Grade: I The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.
The current evidence is 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.
Frequency of Service
No information available.
Risk Factor Information
No information available.
This recommendation applies to adults aged 40 years or older without known CVD (including history of MI or stroke) and without increased bleeding risk (for example, history of GI ulcers, recent bleeding, or use of medications that increase bleeding risk).
Assessment of the Balance of Benefits and Harms
The magnitude of the health benefits of aspirin use depends on an individual’s baseline CVD risk and willingness to take aspirin for a sufficient duration to obtain the benefit of reduced incidence of CRC. The magnitude of harms depends on the presence of risk factors for bleeding.
Baseline CVD Risk
The magnitude of the cardiovascular risk reduction with aspirin use depends on an individual’s initial risk for CVD events. Risk assessment for CVD should include ascertainment of the following risk factors: age, sex, race/ethnicity, total cholesterol level, high-density lipoprotein cholesterol level, systolic blood pressure, hypertension treatment, diabetes, and smoking. An online version of the ACC/AHA risk calculator can be found at http://tools.acc.org/ASCVD-Risk-Estimator/.
Colorectal cancer prevention plays an important role in the overall health benefit of aspirin, but this benefit is not apparent until 10 years after aspirin therapy is started. Patients need to take aspirin for at least 5 to 10 years to realize this potential benefit,6, 7 and persons with shorter life expectancy are less likely to benefit. Thus, aspirin use is more likely to have an effect when it is started between the ages of 50 and 59 years. Because of the time required before a reduced incidence in CRC is seen, older persons (that is, 60 years or older) are less likely to realize this benefit than adults aged 50 to 59 years.8
GI and Intracranial Bleeding
Evidence shows that risk for GI bleeding, with and without aspirin use, increases with age. For this recommendation, the USPSTF considered older age and male sex to be important risk factors for GI bleeding. Other risk factors include upper GI tract pain, GI ulcers, concurrent anticoagulation or NSAID use, and uncontrolled hypertension.4, 5 Nonsteroidal anti-inflammatory drug therapy combined with aspirin use increases the risk for serious GI bleeding compared with aspirin use alone.9 The rate of serious bleeding among aspirin users is about 2 to 3 times greater in patients with a history of GI ulcer.10 The risk for serious GI bleeding is 2 times greater in men than in women.10 These risk factors increase the risk for bleeding substantially and should be considered in the overall decision about whether to start or continue aspirin therapy. There is no evidence that enteric-coated or buffered formulations reduce the risk for serious GI bleeding.2, 4, 11
Balance of Benefits and Harms
The USPSTF used a CVD microsimulation model to estimate cardiovascular event rates based on baseline risk factors and aspirin use. It used the AHA/ACC risk calculator to stratify findings of benefits and harms by 10-year CVD risk. The USPSTF also calculated estimates of CRC incidence and harms of bleeding to determine the net balance of benefits and harms across individuals with varying baseline CVD risk.8, 12
Table 1 and Table 2 present the USPSTF’s estimated lifetime number of nonfatal MIs, ischemic strokes, and cases of CRC prevented, stratified by 10-year CVD risk level, age, and sex, among adults aged 50 to 69 years (the age range with evidence of net benefit from aspirin use). In addition, Table 1 and Table 2 present the USPSTF’s estimated lifetime number of GI bleeding events and hemorrhagic strokes. The USPSTF developed these estimates assuming that aspirin users are not taking NSAIDs and do not have other conditions that increase risk for GI bleeding. The USPSTF estimated life-years and quality-adjusted life-years (QALYs) saved as one part of its consideration of the balance of benefits and harms of these disparate clinical outcomes (see the Implementation section for more information on interpreting the results in Table 1 and Table 2).
Overall, the USPSTF determined that the greatest net benefit to be gained is by adults aged 50 to 59 years whose 10-year CVD risk is 10% or greater. The USPSTF recommends that persons in this age and risk group start taking aspirin. Adults aged 60 to 69 years may also benefit from starting aspirin use, although the net benefit is smaller due to the increased risk for GI bleeding and decreased benefit in CRC prevention in this age group.8
Further, the decision about the level of CVD risk at which the potential benefits outweigh potential harms is an individual one. Some adults may decide that avoiding an MI or a stroke is very important and that having a GI bleeding event is not as significant. They may decide to take aspirin at a lower CVD risk level than those who are more concerned about GI bleeding. Adults who have a high likelihood of benefit with little potential for harm should be encouraged to consider aspirin use. Conversely, adults who have little potential for benefit or are at high risk for GI bleeding should be discouraged from it.
Treatment and Dosage
The optimal dose of aspirin to prevent CVD events is not known. Primary prevention trials have demonstrated benefits with various regimens, including doses of 75 and 100 mg per day and 100 and 325 mg every other day. A dose of 75 mg per day seems as effective as higher doses. The risk for GI bleeding may increase with the dosage. A pragmatic approach consistent with the evidence is to prescribe 81 mg per day, which is the most commonly prescribed dose in the United States.
Although the optimal timing and frequency of discussions about aspirin therapy are unknown, a reasonable approach may be to assess CVD and bleeding risk factors starting at age 50 years and periodically thereafter, as well as when CVD and bleeding risk factors are first detected or change.
Suggestions for Practice Regarding the I Statements
Potential Preventable Burden
Evidence from primary prevention trials on the benefits of initiating aspirin use in adults younger than 50 years is limited. The potential benefit is probably lower than in adults aged 50 to 69 years because the risk for CVD events is lower (only a small percentage of adults younger than 50 years have a 10-year CVD risk ≥10%).8 Adults younger than 50 years who have an increased 10-year CVD risk may gain significant benefit from aspirin use; how much benefit is uncertain.
Evidence on the benefits and harms of initiating aspirin use in older adults is limited. Many adults aged 70 years or older are at increased risk for CVD because of their age. They have a high incidence of MI and stroke; thus, the potential benefit of aspirin could be substantial.
The relationship between older age and GI bleeding is well-established; thus, the potential harms for adults older than 70 years are significant. The complexity of risk factors, medication use, and concomitant illness make it difficult to assess the balance of benefits and harms of initiating aspirin use in this age group. In addition, aspirin use in adults older than 70 years results in smaller reductions in the incidence of CRC compared with younger adults.
Nearly 40% of U.S. adults older than 50 years use aspirin for the primary or secondary prevention of CVD.5 A study of National Health and Nutrition Examination Survey data assessed how common aspirin use is for the primary prevention of CVD and whether physicians recommend it or patients start it on their own. Among patients who were eligible for aspirin therapy and were at increased CHD risk (>10% 10-year risk), about 41% were told by a physician to take aspirin. Among patients aged 65 years or older who were told by a physician to take aspirin, 80% adhered to the recommendation.13
The USPSTF has made other recommendations on CVD prevention, including smoking cessation and promoting a healthful diet and physical activity, as well as screening for carotid artery stenosis, CHD, high blood pressure, lipid disorders, obesity, diabetes, and peripheral artery disease. In addition, it has made recommendations on screening for CRC. These recommendations are available on the USPSTF Web site (www.uspreventiveservicestaskforce.org).
Additional Approaches to Prevention
Million Hearts (www.millionhearts.hhs.gov) is a national initiative to prevent 1 million heart attacks and strokes by 2017. It aims to prevent heart disease and stroke by improving access to effective care, improving the quality of care for the “ABCS” (aspirin when appropriate, blood pressure control, cholesterol management, and smoking cessation), focusing clinical attention on the prevention of heart attack and stroke, and activating the public to lead a heart-healthy lifestyle.
The Community Preventive Services Task Force recommends several intervention strategies to prevent CVD for communities and health care organizations (available at www.thecommunityguide.org/cvd/). For health care systems, it recommends introducing clinical decision-support systems to implement clinical guidelines at the point of care. For insurers and payers, it recommends reducing out-of-pocket costs to patients for medications to control high blood pressure and high cholesterol. For clinicians and health care organizations, it recommends incorporating multidisciplinary team-based care to improve blood pressure control, including patients, primary care providers, and other professionals (such as nurses, pharmacists, dietitians, social workers, and community health workers).
The decision to start or continue taking aspirin to prevent CVD and CRC is complex, with many important factors for clinicians and patients to consider. The most favorable balance of benefits and harms involves benefit for both CVD and CRC prevention and little potential for harm from bleeding. Persons who either are at low risk for CVD events or have a life expectancy too short to benefit from a reduced risk for CRC will receive significantly less benefit; thus, the balance of benefits and harms will likely not be favorable.
The balance of benefits and harms of aspirin use is contingent on 4 main factors: risk for bleeding, preferences about taking aspirin, baseline CVD risk, and age.
- Risk for bleeding: Aspirin use is likely to do more harm than good in persons who are at increased risk for GI or intracranial bleeding.
- Preferences about taking aspirin: Persons who place a high value on avoiding long-term daily medication use are poor candidates for aspirin use.
- Baseline CVD risk: A CVD risk threshold of 10% should prompt a discussion about aspirin use. Persons who are at higher risk will benefit more from aspirin use than those who are near the 10% threshold. Although persons who are at lower risk may still receive benefit, they are less likely to have a favorable balance of benefits and harms.
- Age 50 to 59 years: Initiating aspirin in this age group has the largest average net benefit (Table 1 and Table 2). A CVD risk threshold of 10% will identify patients for whom the benefits outweigh the harms, provided they are not at increased risk for bleeding and are willing to take long-term daily medication. In addition, persons in this age range generally have sufficient life expectancy to benefit from a reduced risk for CRC.
- Age 60 to 69 years: Adults in this age group with a higher CVD risk are most likely to have a favorable balance of benefits and harms, and younger adults are more likely to benefit from a reduced risk for CRC. Adults aged 60 to 69 years who are already taking aspirin as recommended by their clinician should continue use unless they develop new risk factors for bleeding. Adults who develop CVD should use aspirin, as directed by their clinician, to prevent future CVD events.
- Age 70 years or older: The USPSTF was unable to assess the balance of benefits and harms of initiating aspirin use in this age group. Adults aged 70 years or older who are currently taking aspirin should discuss with their clinician whether they should continue.
The time to benefit for CRC (that is, reduced CRC incidence and death) and time to harm are important considerations in assessing the benefits and harms of initiating aspirin use in older adults. The CVD prevention benefit begins within the first 5 years of use and continues as long as aspirin is used. The CRC prevention benefit is more complex. It takes at least 5 to 10 years of daily aspirin use to obtain a CRC benefit; however, due to a longer latent period, the benefit may take 10 to 20 years to appear. Therefore, older adults and those with shorter remaining life expectancy may receive less benefit. Meanwhile, bleeding harms may occur in the short term.
Table 1 and Table 2 provide information to help clinicians understand the balance of benefits and harms of aspirin therapy, especially for adults in their 60s. The magnitude of net benefit is smaller at lower 10-year CVD risk levels and greater at higher levels. For both men and women, CRC benefits tend to be lower at higher CVD risk levels due to competing causes of mortality, including death from CVD.
Research Needs and Gaps
There are many important research gaps that, if filled, could identify populations that may benefit the most from using aspirin to prevent CVD and CRC. Cardiovascular disease prevention in subpopulations is a significant evidence gap. No data exist on the role of aspirin therapy in racial/ethnic groups. Additional evidence on benefits and harms in persons younger than 50 years or 70 years or older would help clarify who could potentially benefit from aspirin use. An updated version of the individual-patient data meta-analysis from the Antithrombotic Trialists’ Collaboration that accounts for confounders would be helpful in understanding the effect of aspirin in subpopulations.
More information is needed to determine the interactions between statins and aspirin. How the use of proton-pump inhibitors with aspirin may change the balance of benefits and harms should be better understood. In addition, more information is needed to differentiate between aspirin’s effect in reducing risk for ischemic stroke and increasing risk for hemorrhagic stroke.
The effect of aspirin use on CRC prevention in subpopulations is also an important research gap. The differential effects of sex, race/ethnicity, age, and genetic factors on risk for CRC and the effect of screening require additional research. More research is also needed to determine the best dosing strategies, the long-term effects in persons with previous adenoma and on adenoma prevention, and the durability of benefits after aspirin is discontinued. Longer-term follow-up of CVD prevention trials that report cancer incidence and mortality outcomes would be helpful.
Additional research is needed to better estimate the harms of aspirin-induced GI bleeding. Development of an externally validated risk assessment tool for bleeding that could be used at the point of care would be helpful. A tool that considers both CVD risk and GI bleeding risk would be useful to clinicians and patients when deciding whether to start or continue aspirin use for primary prevention.
Update of Previous USPSTF Recommendation
This recommendation updates the 2009 USPSTF recommendation on aspirin use to prevent CVD events and the 2007 recommendation on aspirin and NSAID use to prevent CRC. To update these recommendations, the USPSTF reviewed 5 additional studies of aspirin for the primary prevention of CVD and several additional analyses of CRC follow-up data. The USPSTF also relied on reviews of all-cause mortality and total cancer incidence and mortality and a comprehensive review of harms. The USPSTF then used a microsimulation model to systematically estimate the balance of benefits and harms.
Cardiovascular disease and CRC are major causes of death among U.S. adults. In 2011, more than one half of all deaths in the United States were caused by heart disease, cancer, or stroke.1, 2
Recognition of Risk Status
The primary risk factors for CVD include older age, male sex, race/ethnicity, abnormal lipid levels, high blood pressure, diabetes, and smoking.2
The USPSTF used a calculator derived from the American College of Cardiology/American Heart Association (ACC/AHA) pooled cohort equations to predict 10-year risk for first hard atherosclerotic CVD event (defined as nonfatal myocardial infarction [MI], coronary heart disease [CHD] death, and fatal or nonfatal stroke).3 Although concerns have been raised about the equations’ potential to overpredict risk and their moderate discrimination, they are the only U.S.-based, externally validated equations that report risk as a combination of cerebrovascular and CHD events.
Risk factors for gastrointestinal (GI) bleeding with aspirin use include higher dose and longer duration of use, history of GI ulcers or upper GI pain, bleeding disorders, renal failure, severe liver disease, and thrombocytopenia. Other factors that increase risk for GI or intracranial bleeding with low-dose aspirin use include concurrent anticoagulation or nonsteroidal anti-inflammatory drug (NSAID) use, uncontrolled hypertension, male sex, and older age.4, 5
This recommendation applies to adults who are at increased CVD risk and at average risk for CRC. Persons who are at increased CVD risk and are known to be at increased risk for CRC (for example, persons with a family or personal history of CRC or familial adenomatous polyposis)6 should consult their health care provider.
Benefits of Aspirin Use
The USPSTF found adequate evidence that aspirin use to reduce risk for cardiovascular events (nonfatal MI and stroke) in adults aged 50 to 69 years who are at increased CVD risk is of moderate benefit. The magnitude of benefit varies by age and 10-year CVD risk.
The USPSTF found adequate evidence that aspirin use reduces the incidence of CRC in adults after 5 to 10 years of use.
The USPSTF found inadequate evidence that aspirin use reduces risk for CVD events in adults who are at increased CVD risk and are younger than 50 years or older than 69 years.
Harms of Aspirin Use
The USPSTF found adequate evidence that aspirin use in adults increases the risk for GI bleeding and hemorrhagic stroke. The USPSTF determined that the harms vary but are small in adults aged 59 years or younger and small to moderate in adults aged 60 to 69 years. The USPSTF found inadequate evidence to determine the harms of aspirin use in adults aged 70 years or older.
In adults aged 50 to 69 years who are at increased CVD risk, the benefits of aspirin use include prevention of MI and ischemic stroke and, with long-term use, reduced incidence of CRC. Aspirin use may also result in small to moderate harms, including GI bleeding and hemorrhagic stroke.
The USPSTF concludes with moderate certainty that the benefit of aspirin use for the primary prevention of CVD events, combined with the reduced incidence of CRC, outweighs the increased risk for bleeding by a moderate amount in adults aged 50 to 59 years who have a 10-year CVD risk of 10% or greater.
The USPSTF concludes with moderate certainty that the benefit of aspirin use for the primary prevention of CVD events, combined with the reduced incidence of CRC, outweighs the increased risk for bleeding by a small amount in adults aged 60 to 69 years who have a 10-year CVD risk of 10% or greater.
The USPSTF concludes that the evidence on aspirin use in adults younger than 50 years or older than 69 years is insufficient and the balance of benefits and harms cannot be determined.
Recommendations of OthersThe AHA and the American Stroke Association34 recommend the use of low-dose aspirin for cardiovascular (including but not specific to stroke) prophylaxis in adults whose risk is sufficiently high for the benefits to outweigh the risks associated with treatment; they suggest that a 10-year CVD risk of 6% to 10% is sufficient. The American Diabetes Association suggests low-dose aspirin therapy for primary prevention in patients with type 1 or 2 diabetes who have an increased CVD risk (>10% 10-year CVD risk) and are not at increased risk for bleeding. It does not recommend aspirin therapy in men younger than 50 years or most women younger than 60 years who have low CVD risk because the risk for bleeding outweighs the potential benefits of aspirin treatment.35 Previous recommendations from the American Academy of Family Physicians about aspirin use for the primary prevention of CVD and CRC have been consistent with those of the USPSTF.36 The American College of Chest Physicians suggests that patients older than 50 years without symptomatic CVD use low-dose aspirin for primary CVD prevention.37 No organizations recommend aspirin use for the primary prevention of CRC in average-risk adults. The American Cancer Society recognizes that long-term regular aspirin use has both harms and benefits, including reduced risk for CRC, but has not formally reviewed the evidence and does not currently have recommendations for or against aspirin use. The American Gastroenterological Association and the National Comprehensive Care Network limit their recommendations to patients who are at increased risk for CRC.6 The U.S. Food and Drug Administration recently denied a manufacturer’s request to add primary prevention of MI as an indication for aspirin use in any risk group. In a consumer bulletin, it noted the risks for GI and intracranial bleeding and suggested that the benefits of primary prevention have not been well-established.38
- Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: Consumer Guide
- Aspirin to Prevent Cardiovascular Disease and Colorectal Cancer: AFP's Putting Prevention Into PracticeThe journal American Family Physician (AFP) provides a series of short case studies and quizzes based on recommendations issued by the U.S. Preventive Services Task Force.