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2. Recommendation Topics
3. Recommendation: Aspirin Use to Prevent Cardiovascular Disease: Preventive
Medication
4. Recommendation: Aspirin Use to Prevent Cardiovascular Disease: Preventive
Medication

FINAL RECOMMENDATION STATEMENT

ASPIRIN USE TO PREVENT CARDIOVASCULAR DISEASE: PREVENTIVE MEDICATION

APRIL 26, 2022

Recommendations made by the USPSTF are independent of the U.S. government. They
should not be construed as an official position of the Agency for Healthcare
Research and Quality or the U.S. Department of Health and Human Services.

Read the Full Recommendation Statement Download (PDF)

RECOMMENDATION SUMMARY

Population Recommendation Grade Adults aged 40 to 59 years with a 10% or greater
10-year cardiovascular disease (CVD) risk The decision to initiate low-dose
aspirin use for the primary prevention of CVD in adults aged 40 to 59 years who
have a 10% or greater 10-year CVD risk should be an individual one. Evidence
indicates that the net benefit of aspirin use in this group is small. Persons
who are not at increased risk for bleeding and are willing to take low-dose
aspirin daily are more likely to benefit. C Adults 60 years or older The USPSTF
recommends against initiating low-dose aspirin use for the primary prevention of
CVD in adults 60 years or older. D

CLINICIAN SUMMARY

Expand All

What does the USPSTF recommend? For adults aged 40 to 59 years with an estimated
10% or greater 10-year cardiovascular disease (CVD) risk:
The decision to initiate low-dose aspirin use for the primary prevention of CVD
in this group should be an individual one.
Grade: C

For adults 60 years or older:
Do not initiate aspirin for the primary prevention of CVD.
Grade: D

To whom does this recommendation apply? This recommendation applies to adults 40
years or older without signs or symptoms of CVD or known CVD and who are not at
increased risk for bleeding (eg, no history of gastrointestinal ulcers, recent
bleeding, or other medical conditions, or taking medications that increase
bleeding risk). What’s new?
* The USPSTF has changed the age ranges and grades of its recommendation on
aspirin use.
* The USPSTF currently recommends considering initiating aspirin in persons
with an estimated 10% or greater CVD risk at a younger age: 40 years instead
of 50 years.
* Aspirin should be initiated selectively based on individual decision-making
rather than routinely for all persons in the recommended age and CVD risk
group.
* There is a new recommendation not to initiate aspirin in adults 60 years or
older for primary prevention.
* The evidence is unclear whether aspirin use reduces the risk of colorectal
cancer incidence or mortality.

How to implement this recommendation?
* Consider the patient’s age.
* For adults aged 40 to 59 years: Estimate CVD risk using a CVD risk estimator.
* In patients whose estimated CVD risk is 10% or greater, use shared
decision-making, taking into account potential benefits and harms of
aspirin use, as well as patients’ values and preferences, to inform the
decision about initiating aspirin.
* For patients initiating aspirin use, it would be reasonable to use a dose
of 81 mg/day.
* For adults 60 years or older: Do not initiate aspirin for primary prevention
of CVD.

What additional information should clinicians know about this recommendation?
* Age is one of the strongest risk factors for CVD.
* Males have a higher prevalence of CVD than females. Among both sexes, Black
persons have the highest prevalence of CVD.
* Aspirin reduces the risk of cardiovascular events, but it increases the risk
for gastrointestinal bleeding, intracranial bleeding, and hemorrhagic stroke.
* Both CVD risk and risk for gastrointestinal bleeding, intracranial
hemorrhage, and hemorrhagic stroke (with or without aspirin use) increase
with age.
* For patients who are eligible and choose to start taking aspirin, the
benefits become smaller with advancing age, and data suggest that clinicians
and patients should consider stopping aspirin use around age 75 years.

Why is this recommendation and topic important? CVD is the leading cause of
mortality in the US, accounting for more than 1 in 4 deaths. Each year, an
estimated 605,000 Americans have a first heart attack and about 610,000
experience a first stroke. What are additional tools and resources?
* The Million Hearts initiative provides information on improving
cardiovascular health and preventing heart attack and stroke at
https://millionhearts.hhs.gov/
* The Centers for Disease Control and Prevention have resources related to risk
of heart disease and the prevention of heart disease for patients and health
professionals at https://www.cdc.gov/heartdisease/index.htm
* The National Heart, Lung, and Blood Institute has patient resources related
to coronary heart disease at
https://www.nhlbi.nih.gov/health-topics/coronary-heart-disease

Where to read the full recommendation statement? Visit the USPSTF website
(https://www.uspreventiveservicestaskforce.org/uspstf/) or the JAMA website
(https://jamanetwork.com/collections/44068/united-states-preventive-services-task-force)
to read the full recommendation statement. This includes more details on the
rationale of the recommendation, including benefits and harms; supporting
evidence; and recommendations of others

The USPSTF recognizes that clinical decisions involve more considerations than
evidence alone. Clinicians should understand the evidence but individualize
decision-making to the specific patient or situation.

* View the Clinician Summary in PDF

ADDITIONAL INFORMATION

* Supporting Evidence
* Related Resources & Tools

* Final Evidence Review (April 26, 2022)
* Final Modeling Report (April 26, 2022)
* Evidence Summary (April 26, 2022)
* Modeling Study (April 26, 2022)
* Final Research Plan (May 14, 2020)

Tools
* Let's Talk About It: Starting Aspirin to Prevent Heart Disease and Stroke A
Discussion Guide for Healthcare Professionals and Patients - Educational
Tools
* Coronary Heart Disease (National Heart, Lung, and Blood Institute) - For
Providers
* Prevent Heart Disease (Centers for Disease Control and Prevention) - For
Providers
* Million Hearts Initiative - For Providers

Related Resources
* JAMA Patient Page: Use of Aspirin to Prevent Cardiovascular Disease
* JAMA Podcast: Aspirin Use for Cardiovascular Disease

RECOMMENDATION INFORMATION

Table of Contents PDF Version and JAMA Link Archived Versions
* Importance
* Practice Considerations
* Update of Previous USPSTF Recommendation
* Supporting Evidence
* Research Needs and Gaps
* Recommendations of Others
* Members of the US Preventive Services Task Force
* Copyright and Source Information

* View the Recommendation in PDF Format

To read the recommendation statement in JAMA, select here.

To read the evidence summary in JAMA, select here.

To read the modeling study in JAMA, select here.

* (April 2016)
* (March 2009)
* (March 2007)
* (January 2002)
* (January 1996)

FULL RECOMMENDATION:

Expand All
Importance

Cardiovascular disease (CVD) is the leading cause of mortality in the US,
accounting for more than 1 in 4 deaths.1 Each year, an estimated 605,000 people
in the US have a first myocardial infarction and an estimated 610,000 experience
a first stroke.2

USPSTF ASSESSMENT OF MAGNITUDE OF NET BENEFIT

The US Preventive Services Task Force (USPSTF) concludes with moderate certainty
that aspirin use for the primary prevention of CVD events in adults aged 40 to
59 years who have a 10% or greater 10-year CVD risk has a small net benefit.

The USPSTF concludes with moderate certainty that initiating aspirin use for the
primary prevention of CVD events in adults 60 years or older has no net benefit.

See the Table for more information on the USPSTF recommendation rationale and
assessment. For more details on the methods the USPSTF uses to determine the net
benefit, see the USPSTF Procedure Manual.3

Return to Table of Contents
Practice Considerations

PATIENT POPULATION UNDER CONSIDERATION

This recommendation applies to adults 40 years or older without signs or
symptoms of CVD or known CVD (including history of myocardial infarction or
stroke) who are not at increased risk for bleeding (eg, no history of
gastrointestinal ulcers, recent bleeding, other medical conditions, or use of
medications that increase bleeding risk). In this recommendation statement, CVD
risk and the net benefits of aspirin use are discussed using the terms “men” and
“women,” although it is likely that CVD risk and net benefit estimates are
driven by sex (ie, male/female) rather than gender identity.

ASSESSMENT OF RISK

CVD RISK

Older age is one of the strongest risk factors for CVD. Men have a higher
overall CVD disease burden, although women experience higher mortality from
certain cardiovascular events, such as stroke. Men tend to experience CVD events
earlier in life compared with women. The burden of CVD also differs by race and
ethnicity. Among both sexes, Black persons have the highest prevalence of CVD.2

The American College of Cardiology/American Heart Association (ACC/AHA) Pooled
Cohort Equations may be used to estimate 10-year risk of CVD. The ACC/AHA risk
estimator is, to date, the only US-based CVD risk prediction tool that has
published external validation studies in other US-based populations.4 The
estimator has separate equations based on sex and for Black persons and
non-Black persons, which include the risk factors of age, cholesterol levels,
systolic blood pressure level, antihypertension treatment, presence of diabetes,
and smoking status, and focuses on hard clinical outcomes (myocardial infarction
and death from coronary heart disease; ischemic stroke and stroke-related death)
as the outcomes of interest. It is important to note that increasing age heavily
influences the ACC/AHA estimated 10-year CVD event risk. The risk prediction
equations generally show higher risk for Black persons than White persons.4 The
USPSTF recognizes that race is a social construct and an imperfect proxy for
social determinants of health and the effects of structural racism. Concerns
about calibration exist, with many external validation studies showing
overprediction in broad populations (men and women across racial and ethnic
groups).5-7 Limited evidence also suggests underprediction in disadvantaged
communities8,9 that could lead to underutilization of preventive therapies.
Clinicians should recognize that predictions of 10-year CVD events using the
Pooled Cohort Equations are estimates.

BLEEDING RISK

The risk for gastrointestinal bleeding, intracranial hemorrhage, and hemorrhagic
stroke, with or without aspirin use, increases with older age. Other risk
factors include male sex, diabetes, history of gastrointestinal issues (such as
peptic ulcer disease), liver disease, smoking, and elevated blood pressure.
Certain medications, including nonsteroidal anti-inflammatory drugs, steroids,
and anticoagulants, increase the risk of bleeding.10-13 These risk factors
should be considered in the overall decision about whether to start or continue
aspirin therapy.

TREATMENT OR INTERVENTION

The benefits of aspirin for CVD prevention appear similar for a low dose (≤100
mg/d) and for all doses that have been studied in CVD prevention trials (50 to
500 mg/d).14 A pragmatic approach would be to use 81 mg/d, which is the most
commonly prescribed dose in the US.

IMPLEMENTATION

Because CVD risk estimation is imprecise and imperfect at the individual level,
the USPSTF suggests using these risk estimates as a starting point to discuss
with appropriate candidates their desire for daily aspirin use. The benefits of
initiating aspirin use are greater for individuals at higher risk for CVD events
(eg, those with >15% or >20% 10-year CVD risk).

In addition to age and estimated level of CVD risk, decisions about initiating
aspirin use should be based on shared decision-making between clinicians and
patients about the potential benefits and harms. Persons who place a higher
value on the potential benefits (decreasing an individual’s risk of a myocardial
infarction or stroke) than the potential harms (the risk of gastrointestinal or
intracranial bleeding) may choose to initiate low-dose aspirin use. Persons who
place a higher value on the potential harms or the burden of taking a daily
preventive medication than on the potential benefits may choose not to initiate
low-dose aspirin use.

STOPPING AGE

Annual bleeding events in individuals without risk factors for increased
bleeding (eg, history of gastrointestinal bleeding risk, history of peptic ulcer
disease, or use of nonsteroidal anti-inflammatory drugs or corticosteroids) are
rare, but risk for bleeding increases modestly with advancing age.12 For persons
who have initiated aspirin use, the net benefits continue to accrue over time in
the absence of a bleeding event. The net benefits, however, generally become
progressively smaller with advancing age because of an increased risk for
bleeding, and modeling data suggest that it may be reasonable to consider
stopping aspirin use around age 75 years.

ADDITIONAL TOOLS AND RESOURCES

Million Hearts 2022 is a national initiative to prevent 1 million myocardial
infarctions and strokes within 5 years. It focuses on implementing a small set
of evidence-based priorities and targets that can improve cardiovascular health
for all (https://millionhearts.hhs.gov/).

The Centers for Disease Control and Prevention has resources related to risk of
heart disease and the prevention of heart disease for patients and health
professionals (https://www.cdc.gov/heartdisease/index.htm).

The National Heart, Lung, and Blood Institute has patient resources related to
coronary heart disease
(https://www.nhlbi.nih.gov/health-topics/coronary-heart-disease).

OTHER RELATED USPSTF RECOMMENDATIONS

The USPSTF has made several other recommendations on CVD prevention, including
statin use to prevent CVD,15 smoking cessation,16 counseling to promote a
healthful diet and physical activity in persons with and without cardiovascular
risk factors,17,18 and interventions to prevent obesity-related morbidity and
mortality,19 as well as screening for high blood pressure20 and diabetes.21 The
USPSTF has also made a recommendation on screening for colorectal cancer
(CRC).22

Return to Table of Contents
Update of Previous USPSTF Recommendation

This recommendation replaces the 2016 USPSTF recommendation on aspirin use to
prevent CVD and CRC.23 In 2016, the USPSTF recommended initiating low-dose
aspirin use for the primary prevention of CVD and CRC in adults aged 50 to 59
years who have a 10% or greater 10-year CVD risk, are not at increased risk for
bleeding, have a life expectancy of at least 10 years, and are willing to take
low-dose aspirin daily for at least 10 years, and that the decision to initiate
low-dose aspirin use in adults aged 60 to 69 years who have a 10% or greater
10-year CVD risk should be an individual one. The USPSTF previously found that
the evidence was insufficient to assess the balance of benefits and harms of
initiating aspirin use for the primary prevention of CVD and CRC in adults
younger than 50 years or adults 70 years or older.

For the current recommendation, the USPSTF has changed the age ranges and grades
of its recommendation on aspirin use. The USPSTF recommends that the decision to
initiate low-dose aspirin use for the primary prevention of CVD in adults aged
40 to 59 years who have a 10% or greater 10-year CVD risk should be an
individual one and recommends against initiating low-dose aspirin use for the
primary prevention of CVD in adults 60 years or older. Based on new trial
evidence,24 updated analyses of the evidence from primary CVD prevention
populations,14 and longer-term follow-up data from the Women’s Health Study
(WHS) (I.-M. Lee, ScD, Harvard Medical School, written communication, November
23, 2020), the USPSTF concluded that the evidence is inadequate that low-dose
aspirin use reduces CRC incidence or mortality.

Return to Table of Contents
Supporting Evidence

SCOPE OF REVIEW

To update its 2016 recommendation, the USPSTF commissioned a systematic review
on the effectiveness of aspirin to reduce the risk of CVD events (myocardial
infarction and stroke), cardiovascular mortality, and all-cause mortality in
persons without a history of CVD. The systematic review also investigated the
effect of aspirin use on CRC incidence and mortality in primary CVD prevention
populations, as well as the harms, particularly bleeding harms, associated with
aspirin use.14,25

In addition to the systematic evidence review, the USPSTF commissioned a
microsimulation modeling study to assess the net balance of benefits and harms
from aspirin use for primary prevention of CVD and CRC, stratified by age, sex,
and CVD risk level. Modeling study parameter inputs were informed by the results
of the systematic review, and the primary outcomes were net benefits expressed
as quality-adjusted life-years and life-years.26,27

BENEFITS OF PREVENTIVE MEDICATION

The USPSTF considered 13 randomized clinical trials (RCTs) involving 161,680
participants that reported on the benefits of aspirin use for the primary
prevention of cardiovascular morbidity and mortality.14,25 Most trials used
low-dose aspirin of 100 mg/d or less or aspirin every other day and included a
balanced number of male and female participants and a broad distribution of
ages, with mean age ranging from 53 years in the Physicians' Health Study28 to
74 years in the Aspirin in Reducing Events in the Elderly (ASPREE) trial.24

The evidence showed that aspirin use for primary prevention of CVD was
associated with a decreased risk of myocardial infarction and stroke but not
cardiovascular mortality or all-cause mortality. Results were similar when
including studies using all doses of aspirin compared with studies using
low-dose aspirin.14 Since low-dose aspirin is most relevant to current practice,
the analyses below report outcomes pooling studies of low-dose aspirin use.
Pooled effect estimates of studies using low-dose aspirin were also used to
inform the parameters and assumptions of the microsimulation modeling
study.26,27

A pooled analysis of 11 trials (n = 134,470) showed that low-dose aspirin use
was associated with a statistically significant decreased risk of nonfatal
myocardial infarction (Peto odds ratio [OR], 0.88 [95% CI, 0.80-0.96]).
Similarly, a pooled analysis of 5 trials (n = 54,947) demonstrated that low-dose
aspirin use was associated with a statistically significant decreased risk of
nonfatal ischemic stroke (Peto OR, 0.88 [95% CI, 0.78-1.00]; P = .046). Fatal
cardiovascular events were less common, so pooled analyses showed that low-dose
aspirin use was not associated with a statistically significant effect on fatal
myocardial infarction, fatal stroke, cardiovascular mortality, or all-cause
mortality (at 3.6 to 10.1 years of follow-up).14,25 Although evidence does not
suggest that the relative effect of aspirin on CVD outcomes is modified by
baseline CVD risk, the absolute magnitude of the benefit is greater in persons
at higher CVD risk.

New RCT data, as well as newly available information on the age distribution of
participants in the WHS, show that almost 22 000 participants younger than 50
years and more than 37,000 participants 70 years or older were included in the
CVD prevention trials. Most trials with age subanalyses did not find a
statistically significant difference in the relative effect of aspirin on CVD
outcomes by age.14,25 The USPSTF thus concluded that evidence on the benefits of
aspirin on CVD outcomes was adequate for all groups, including adults aged 40 to
49 years and adults 70 years or older.

The evidence review found fewer studies reporting on the effects of aspirin use
on CRC incidence or mortality. Four studies conducted in primary CVD prevention
populations found no association between aspirin use and CRC incidence at up to
approximately 10 years of follow-up.14,25 Only 1 trial, the WHS (n = 39,876),
reported on the effect of low-dose aspirin use on CRC incidence beyond 10 years
by including posttrial observational follow-up. Although the WHS reported a
lower incidence of CRC at 17.5 years of follow-up (Peto OR, 0.82 [95% CI,
0.69-0.98]),29 recent data showed that this effect did not persist from 17.5 to
26 years of follow-up (I.-M. Lee, ScD, Harvard Medical School, written
communication, November 23, 2020). Two RCTs, ASPREE24 and WHS (I.-M. Lee, ScD,
Harvard Medical School, written communication, November 23, 2020), reported CRC
mortality during the trial phase. ASPREE reported that aspirin use was
associated with statistically significantly higher CRC mortality at 4.7 years of
follow-up (Peto OR, 1.74 [95% CI, 1.02-2.95]), while the WHS did not find a
statistically significant increase in CRC mortality at 10 years. When including
observational follow-up beyond the trial phase, 2 trials of low-dose aspirin use
reported reductions in CRC mortality. In the Thrombosis Prevention Trial30,31
(n = 5085), low-dose aspirin use was associated with a statistically significant
lower risk of CRC mortality at 18.3 years of follow-up (Peto OR, 0.62 [95% CI,
0.41-0.94]), and the WHS reported lower CRC mortality at 17.5 years of follow-up
that was not statistically significant (Peto OR, 0.86 [95% CI, 0.64-1.16]) and
was attenuated from 17.5 to 26 years of follow-up (I.-M. Lee, ScD, Harvard
Medical School, written communication, November 23, 2020).

The body of evidence on the effects of aspirin use on CRC incidence and
mortality is limited by several factors. Overall, only a small number of trials
reported on CRC outcomes. The ASPREE trial in older adults found aspirin use to
be associated with an increased risk of CRC mortality.24 Although this finding
does not constitute firm evidence that aspirin use is associated with increased
risk of CRC mortality, it is one factor that calls into question whether aspirin
use has a beneficial effect on CRC outcomes. Longer-term follow-up data
suggesting that aspirin use is associated with lower CRC risk is heavily
weighted by 1 trial conducted in women only, and the evidence on CRC mortality
is limited by few CRC deaths. Additionally, posttrial follow-up data may be
subject to biases, and in some cases, CRC outcomes data were collected by
outside investigators.14,25

HARMS OF PREVENTIVE MEDICATION

The USPSTF reviewed 14 RCTs in CVD primary prevention populations that reported
on the bleeding harms of aspirin. Studies reported a variety of outcomes,
including total major bleeds (defined as a composite of intracranial hemorrhage,
major gastrointestinal bleeding, or major bleeding from other sites), major
gastrointestinal bleeds (defined as a gastrointestinal bleed that required a
transfusion, hospital admission, or resulted in death), extracranial bleeds
(defined as major bleeding that was not intracranial), hemorrhagic stroke, and
intracranial bleeds (defined as hemorrhagic stroke, subarachnoid hemorrhage, and
subdural hemorrhage).14,25

When looking at studies reporting on the harms of low-dose aspirin use (≤100
mg/d), which is most relevant to current practice, a pooled analysis of 10
trials (n = 119,130) showed that aspirin use was associated with a 58% increase
in major gastrointestinal bleeding (Peto OR, 1.58 [95% CI, 1.38-1.80]). A pooled
analysis of 11 trials (n = 134,470) showed an increase in intracranial bleeds in
the aspirin group compared with the control group (Peto OR, 1.31 [95% CI,
1.11-1.54]). Low-dose aspirin use was not associated with a statistically
significant increase in risk of fatal hemorrhagic stroke.14,25

Data suggest that the increased incidence of bleeding associated with aspirin
use occurs relatively quickly after initiating aspirin, and data do not suggest
that aspirin has a differential relative bleeding risk based on age, sex,
presence of diabetes, level of CVD risk, or race or ethnicity.14,25 Although the
increase in relative risk does not appear to differ based on age, the absolute
incidence of bleeding, and thus the magnitude of bleeding harm, increases with
age, and more so in adults 60 years or older. Because of the very small number
of fatal gastrointestinal bleeding events in trials and inconsistent reporting,
it is uncertain whether aspirin use increases fatal gastrointestinal
bleeding.14,25

ESTIMATE OF MAGNITUDE OF NET BENEFIT

The USPSTF commissioned a microsimulation model to estimate the magnitude of net
benefit of low-dose aspirin use.26,27 The model incorporated findings from the
systematic review to inform its parameters and assumptions, including that daily
low-dose (≤100 mg/d) aspirin use reduces the risk of nonfatal myocardial
infarction and nonfatal stroke, increases the risk of major gastrointestinal
bleeding and intracranial hemorrhage, and has no effect on the risk of CVD
mortality. As there was insufficient evidence that aspirin use reduces CRC
incidence, the modeling study base case assumed no effect of aspirin on CRC
incidence.

Modeling outcomes were stratified by age, decade of aspirin initiation (40-49
years, 50-59 years, 60-69 years, and 70-79 years), sex, and baseline 10-year CVD
risk level (5% to 20%). When combined with primary trial data and pooled
analyses from the systematic evidence review, the model provided additional
information to assess the balance of benefits and harms of aspirin use. The
primary model outcomes were net quality-adjusted life-years and life-years
gained or lost over a lifetime as a result of aspirin use. Also considered was
the effect of stopping aspirin that had been initiated for primary prevention
over 5-year age intervals from ages 65 to 85 years.26,27

Modeling data estimated that aspirin use in both men and women aged 40 to 59
years with 10% or greater 10-year CVD risk generally provides a modest net
benefit in both quality-adjusted life-years and life-years gained. Initiation of
aspirin use in persons aged 60 to 69 years results in quality-adjusted
life-years gained that range from slightly negative to slightly positive
depending on CVD risk level, and life-years gained are generally negative. In
persons aged 70 to 79 years, initiation of aspirin use results in a loss of both
quality-adjusted life-years and life-years at essentially all CVD risk levels
modeled (ie, up to 20% 10-year CVD risk) (Figure).26,27 The USPSTF thus
determined that aspirin use has a small net benefit in persons aged 40 to 59
years with 10% or greater 10-year CVD risk and that initiation of aspirin use
has no net benefit in persons 60 years or older.

When looking at net lifetime benefit of continuous aspirin use until stopping at
age 65, 70, 75, 80, or 85 years, modeling data suggested that there is generally
little incremental lifetime net benefit in continuing aspirin use beyond the age
of 75 to 80 years.26,27 It is important to note that the net benefit of
continuing aspirin use by persons in their 60s or 70s is not the same as the net
benefit of initiating aspirin use by persons in their 60s or 70s. This is
because, in part, CVD risk is heavily influenced by age. Persons who meet the
eligibility criteria for aspirin use at a younger age (ie, ≥10% 10-year CVD risk
in their 40s or 50s) typically would have even higher CVD risk by their 60s or
70s compared with persons who first reach a 10% or greater 10-year CVD risk in
their 60s or 70s and may gain more benefit by continuing aspirin use than
persons at lower risk might gain by initiating aspirin use.

HOW DOES EVIDENCE FIT WITH BIOLOGICAL UNDERSTANDING?

Aspirin’s mechanism of action to promote CVD prevention is well known. At lower
doses, aspirin is an irreversible cyclooxygenase 1 (COX-1) enzyme inhibitor. At
higher doses, aspirin also inhibits COX-2. Aspirin reduces the risk for
atherothrombosis through the inhibition of platelet function (through COX-1
inhibition) and has been used widely for the prevention of CVD events,
particularly for secondary prevention.32 The COX-1 enzyme is also responsible
for producing a variety of prostaglandins that protect the gastrointestinal
mucosa.33 By inhibiting this enzyme, aspirin use can promote gastrointestinal
bleeding.34 The mechanism for the possible antineoplastic effects of aspirin is
not as well understood.14

RESPONSE TO PUBLIC COMMENT

A draft version of this recommendation statement was posted for public comment
on the USPSTF website from October 12 to November 8, 2021. In response to public
comment, the USPSTF wants to restate that the focus of this recommendation is
the use of aspirin for the primary prevention of CVD and not for other
indications. This recommendation only applies to persons who do not have a
history of CVD, signs or symptoms of CVD, or other conditions for which aspirin
may be indicated. Persons who are currently taking aspirin and have questions
about why they are taking it, or whether they should continue or discontinue
aspirin use, should discuss these questions with their clinician. Persons who
are taking aspirin should not discontinue using it without consulting their
clinician. For persons who are deciding with their clinician whether to continue
or discontinue taking aspirin for primary prevention, clinicians may want to
consider that person’s age, level of CVD risk and bleeding risk, preferences,
and reasons for taking aspirin.

In response to public comment, the USPSTF clarified language about its
assessment of the precision of CVD risk assessment and added information on
factors that can be considered by clinicians and patients as they engage in
shared decision-making about the initiation of aspirin use. Information on the
evidence the USPSTF reviewed on the effect of aspirin on CRC incidence and
mortality and how it considered the findings from the ASPREE trial can also be
found in the Supporting Evidence section of this recommendation. Also, in
response to public comment, the USPSTF wants to note that it did not review the
emerging evidence on the effect of aspirin on COVID-19, the disease caused by
the coronavirus SARS-CoV-2.

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Research Needs and Gaps

More research is needed to evaluate the following.

* Improving the accuracy of CVD risk prediction in all racial and ethnic and
socioeconomic groups.
* The gastrointestinal bleeding risk associated with aspirin use in populations
representative of the US primary CVD prevention population.
* Characterizing the distribution of patient preferences across the spectrum of
cardiovascular risk after patients are informed about the benefits and harms
of aspirin.
* The effects of low-dose aspirin use on CRC incidence and mortality over the
long term (10 to 20 years and longer) in primary prevention populations and
in the context of current CRC screening practices.

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Recommendations of Others

The ACC/AHA recommends that low-dose aspirin use (75 to 100 mg/d) might be
considered for the primary prevention of atherosclerotic CVD among select adults
aged 40 to 70 years at higher CVD risk but not at increased risk of bleeding.
Low-dose aspirin use is not recommended on a routine basis for primary
prevention of CVD in adults older than 70 years or among adults of any age who
are at increased risk of bleeding.35 The American Academy of Family Physicians
supports the 2016 USPSTF recommendation on aspirin use.36

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Members of the US Preventive Services Task Force

The US Preventive Services Task Force members include the following individuals:
Karina W. Davidson, PhD, MASc (Feinstein Institutes for Medical Research at
Northwell Health, Manhasset, New York); Michael J. Barry, MD (Harvard Medical
School, Boston, Massachusetts); Carol M. Mangione, MD, MSPH (University of
California, Los Angeles); Michael Cabana, MD, MA, MPH (Albert Einstein College
of Medicine, New York, New York); David Chelmow, MD (Virginia Commonwealth
University, Richmond); Tumaini Rucker Coker, MD, MBA (University of Washington,
Seattle); Esa M. Davis, MD, MPH (University of Pittsburgh, Pittsburgh,
Pennsylvania); Katrina E. Donahue, MD, MPH (University of North Carolina at
Chapel Hill); Carlos Roberto Jaén, MD, PhD, MS (University of Texas Health
Science Center, San Antonio); Alex H. Krist, MD, MPH (Virginia Commonwealth
University, Richmond); Martha Kubik, PhD, RN (George Mason University, Fairfax,
Virginia); Li Li, MD, PhD, MPH (University of Virginia, Charlottesville); Gbenga
Ogedegbe, MD, MPH (New York University, New York, New York); Lori Pbert, PhD
(University of Massachusetts Medical School, Worcester); John M. Ruiz, PhD
(University of Arizona, Tucson); James Stevermer, MD, MSPH (University of
Missouri, Columbia); John B. Wong, MD (Tufts University School of Medicine,
Boston, Massachusetts).

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Copyright and Source Information

Conflict of Interest Disclosures: Authors followed the policy regarding
conflicts of interest described at
https://uspreventiveservicestaskforce.org/uspstf/about-uspstf/conflict-interest-disclosures.
All members of the USPSTF receive travel reimbursement and an honorarium for
participating in USPSTF meetings.

Funding/Support: The USPSTF is an independent, voluntary body. The US Congress
mandates that the Agency for Healthcare Research and Quality (AHRQ) support the
operations of the USPSTF.

Role of the Funder/Sponsor: AHRQ staff assisted in the following: development
and review of the research plan, commission of the systematic evidence review
from an Evidence-based Practice Center, coordination of expert review and public
comment of the draft evidence report and draft recommendation statement, and the
writing and preparation of the final recommendation statement and its submission
for publication. AHRQ staff had no role in the approval of the final
recommendation statement or the decision to submit for publication.

Disclaimer: Recommendations made by the USPSTF are independent of the US
government. They should not be construed as an official position of AHRQ or the
US Department of Health and Human Services.

Additional Information: The US Preventive Services Task Force (USPSTF) makes
recommendations about the effectiveness of specific preventive care services for
patients without obvious related signs or symptoms. It bases its recommendations
on the evidence of both the benefits and harms of the service and an assessment
of the balance. The USPSTF does not consider the costs of providing a service in
this assessment. The USPSTF recognizes that clinical decisions involve more
considerations than evidence alone. Clinicians should understand the evidence
but individualize decision-making to the specific patient or situation.
Similarly, the USPSTF notes that policy and coverage decisions involve
considerations in addition to the evidence of clinical benefits and harms.
Similarly, the USPSTF notes that policy and coverage decisions involve
considerations in addition to the evidence of clinical benefits and harms.
Published by JAMA®—Journal of the American Medical Association under arrangement
with the Agency for Healthcare Research and Quality (AHRQ). ©2022 AMA and United
States Government, as represented by the Secretary of the Department of Health
and Human Services (HHS), by assignment from the members of the United States
Preventive Services Task Force (USPSTF). All rights reserved.

Copyright Notice: USPSTF recommendations are based on a rigorous review of
existing peer-reviewed evidence and are intended to help primary care clinicians
and patients decide together whether a preventive service is right for a
patient's needs. To encourage widespread discussion, consideration, adoption,
and implementation of USPSTF recommendations, AHRQ permits members of the public
to reproduce, redistribute, publicly display, and incorporate USPSTF work into
other materials provided that it is reproduced without any changes to the work
of portions thereof, except as permitted as fair use under the US Copyright Act.

AHRQ and the US Department of Health and Human Services cannot endorse, or
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include a disclaimer to this effect. Advertising or implied endorsement for any
commercial products or services is strictly prohibited.

This work may not be reproduced, reprinted, or redistributed for a fee, nor may
the work be sold for profit or incorporated into a profit-making venture without
the express written permission of AHRQ. This work is subject to the restrictions
of Section 1140 of the Social Security Act, 42 U.S.C. §320b-10. When parts of a
recommendation statement are used or quoted, the USPSTF Web page should be cited
as the source.

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Table. Summary of USPSTF Rationale

Rationale Assessment Benefits of aspirin use Adequate evidence that low-dose
aspirin has a small benefit to reduce risk for cardiovascular events (nonfatal
myocardial infarction and stroke) in adults 40 years or older who have no
history of CVD but are at increased CVD risk. Evidence shows that the absolute
magnitude of benefit increases with increasing 10-year CVD risk and that the
magnitude of the lifetime benefits is greater when aspirin is initiated at a
younger age. Harms of aspirin use Adequate evidence that aspirin use in adults
increases the risk for gastrointestinal bleeding, intracranial bleeding, and
hemorrhagic stroke. The USPSTF determined that the magnitude of the harms is
small overall but increases in older age groups, particularly in adults older
than 60 years. USPSTF assessment

The USPSTF concludes with moderate certainty that aspirin use for the primary
prevention of CVD events in adults aged 40 to 59 years who have a 10% or greater
10-year CVD risk has a small net benefit. The USPSTF concludes with moderate
certainty that initiating aspirin use for the primary prevention of CVD events
in adults 60 years or older has no net benefit.

Abbreviations: CVD, cardiovascular disease; USPSTF, US Preventive Services Task
Force

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Figure. Quality-Adjusted Life-Years and Life-Years Gained: Lifetime Net Benefit
of Initiating Aspirin Use for Women and Men With Lifetime Use

Yellow shaded cells indicate persons to whom the C grade recommendation applies.
CVD indicates cardiovascular disease;
QALY, quality-adjusted life-year.

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