years] compared to those with a controlled systolic blood pressure (13.4; 12.7–14.3 per 100 person-years), with an adjusted rate ratio of 1.28 (95% CI 1.05–1.57). The reduction in systolic blood pressure at Weeks 4 and 16, respectively, was greater with sacubitril–valsartan vs. valsartan in patients with apparent resistant hypertension [-4.8 (-7.0 to -2.5) and 3.9 (-6.6 to -1.3) mmHg] and apparent MRA-resistant hypertension [-8.8 (-14.0 to -3.5) and -6.3 (-12.5 to -0.1) mmHg]. The proportion of patients with apparent resistant hypertension achieving a controlled systolic blood pressure by Week 16 was 47.9% in the sacubitril–valsartan group and 34.3% in the valsartan group [adjusted odds ratio (OR) 1.78, 95% CI 1.30–2.43]. In patients with apparent MRA-resistant hypertension, the respective proportions were 43.6% vs. 28.4% (adjusted OR 2.63, 95% CI 1.18–5.89). ................................................................................................................................................................................................... Conclusion Sacubitril–valsartan may be useful in treating apparent resistant hypertension in patients with HFpEF, even in those who continue to have an elevated blood pressure despite treatment with at least four antihypertensive drug classes, including an MRA
Aims:
Investigate the effect of neprilysin inhibition on "apparent resistant hypertension" in patients with heart failure and preserved ejection fraction (HFpEF) using data from the PARAGON-HF trial.
Compare the effects of sacubitril–valsartan with valsartan in this context.
Methods and Results:
Categorized patients (n = 4795) based on systolic blood pressure after valsartan run-in.
Defined "apparent resistant hypertension" as systolic BP >140 mmHg (>135 mmHg if diabetes) despite valsartan, calcium channel blocker, and diuretic treatment.
Defined "apparent MRA-resistant hypertension" as systolic BP >140 mmHg (>135 mmHg if diabetes) despite above treatments and a mineralocorticoid receptor antagonist (MRA).
Primary outcome: Composite of heart failure hospitalizations and cardiovascular death.
Explored clinical endpoints, safety of sacubitril–valsartan, and BP reductions according to hypertension category.
15.2% (731 patients) had apparent resistant hypertension; 2.8% (135 patients) had apparent MRA-resistant hypertension.
Primary outcome rate higher in apparent resistant hypertension patients (17.3) vs. controlled BP patients (13.4) per 100 person-years, adjusted rate ratio of 1.28.
Systolic BP reductions with sacubitril–valsartan vs. valsartan:
Apparent resistant hypertension: -4.8 mmHg (Week 4), 3.9 mmHg (Week 16)
Apparent MRA-resistant hypertension: -8.8 mmHg (Week 4), -6.3 mmHg (Week 16)
Proportion achieving controlled systolic BP by Week 16:
Apparent resistant hypertension: 47.9% (sacubitril–valsartan), 34.3% (valsartan), adjusted odds ratio 1.78.
Apparent MRA-resistant hypertension: 43.6% (sacubitril–valsartan), 28.4% (valsartan), adjusted odds ratio 2.63.
Conclusion:
Sacubitril–valsartan may be effective in treating apparent resistant hypertension in HFpEF patients.
Beneficial even for those with persistently elevated BP despite four antihypertensive drug classes, including an MRA.
Aims:
Study the impact of neprilysin inhibition on "apparent resistant hypertension" in HFpEF patients using PARAGON-HF trial data.
Compare sacubitril–valsartan with valsartan.
Methods and Results:
Categorized patients (n = 4795) by systolic BP after valsartan run-in.
"Apparent resistant hypertension" defined as BP >140 mmHg (>135 mmHg if diabetes) despite treatment.
"Apparent MRA-resistant hypertension" defined similarly.
Primary outcome: Heart failure hospitalizations and cardiovascular death.
15.2% (731 patients) had apparent resistant hypertension; 2.8% (135 patients) had apparent MRA-resistant hypertension.
Higher primary outcome rate in apparent resistant hypertension (17.3) vs. controlled BP (13.4) per 100 person-years, adjusted rate ratio 1.28.
Systolic BP reductions with sacubitril–valsartan vs. valsartan:
Apparent resistant hypertension: -4.8 mmHg (Week 4), 3.9 mmHg (Week 16)
Apparent MRA-resistant hypertension: -8.8 mmHg (Week 4), -6.3 mmHg (Week 16)
Proportion achieving controlled systolic BP by Week 16:
Apparent resistant hypertension: 47.9% (sacubitril–valsartan), 34.3% (valsartan), adjusted odds ratio 1.78.
Apparent MRA-resistant hypertension: 43.6% (sacubitril–valsartan), 28.4% (valsartan), adjusted odds ratio 2.63.
Conclusion:
Sacubitril–valsartan effective for apparent resistant hypertension in HFpEF patients.
Useful for patients with persistently elevated BP despite multiple antihypertensive drugs, including an MRA.
BACKGROUND: Nighttime blood pressure (BP) and an abnormal nocturnal BP dipping profile are important cardiovascular risk factors in patients with hypertension. This post hoc analysis investigated the effects of sacubitril/valsartan on 24-hour BP in patients with mild-to-moderate hypertension and in patient subgroups based on nocturnal BP dipping status. METHODS AND RESULTS: Data from a randomized clinical trial comparing the BP-lowering effects of 8weeks of treatment with sacubitril/valsartan (200 or 400mg/d) and olmesartan (20mg/d) in Japanese patients with mild-to-moderate hypertension were analyzed. The primary end point was change in 24-hour, daytime, and nighttime BP in patient subgroups based on nocturnal BP dipping status (dipper, nondipper). Six hundred thirty-two patients with baseline and follow-up ambulatory BP data were included. Both sacubitril/valsartan dosages reduced 24-hour, daytime, and nighttime systolic BP, and 24-hour and daytime diastolic BP, to a significantly greater extent than olmesartan in the dipper and nondipper groups. However, between-group differences in nighttime systolic BP were more significant in the nondipper group (difference [95% CI] for sacubitril/valsartan 200 and 400mg/d versus olmesartan 20mg/d: –4.6 [95% CI, −7.3 to −1.8] and −6.8 [95% CI, −9.5 to −4.1] mmHg, respectively; P
Background:
Nocturnal blood pressure (BP) and abnormal dipping profile are cardiovascular risks in hypertension.
Study investigates sacubitril/valsartan effects on 24-hour BP in mild-to-moderate hypertension.
Focus on patient subgroups by nocturnal BP dipping status.
Methods and Results:
Randomized trial analyzed BP effects of sacubitril/valsartan (200/400mg/d) and olmesartan (20mg/d).
Japanese patients with mild-to-moderate hypertension over 8 weeks.
Primary goal: Change in 24-hour, daytime, nighttime BP in dipper/nondipper subgroups.
632 patients' baseline/follow-up BP data studied.
Both sacubitril/valsartan doses lowered BP more than olmesartan in dipper/nondipper groups.
Significant reduction in 24-hour, daytime, nighttime systolic BP.
Also lowered 24-hour, daytime diastolic BP.
Nighttime systolic BP reduction more significant in nondipper group:
Sacubitril/valsartan 200mg/d: -4.6 mmHg
Sacubitril/valsartan 400mg/d: -6.8 mmHg
Between-group differences: P<0.01 and P<0.001.
Greatest between-group differences in BP control rate in nondipper subgroup:
Sacubitril/valsartan 200mg/d: 34.4%
Sacubitril/valsartan 400mg/d: 42.6%
Olmesartan 20mg/d: 23.1%
Conclusions:
Sacubitril/valsartan valuable for nondipper profile patients' nocturnal BP.
Confirms potent 24-hour BP lowering in Japanese hypertension patients.
Highlights therapeutic potential of sacubitril/valsartan in hypertensive populations.
Sacubitril/Valsartan Effectiveness and Patient Subgroups:
Significantly more effective than olmesartan in lowering 24-hour ambulatory systolic blood pressure (SBP).
Exception: No significant difference in patients with diabetes (Figure S3).
Gender and Body Mass Index Impact on Effectiveness:
With sacubitril/valsartan 200mg/d:
Greater ambulatory BP reduction in women compared to men.
Greater reduction in patients with body mass index ≥25kg/m² than <25kg/m² (Figure S3).
Dosage and Patient Characteristics:
With sacubitril/valsartan 400mg/d:
Greater ambulatory BP reduction in patients with nondipper vs. dipper profile.
Greater reduction in patients with baseline estimated glomerular filtration rate <60 vs. ≥60mL/min per 1.73m².
Greater reduction in men vs. women.
Greater reduction in patients with body mass index <25kg/m² vs. ≥25kg/m² (Figure S3).
Response Rates and BP Control:
Over 30% of patients on sacubitril/valsartan achieved BP control (24-hour SBP <130mmHg, 24-hour DBP <80mmHg) by week 8 on average.
BP control rates at week 8 higher with both sacubitril/valsartan doses than with olmesartan in the nondipper subgroup.
Differences between sacubitril/valsartan and olmesartan less pronounced in the dipper subgroup (Figure 4).
Nocturnal BP Dipping Status Change:
No difference in the proportion of patients with a change in nocturnal BP dipping status between treatment groups during the study.
Sacubitril/ Valsartan versus Valsartan in regressing myocardial fibrosis in hypertension