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Changing the treatment of heart failure with reduced ejection fraction: clinical use of sacubitril-valsartan combination.

Abstract Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk of morbidity and mortality. Sacubitril valsartan (previously known as LCZ696) is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the first in class angiotensin receptor neprilysin inhibitor (ARNI) since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides (NPs), bradykinin, endothelin and angiotensin II (Ang-II). Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-II (with opposite biological actions). So, a combined inhibition of these both systems (Sacubitril / valsartan) may enhance the benefits of NPs effects in HF (natriuresis, diuresis, etc) while Ang-II receptor is inhibited (reducing vasoconstriction and aldosterone release). In a large clinical trial (PARADIGM-HF with 8442 patients), this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF (compared to enalapril). This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction.
PMID
Related Publications

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Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial.

Sacubitril/valsartan in heart failure: latest evidence and place in therapy.

Authors

Mayor MeshTerms
Keywords

Heart failure

LCZ696

Neprilysin

PARADIGM-HF

Sacubitril

Valsartan

Journal Title journal of geriatric cardiology : jgc
Publication Year Start




PMID- 28133468
OWN - NLM
STAT- In-Data-Review
DA  - 20170130
LR  - 20170201
IS  - 1671-5411 (Print)
IS  - 1671-5411 (Linking)
VI  - 13
IP  - 11
DP  - 2016 Nov
TI  - Changing the treatment of heart failure with reduced ejection fraction: clinical 
      use of sacubitril-valsartan combination.
PG  - 914-923
LID - 10.11909/j.issn.1671-5411.2016.11.006 [doi]
AB  - Despite significant therapeutic advances, patients with chronic heart failure
      (HF) remain at high risk of morbidity and mortality. Sacubitril valsartan
      (previously known as LCZ696) is a new oral agent approved for the treatment of
      symptomatic chronic heart failure in adults with reduced ejection fraction. It is
      described as the first in class angiotensin receptor neprilysin inhibitor (ARNI) 
      since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin II
      receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down
      several vasoactive peptides including natriuretic peptides (NPs), bradykinin,
      endothelin and angiotensin II (Ang-II). Therefore, a natural consequence of its
      inhibition is an increase of plasmatic levels of both, NPs and Ang-II (with
      opposite biological actions). So, a combined inhibition of these both systems
      (Sacubitril / valsartan) may enhance the benefits of NPs effects in HF
      (natriuresis, diuresis, etc) while Ang-II receptor is inhibited (reducing
      vasoconstriction and aldosterone release). In a large clinical trial (PARADIGM-HF
      with 8442 patients), this new agent was found to significantly reduce
      cardiovascular and all cause mortality as well as hospitalizations due to HF
      (compared to enalapril). This manuscript reviews clinical evidence for sacubitril
      valsartan, dosing and cautions, future directions and its considered place in the
      therapy of HF with reduced ejection fraction.
FAU - Kaplinsky, Edgardo
AU  - Kaplinsky E
AD  - Cardiology Unit, Medicine Department, Hospital Municipal de Badalona.Via Augusta 
      Av. 9-13 (08911), Badalona, Spain.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - China
TA  - J Geriatr Cardiol
JT  - Journal of geriatric cardiology : JGC
JID - 101237881
PMC - PMC5253408
OTO - NOTNLM
OT  - Heart failure
OT  - LCZ696
OT  - Neprilysin
OT  - PARADIGM-HF
OT  - Sacubitril
OT  - Valsartan
EDAT- 2017/01/31 06:00
MHDA- 2017/01/31 06:00
CRDT- 2017/01/31 06:00
AID - 10.11909/j.issn.1671-5411.2016.11.006 [doi]
AID - jgc-13-11-914 [pii]
PST - ppublish
SO  - J Geriatr Cardiol. 2016 Nov;13(11):914-923. doi:
      10.11909/j.issn.1671-5411.2016.11.006.

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