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Overview, Indications, Clinical Evidence & Dosage
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Heart Failure - Overview
Heart failure is a progressive chronic syndrome characterized by decrease in functional
status and quality of life .
The burden of heart failure has increased to an estimated 23 million people, worldwide.
In India, the prevalence was estimated to be around 1.2/1000 people in the INDUS study.
As prevalence rates of heart failure are high and expected to rise in the near future
because of improved survival from acute cardiac events and the aging of the general
population, thus HF management has come to the front-stage of non-communicable
disease management programmes.
Once developed, heart failure has a 1-year mortality rate of 7.2% and a 1-year
hospitalization rate of 31.9% in patients with chronic heart failure, and in patients
hospitalized for acute heart failure, these rates increase to 17.4% and 43.9% .
The pathophysiology of heart failure involves a maladaptive response during which the
renin-angiotensin-aldosterone system (RAAS) is activated .
RAAS activation leads to vasoconstriction, hypertension, increased aldosterone levels,
increased sympathetic tone, and eventually, cardiac remodeling, all of which are
detrimental to the progression of the disease .
Indication
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Heart Failure
To reduce the risk of cardiovascular death and hospitalization for heart failure in
patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
Important update
Understanding ARNI in Hypertension
Understanding Heart Failure in India
Guidlines defined for the treatment of Heart Failure
Quick Review- Role of ARNI in Heart Failure final
Decoding the clinical Evidence for Sacubitril Valsartan in Heart Failure
The Drug Review Sacubitril Valsartan
John McMurray
BHF Cardiovascular Research Centre, University of Glasgow & Queen Elizabeth
University Hospital, Glasgow, Scotland, UK

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Dr. Partho P Chowdhury
MD (DELHI UNIVERSITY), DM (IPGMER,KOL) Consultant Interventional Cardiologist
Specialist in Radial Angioplasty, Complex Angioplasty, Pacemaker, ICD, CRT
Implantation, Device Closure
Meditrina Hospital, Jharkhand
Professor Dr. J.C Mohan
MBBS, MD (General Medicine) DM (Cardiology) M.NAMS FACC (Fellow American
College of Cardiology) FASE (Honorary Fellow of American Society of Echocardiography)
FESC (Fellow of European Society of Cardiology) Jaipur Golden Hospital, Delhi
Dr. Armendra Kumar Pandey
MBBS, DNB (Medicine) FNIC, DNB (Cardilogy)
Consultant-Cardiology Dharamshila Narayana Superspeciality Hospital
Watch Video At: https://youtu.be/sceEr6m2QnQ
Dr. Dilip Kumar

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MBBS, MD, DM (Card) FRCP (GLASG), FHRS, FSCAI, FESC, IBHRE, CCDS Chief
Academic Co-ordinator Medica Institute of Cardiac Sciences Kolkata
Watch Video At: https://youtu.be/5rOxlgEIXaY
Dr. Animesh Agarwal
MD, DM (Cardiology), AFESC International Associate American College of Cardiology
Senior Consultant & HOD Department of Cardiology Jindal Institute of Medical Sciences,
Haryana

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Watch Video At: https://youtu.be/7x2WKKUV1rA
Dr. Harpreet Singh Gilhotra
DM, FESC Director Cardiology
Sri Guru Harkrishan Sahib (C) Eye Hospital Trust, Sohan (Sohana Hospital)
Watch Video At: https://youtu.be/ovMzlsB4o3M

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Dr. Amit Handa
Consultant- Cardiologist
MD (Med.), DM (Cardiology) Ivy Multi Speciality Hospital Punjab
Watch Video At: https://youtu.be/YzWI1O20RCk
Dr. Niroj Kumar Mishra
M.D. (Medicine) Clinical Director
(AN ISO:9001:2008 CERTIFIED HOSPITAL) KAR CLINIC & HOSPITAL PVT.LTD.,
Bhubaneswar

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Watch Video At: https://youtu.be/0xvq7sAwrUA
Dr. Nitin Tiwari
M.B.B.S (Gold Medallist) D.M.(Card), D.N.B.(Card), M.D. (Card), D.N.B (Med.),
M.N.A.M.S., M.A.P.S.I.C., F.I.A.M.S.
FIC (France), FIC (Germany), FESC (Europe), FACC (USA) Interventional Cardiologist
WOCKHARDT HEART HOSPITAL, Nagpur

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Watch Video At: https://youtu.be/YbckiC1zSP8
Dr. Idris Ahmed Khan
MD, DM (Card, PGI Chandigarh)
Consultant Interventional Cardiologist BOMBAY HOSPITAL, INDORE
Watch Video At: https://youtu.be/vc9lm8gWjbg
Dr. Johann Christopher
MD, DNB (Cardiology)
Consultant Cardilogist Division of Cardiac Imaging CARE HOSPITALS, CARE
OUTPATIENT CENTRE Hyderabad

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Watch Video At: https://youtu.be/Kx0B93PygOw
Dr. C.K. Ponde
Consultant Cardiologist M.D. (Gen.Med), D.M (Card),
D.N.B. (Card) FACC (USA), FSCAI (USA) FCSI, FISE, FICC, FIAE
Watch Video At: https://youtu.be/vTx4E4Y3tZs

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Prof Dr Satyanarayan Routray
MBBS, MD (MEDICINE), DM (CARDIOLOGY), FICC,FCSI Professor and HOD
SCB Medical College & Hospital Cuttack
Watch Video At: https://youtu.be/lnBKczf--D0
Dr J.S Hiremath
DM (Cardiology), DNB (Cardiology) Fellow of American College of Cardiology Director:
Cath Lab, Ruby Hall Clinic
Chief Cardiologist, Hearty Transplant Department, Ruby Hall Clinic, Pune
About Azmarda
Azmarda contains Sacubitril/Valsartan, the first agent to be approved in a new class of
drugs called angiotensin receptor neprilysin inhibitor (ARNI) .
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How Azmarda Works?

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Sacubitril acts as a neprilysin inhibitor by preventing the breakdown of natriuretic
peptides. This leads to a prolonged duration of the favorable effects of these peptides.
Valsartan is an angiotensin receptor blocker, and it works by blocking the renin-
angiotensin-aldosterone system .
Composition
Pharmacokinetics of Azmarda
Absorption
Following oral administration, Azmarda dissociates into sacubitril, which is further
metabolized to sacubitrilat, and valsartan, which reach peak plasma concentrations in
0.5 hours, 2 hours, and 1.5 hours, respectively.
The oral absolute bioavailability of sacubitril and valsartan is estimated to be ≥ 60% and
23%, respectively. Azmarda can be administered with or without food.
Distribution
Azmarda is highly bound to plasma proteins (94% - 97%). Based on the comparison of
plasma and CSF exposures, sacubitrilat does cross the blood brain barrier to a limited
extent (0.28%).
Azmarda has an apparent volume of distribution ranging from 75L to 103L.
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Biotransformation
Sacubitril is readily converted to sacubitrilat by esterases; sacubitrilat is not further
metabolized to a significant extent.
Valsartan is minimally metabolized, as only about 20% of the dose is recovered as
metabolites.
Elimination
Following oral administration, 52 to 68% of sacubitril (primarily as sacubitrilat) and
~13% of valsartan and its metabolites are excreted in urine; 37 to 48% of sacubitril
(primarily as sacubitrilat), and 86% of valsartan and its metabolites are excreted in feces.
Sacubitril, sacubitrilat, and valsartan are eliminated from plasma with a mean
elimination half-life (T1/2) of approximately 1.43 hours, 11.48 hours, and 9.90 hours,
respectively.
Clinical Evidences

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Dosage
The recommended starting dose of AZMARDA is 100 mg twice daily.
A starting dose of 50 mg twice daily is recommended for patients not currently
taking an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II
receptor blocker (ARB), and should be considered for patients previously taking low
doses of these agents.
The dose of AZMARDA should be doubled every 2-4 weeks to the target dose of 200
mg twice daily, as tolerated by the patient.
Questions and Answers
1. What is Azmarda (Sacubitril Valsartan)?
2. What is Azmarda (Sacubitril Valsartan) indicated for?
3. How does Azmarda (Sacubitril Valsartan) work?

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4. What are the dosage forms and strengths of Azmarda (Sacubitril Valsartan)?
5. What are the dosage and administration of Azmarda (Sacubitril Valsartan)?
6. What is the clinical pharmacodynamics of Azmarda (Sacubitril Valsartan)?
7. What are the clinical pharmacokinetics of Azmarda (Sacubitril Valsartan)?
8. What benefits of Azmarda (Sacubitril Valsartan) have been shown in studies?
9. What are the risks associated with Azmarda (Sacubitril Valsartan)? What are the
precautions to be taken while using Azmarda (Sacubitril Valsartan)?
10. What are the contraindications of Azmarda (Sacubitril Valsartan)?
11. What are the adverse reactions of Azmarda (Sacubitril Valsartan)?
12. What are the precautions to be taken for special populations groups while using
Azmarda?
13. What is the safety profile of Azmarda (Sacubitril Valsartan) in females of
childbearing potential, pregnancy, breastfeeding, and fertility?
14. What happens to the overdosage of Azmarda (Sacubitril Valsartan)?
15. What measures are being taken to ensure the safe and effective use of Azmarda
(Sacubitril Valsartan)?
References
1. Chaturvedi V, Parakh N, Seth S, et al. Heart failure in India: The INDUS (INDiaUkieri
Study) study. J PractCardiovascSci2016;2:28-35 2. Murphy SP, Ibrahim NE, Januzzi JL
Jr. Heart Failure With Reduced Ejection Fraction: A Review. JAMA. 2020 Aug
4;324(5):488-504 3. Nicolas D, Kerndt CC, Reed M. Sacubitril/Valsartan. [Updated 2021
Jul 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 4.
Ayalasomayajula, S., Langenickel, T., Pal, P., et.al (2017). Clinical Pharmacokinetics of
Sacubitril/Valsartan (LCZ696): A Novel Angiotensin Receptor-Neprilysin Inhibitor.
Clinical pharmacokinetics, 56(12), 1461–1478.
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