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There are currently many kinds of
drugs for heart failure . Among them ,
the new drug LCZ 696 is recommended
by United States (US) guidelines as a
first- line treatment for chronic heart
failure . LCZ 696 is better than
conventional drugs at reducing cardiac
death and hospitalization due to heart
failure . Now, researchers from
Kumamoto University in Japan have
revealed that LCZ 696 can prevent
cardiac rupture and heart failure
following acute myocardial infarction ,
which is one of the causes of chronic
heart failure .
Heart disease is the leading cause of
death in the world, and the majority of
those deaths are caused by heart failure
and acute myocardial infarction . In the
past , angiotensin converting enzyme
inhibitors (ACE inhibitors ) or
Angiotensin II Receptor Blockers (ARBs)
were used in combination with other
drugs as the initial therapy for heart
failure and acute myocardial infarction .
ACE inhibitors and ARBs both inhibit
the system responsible for regulating
blood pressure , the Renin - Angiotensin -
Aldosterone System (RAAS ), which
causes high blood pressure when it
becomes overactive .
LCZ 696 is a novel drug that combines
Valsartan, a traditional
antihypertensive drug, and Sacubitril ,
which has an organ- protective effect .
Sacubitril inhibits neprilysin which
decomposes hormones secreted mainly
from the heart called Atrial Natriuretic
Peptide (ANP ), and B - type Natriuretic
Peptide (BNP ). A 2014 large - scale
clinical trial of patients who had chronic
heart failure with reduced ejection
fraction (the percentage of blood exiting
the heart at each contraction ) reported
that the number of cardiac deaths and
re - hospitalizations due to heart failure
was reduced significantly with LCZ 696
treatment than with existing ACE
inhibitors . LCZ 696 is now widely used
in Europe and the United States as the
first treatment for chronic heart failure .
LCZ 696 was established as a chronic
heart failure treatment because it
suppresses RAAS action and enhances
the function of the natriuretic peptide
system , which protects the heart .
However , it is not yet clear whether it is
useful in the acute phase of acute
myocardial infarction , which causes
chronic heart failure . In a myocardial
infarction , the wall between the
necrotic and non- necrotic areas of the
heart is torn causing rupture and
bleeding at the boundary. Ten percent
of deaths from myocardial infarction is
attributed to cardiac rupture . Therefore ,
researchers examined the effect of
LCZ 696 , using an artificial myocardial
infarction mouse model (a wild- type
mouse) .
The day after the myocardial infarction
model mice were created , they were
divided into groups that (1 ) did not
receive any treatment (control group),
(2 ) received an ACE inhibitor, and (3 )
received LCZ 696 . The researchers found
that the mortality rate due to cardiac
rupture occurring within one week after
myocardial infarction was significantly
lower in the LCZ 696 treatment group
than in the other two groups . Gene
expression in the area of myocardial
infarction was analyzed to investigate
the mechanism that LCZ 696 could
inhibit cardiac rupture . The researchers
found that the expression of genes
involved in inflammation - related
cytokines (IL - 1 β , IL - 6 ) and in tissue
degrading MMP- 9 was clearly reduced
in the LCZ 696 treatment group. An
increase in the function of the MMP- 9
gene is known to be related to the cause
of cardiac rupture .
In addition , microscopic observations of
the pathological tissue of the heart
showed that the number of
inflammatory cells was unchanged in all
groups , but the activity of MMP- 9 was
clearly lowered in the LCZ 696 treatment
group.
Furthermore, in experiments using
cultured mouse macrophages,
researchers confirmed that the
inflammation action of cytokines and
MMP- 9 can be more suppressed using
LCZ 696 rather than using valsartan or
sacubitril by themselves .
“ LCZ 696 is a new therapeutic drug that
improves the prognosis of patients with
chronic heart failure ,” said Dr.
Masanobu Ishii of Kumamoto
University . “ We know that ischemic
heart disease , especially myocardial
infarction , is one of the causes of
chronic heart failure and our study
revealed that LCZ 696 has a cardio -
protective effect against myocardial
infarction .”
“ This improves a patient ’s prognosis by
suppressing cardiac rupture ,” added
Associate Professor Koichi Kaikita . “ In
the future , it is expected that LCZ 696
will be used not only to treat chronic
heart failure but also as therapy after
acute myocardial infarction . ” This
research result was presented at the Hot
Line of the European Cardiology Society
(ESC) Congress 2017 held in Barcelona,
Spain, on 26 - 30 August , 2017 , and
posted on - line in the “ JACC; Basic to
Translational Science ” on 28 August
2017.
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