Heart
attack
patients
gained
faster
control
of
LDL
cholesterol
starting
PCSK9
inhibitor
therapy
immediately
in
the
cath
lab,
the
AMUNDSEN
trial
showed,
while
a
clinical
benefit
could
not
be
proven.
High-risk
patients
with
acute
myocardial
infarction
(MI)
who
had
a
first
injection
of
evolocumab
(Repatha)
right
before
percutaneous
coronary
intervention
(PCI)
were
significantly
more
likely
to
achieve
cholesterol
targets
1
year
into
the
study,
reported
Gilles
Montalescot,
MD,
PhD,
of
Pitié-Salpêtrière
Hospital
in
Paris.
The
proportion
of
patients
reaching
LDL
cholesterol
<55
mg/dL
and
at
least
50%
reduction
from
baseline
to
12
months
came
out
to
82%
among
those
given
upfront
evolocumab
versus
40%
of
peers
randomized
to
standard
care
(adjusted
OR
5.54,
95%
CI
4.50-6.82).
Meanwhile,
the
evolocumab
and
control
groups
shared
similar
rates
of
all-cause
death
or
unplanned
cardiovascular
hospitalization
at
12
months
(14.6%
vs
15.4%,
adjusted
OR
0.94,
95%
CI
0.73-1.19)
in
this
study
of
over
2,100
participants,
Montalescot
reported
at
the
European
Society
of
Cardiology
Congress
in
Munich,
Germany.
The
study
was
simultaneously
published
in
JAMA.
This
would
suggest
no
clinically
meaningful
acute
pleiotropic
effects
of
PCSK9
inhibitors,
beyond
LDL
cholesterol-mediated
effects,
in
adjunct
to
standard
care,
the
AMUNDSEN
trialists
suggested.
“This
study,
to
the
authors’
knowledge,
is
the
first
adequately
sized
randomized
trial
evaluating
systematic
PCSK9
inhibition
in
patients
with
acute
MI
at
the
time
of
mechanical
reperfusion
in
the
catheterization
laboratory,
added
to
standard
care
with
high-intensity
lipid-lowering
therapy,
compared
with
a
control
standard
care
group
in
whom
lipid-lowering
therapy
can
be
adjusted
and
intensified
—
including
with
PCSK9
inhibition
during
follow-up
—
as
currently
recommended
by
guidelines,”
Montalescot’s
group
noted.
Lipid
lowering
is
of
great
interest
for
heart
attack
patients,
as
acute
coronary
syndrome
patients
with
elevated
LDL
cholesterol
are
at
high
risk
for
long-term
recurrent
cardiovascular
events.
Some
would
argue
that
PCSK9
inhibitors
—
powerful
lipid-lowering
agents
indicated
for
primary
and
secondary
prevention
of
cardiovascular
disease
—
are
well
positioned
for
a
larger
role
in
acute
MI.
One
trial
had
shown
another
PCSK9
inhibitor,
alirocumab
(Praluent),
to
boost
LDL
cholesterol
lowering
as
an
early
adjunct
to
standard
high-intensity
statins
in
acute
MI,
the
idea
being
that
lower
LDL
cholesterol
is
better
for
secondary
prevention.
AMUNDSEN
now
pumps
the
brakes
on
rapid
lipid-lowering
starting
in
the
cath
lab.
“This
is
a
study
that,
in
some
ways,
challenges
the
currently
popular
‘strike
early
and
strike
strong’
concept,
although
one
could
argue
that
starting
treatment
early
during
hospitalization
is
intended
to
improve
adherence,
rather
than
to
achieve
true
pleiotropic
effects
or
improve
cardiovascular
outcomes
compared
with
a
more
delayed
initiation,”
commented
Davide
Capodanno,
MD,
PhD,
of
University
of
Catania,
in
Catania,
Italy.
Capodanno
highlighted
the
very
low
3.8%
of
standard-care
patients
in
the
trial
who
subsequently
received
a
PCSK9
inhibitor
as
permitted
during
follow-up.
“It
almost
seems
as
though
hospitalization
represents
the
last
—
and
perhaps
only
—
opportunity
for
many
patients
to
gain
access
to
this
therapy,”
he
told
MedPage
Today.
It
was
ultimately
no
surprise
that
AMUNDSEN
was
unable
to
prove
a
clinical
benefit
to
immediate
PCSK9
inhibition,
others
experts
said.
“There
was
a
hypothesis
of
a
rapid
treatment
effect
emerging
and
kudos
to
the
investigators
for
testing
that.
But
the
reality
is
that
most
LDL-lowering
trials,
whether
they
were
with
statins
or
with
PCSK9
inhibitors,
showed
an
initial
lag
phase
before
a
clinical
benefit
emerged.
The
relative
risk
reduction
in
the
first
year
is
usually
smaller
than
in
subsequent
years,”
Shamir
Mehta,
MD,
MSc,
of
McMaster
University
and
Hamilton
Health
Sciences
in
Ontario,
Canada,
told
MedPage
Today.
“That,
coupled
with
the
modest
sample
size
and
the
fact
that
almost
all
patients
in
both
placebo
and
treatment
groups
received
high-intensity
statin
therapy
really
limits
the
ability
of
this
trial
to
show
meaningful
differences
in
clinical
outcomes.
A
pragmatic
trial
with
a
larger
sample
size
and
longer
term
follow-up
is
needed
for
that,”
said
Mehta,
who
was
not
involved
with
AMUNDSEN.
Sunil
Rao,
MD,
of
NYU
Langone
Health
in
New
York
City,
agreed
that
the
study
does
not
change
practice
given
these
limitations.
“I
think
studies
like
this
are
very
important
and
I
would
like
to
see
more
randomized
trials
of
lipid-lowering
therapies
in
patients
with
acute
coronary
syndrome,”
he
commented.
Indeed,
the
concept
of
very
early
PCSK9
inhibitor
administration
in
acute
MI
has
another
chance
to
advance
with
the
EVOLVE-MI
trial.
That
trial
has
already
exceeded
6,000
participants
and
boasts
a
longer
expected
follow-up
of
3.5-4
years.
AMUNDSEN
was
conducted
in
six
countries
and
enrolled
adults
with
high-risk
ST-elevation
MI
(STEMI;
age
>55)
or
non-ST-elevation
MI
(NSTEMI)
with
one
or
more
additional
high-risk
characteristics.
Montalescot’s
group
had
2,161
patients
randomized
1:1
to
receive
evolocumab
140
mg
subcutaneously
every
2
weeks
for
1
year
(first
injection
before
PCI)
or
standard
care
alone.
Standard
care
included
high-intensity
oral
lipid-lowering
therapy
with
the
option
of
PCSK9
inhibitor
use
per
guideline
indication.
Across
these
patients,
mean
age
was
67,
79%
were
men,
and
the
split
between
STEMI
and
NSTEMI
was
58%
and
42%,
respectively.
Mean
LDL
cholesterol
at
admission
was
116
mg/dL.
At
6
weeks,
this
fell
to
16
mg/dL
with
upfront
evolocumab
and
56
mg/dL
with
standard
care.
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