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good afternoon everybody thank you for
joining me today my name is Christine
wreckin Berg and I am a 2018 graduate of
st. Louis College of Pharmacy in the
current pgy one resident with the
college in the st. Louis County
Department of Public Health again thank
you for joining me to discuss the new
guidelines that provide recommendations
for aspirin for primary prevention of
cardiovascular disease I hope this
presentation is informative for everyone
if anyone has any questions I will save
time at the end to address them you
should have a questions box on your
screen feel free to type the questions
in there as they arise I have no
conflicts of interest to disclose my
goal is at bat at the completion of this
presentation you will be able to define
recommendations in the 2019 accha
guidelines for primary prevention of
cardiovascular disease throughout this
presentation I will use a number of
different abbreviations they are listed
here for your reference should you need
them before we get started I just want
to provide a brief overview of what we
will be covering today we will start off
with some background information then
move into some key recommendations from
the guidelines and lastly we will move
into recently published literature that
led to some of these new recommendations
regarding aspirin use for primary
prevention we will start first with some
of the general background information
cardiovascular disease is a serious
problem and has become the world's
number one killer approximately
seventeen point nine million people die
each year from cardiovascular disease
which is about one third of all deaths
worldwide more than 75 percent of these
deaths occur in low-income and
middle-income countries with 85% of
these being due to heart attack and
strokes we are all
probably aware of what cardio that
cardiovascular disease is but as a brief
reminder this condition is a group of
disorders of the heart and blood vessels
and can include a number of different
conditions
this can be disease as impacting blood
vessels that supply the heart muscle of
the brain and the arms and legs it can
be due to damage to the heart muscle or
valves or due to malformations of the
heart or even blood clots as mentioned
on the previous slide heart attacks and
strokes are two of the most common
causes of death from cardiovascular
disease due to loss of blood flow to the
heart or brain one of the most common
causes for this lack of blood flow is to
build up a fatty deposits within the
blood vessels this can be due in part to
a number of different risk factors these
include a number of modifiable risk
factors such as unhealthy lifestyles
which can include things like an
inadequate diet and lack of physical
activity that can contribute to weight
gain and obesity additional factors
include uncontrolled chronic disease
states such as diabetes hyperlipidemia
and hypertension lastly these modifiable
factors can include social factors such
as tobacco use one of the focuses of the
2019 accha guidelines for primary
prevention of cardiovascular disease is
the management of these modifiable risk
factors we will briefly discuss some of
the risk factor management here we will
start first with the lifestyle
recommendations
these include diet and exercise the new
guidelines recommend a plant-based and
Mediterranean diet with increased fruit
and not vegetable legume and lean animal
protein with high fiber as this has been
associated with a lower risk of
all-cause mortality compared to standard
diets exercise is also a cornerstone in
improving cardiovascular health the
guidelines recommend that adults engage
in at least 150 minutes of moderate
intensity or 75 minutes of vigorous
intensity aerobic physical activity or
an equivalent combination of moderate
and vigorous activity per week to
decrease a/s CVD risk additional risk
factor modification involves controlling
weight which can be assisted through
diet and exercise gaining adequate
control of diabetes hypertension and
blood cholesterol as well as focusing on
smoking cessation to decrease ascd risk
these guideline recommendations bring us
to our first key takeaway which is to
focus on a risk factor management to
help decrease the risk of developing
cardiovascular disease now that we have
reviewed a risk factor modification
we'll newel transition into a discussion
regarding aspirin for primary prevention
before jumping into the guideline
recommendations and supporting
literature I first would like to review
some definitions on the Left we have
risk factors for bleeding that are
defined in the guidelines these include
history of GI bleeding peptic ulcer
disease or bleeding from other sites age
greater than 70 years old
thrombocytopenia coagulopathy CKD and
concurrent use of other medications that
increase bleeding risk
additionally the guidelines to find
low-dose aspirin as 75 to 100 milligrams
by mouth daily and the pooled cohort
equation is recommended to be used to
calculate the ten-year AAS CVD risk
before we can determine if it is
appropriate to initiate an agent whether
that be statins or low-dose aspirin for
primary prevention of cardiovascular
disease it is necessary to determine the
patient's cardiovascular risk the
guidelines recommend that if a patient
is between the ages of 20 and 39 that
traditional AAS CVD risk factors be
assessed every four to six years
additionally a lifetime risk can also be
calculated for this patient population
and for those individuals between the
ages of 40 and 75 the tenure AAS CVD
risk should be calculated using the
pooled cohort equation for those
patients that are at a borderline ER in
a media AS CVD risk it is appropriate to
consider a number of different
additional risk factors such as coronary
artery calcium scoring and chronic
disease states some of which are listed
to assist in determining the
appropriateness of an agent for primary
prevention of a s CVD this brings us to
our second key takeaway of the important
importance of assessing a s CVD risk
prior to making decisions about
preventative and herve interventions
whether that be statins or aspirin now
we will focus on the newer literature
that explores some of the specific
patient populations that we may consider
aspirin for primary prevention there
were a number of new trials that were
published late last year in early this
year that focus on different aspects of
aspirin use for primary prevention the
first one here is the Esprit trial which
focused on a healthy elderly patient
population
the Araya trial focused on a younger
patient population with a moderate a.s
CVD risk and the ascend trial focused
specifically on patients with diabetes
and the last listed here as a
meta-analysis that was published earlier
this year that examined a number of
different randomized control trials that
evaluated the use of aspirin for primary
prevention the first study we will go
over is the Esprit trial that was
published as three separate publications
in the New England Journal of Medicine
last year the aim of this study was to
clarify the role of aspirin in the
healthy older adult patient population
this was a multicenter double-blind
placebo-controlled trial that followed
patients for a median of four point
seven years and included roughly 19,000
patients that were randomized to either
aspirin 100 milligrams daily or placebo
as mentioned the study focused on the
elderly patient population and therefore
only included patients that were at
least 70 years old it also focused on
those that did not have pre-existing
cardiovascular disease dementia or
disability and excluded those patients
that were known to be at a baseline high
risk of bleeding the primary outcome of
this study was a composite of death
dementia or persistent physical
disability secondary outcomes included a
composite of fatal coronary heart
disease non-fatal MI fatal or non-fatal
stroke or hospitalization for heart
failure the primary safety outcome was
major hemorrhage when looking at the
results of the primary endpoint you can
see here that there was no difference in
the composite of death dementia or
persistent physical disability but they
non statistically significant hazards
ratio of 1.01 in addition there were no
differences in the secondary efficacy
outcomes however we do see a difference
between the aspirin and placebo groups
in terms of major hemorrhage patients in
the aspirin group were 38% more likely
to experience a major hemorrhage than
those receiving placebo the study does
have some limitations such as low
inherence rates lower rates of
cardiovascular disease the unexpected
and limited external validity but
overall the Esprit trial shows us the
aspirin does not improve disability free
survival but does increase major
bleeding compared with placebo and an
elderly healthy patient population the
results of the Esprit trial assisted in
the development of the recommendation
that low-dose aspirin should not be
administered on a routine basis for the
primary prevention of a SC VD among
adults greater than 70 years of age ii
recently published randomized control
trial is the arrive trial that was
published in Lancet and 2018 this trial
was designed to help further clarify the
role of aspirin specifically in a
patient population that is at a baseline
moderate risk for developing after a
sclerotic cardiovascular disease the
study was a multicenter double-blind
placebo-controlled trial that followed
up with patients for a median of 5 years
it included roughly 12,500 patients that
were randomized to ask from 100
milligrams daily or placebo as mentioned
the patient population included patients
at a moderate cardiovascular risk and
excluded those with histories of
vascular events those receiving
concomitant antiplatelet therapy and
those that had a high bleeding risk or
pre-existing diabetes the primary
outcome was a composite of time to first
occur in
have confirmed mi stroke cardiovascular
death unstable angina or TI a secondary
outcomes included a composite of time to
first occurrence of cardiovascular death
MI or stroke and individual components
of the primary outcome there was not a
statistically significant difference
between the aspirin and placebo groups
in terms of the primary outcome but they
not statistically significant hazard
ratio of 0.96 there were also no
statistically significant differences in
the intention-to-treat population for
any of the secondary efficacy endpoints
however when looking at the safety in
points there was a statistically
significant increase in GI bleeding and
patients in the aspirin group compared
to those in the placebo group but they
hazards ratio of two point one one the
bottom line from the study is that
despite the limitations of
lower-than-expected event rates lemonade
external validity and exclusion of
patients with diabetes aspirin does not
provide a benefit in patients that that
are adding moderate a.s CVD risk but
does place them at an increased bleeding
risk so the last of the recently
published randomized control trials is
the essential that was published in the
New England Journal of Medicine in 2018
but evaluated patients who may be at a
baseline increased risk of a s CVD due
to diabetes the objective of this study
was to evaluate the use of low-dose
aspirin in a population of patients with
diabetes without pre-existing
cardiovascular disease similar to the
previous two studies this was a
multicenter double-blind
placebo-controlled trial that followed
patients for approximately seven years
thus included roughly fifteen thousand
five hundred patients that were
randomized to aspirin 100 milligrams
daily or placebo as mentioned earlier
all included patients had a diagnosis of
diabetes they were also at least 40
years old and did not have pre-existing
cardiovascular disease the primary
outcome was the composite of time to
first non-fatal MI non-fatal stroke
excluding confirmed intracranial
hemorrhage TI a or death from any
vascular cause excluding confirmed
intracranial hemorrhage her safety
outcomes this
we also evaluated the first occurrence
of any major bleeding event
I'm looking at the results of the
primary endpoint aspirin was associated
with a 12% relative reduction in major
cardiovascular events as compared to
placebo as you can see here with a
statistically significant rate ratio of
0.88 the primary safety in point
indicated that aspirin was not heard
after was associated with a 29% increase
in major bleeding as compared to placebo
group with a rate ratio of one point two
nine that was also statistically
significant overall the study had a
number needed to treat of 91 and a
number needed to harm of 112 indicating
that although there was a statistically
significant benefit and the primary
efficacy outcome the gap between the
relative benefit and the relative harm
was narrow one major limitation of the
study was that it did not have a large
representation of patients at a higher
cardiovascular risk indicating that a
blanket seam that cannot be made for
patients with diabetes regarding aspirin
use for primary prevention rather the
decision needs to be made on a patient
by patient basis focusing on
cardiovascular disease risk
consider a brief review of recently
published literature we can look at the
systematic review and meta-analysis
analysis published by Zhang and
colleagues in JAMA and January of this
year the purpose of the study was to
help further assess the association of
aspirin use for primary prevention with
cardiovascular events and bleeding the
study included a total of 13 randomized
controlled trials and over 150,000
patients with no known pre-existing
cardiovascular disease the primary
outcome was a composite of
cardiovascular mortality non-fatal MI
and non-fatal stroke which could be
ischemic or hemorrhagic patients
receiving aspirin for primary prevention
were 11% less likely to experience a
cardiovascular event and those in the
control group with a statistically
significant has a ratio the primary
safety outcome was major bleeding
patients in the aspirin group were 43
percent more likely to develop major
bleeding than those in the placebo group
with a statistically significant hazard
ratio here the number needed to treat
was 265 and the number needed to harm
was 210 indicating that more patients
would be harmed by a major bleeding
event than those that would prevent a
cardiovascular event now that we
reviewed additional primary literature
this brings us to our final two
takeaways when we consider our older
trial data and in combination with all
of these recent studies it leads us to
question the benefit of low-dose aspirin
for primary prevention of cardiovascular
disease for this reason the new
recommendations by the accha guideline
is that low-dose aspirin can be
considered in patients forty to seventy
years of age at a higher AAS CVD risk
and low bleed risk this recommendation
now has a lower level of evidence at
class 2b and is characterized by removal
of a specific AS CVD risk or for
inclusion for aspirin consideration
meaning that instead the whole patient
picture should be considered including a
s CVD risk scores additional risk
enhancement factors and patient and
clinician preference especially when we
take into consideration the results of
the arrive and ascend trials the use of
aspirin in patients at a moderate ased
risk needs to be individualized lastly
all of those studies we reviewed today
and decay
that aspirin use places patients at an
increased lead risk compared to those
receiving placebo leading to the
continued recommendation that aspirin
should not be used for primary
prevention regardless of age and adults
who are at an increased lead risk
I hope these takeaways have been helpful
and providing a quick update to the new
accha guideline for the primary
prevention of cardiovascular disease now
that we've completed the presentation
portion of the webinar I'd like to move
into a few brief assessment questions I
will start by reading the question and
the answers and I will give you a moment
to think about the answer and you can
type your choice into the question box
so that I can see your response then we
will review the correct choice so first
which trial showed no difference in
cardiovascular disease composite
endpoint in the population of patients
70 years of age or older so a this free
trial be the arrive trial or see the
ascend trial
the correct answer is a the S free trial
so these free trial included healthy
patients that were 70 years of age or
older
the secondary end point of the study was
a composite of cardiovascular disease
which included fatal coronary heart
disease non-fatal in mine
fatal or non-fatal stroke or
hospitalization for heart failure which
was not found to be statistically
significant with the hazard ratio 0.95
this brings us to our final assessment
question play 75 year old white male
patient with no significant past medical
history is considering initiating
aspirin 81 milligrams daily for primary
prevention of a heart attack based on
the 2019 accha guidelines for primary
prevention of cardiovascular disease
what is the best recommendation say a
low dose aspirin may be considered if
the patient is not at a high leading
risk the low dose aspirin should not be
considered or see low dose aspirin is
recommended and the correct answer is B
low dose aspirin should not be
recommended
so that 2019 accha guidelines provide
new recommendations for aspirin use in
the older patient population according
to the guidelines low dose aspirin at 75
to 100 milligrams daily should not be
administered on a routine basis for the
primary prevention of a s CVD among
adults over the age of 70 that concludes
the presentation what questions do you
have
okay it looks like there are not any
questions I apologize again for the
problems with the technology here I did
want to let you know that within an hour
you should receive an email with the
details on how you can obtain CEU credit
for participating in this activity thank
you again