New draft recommendations from the US Preventive Services Task Force (USPSTF) on the use of aspirin for the primary prevention of cardiovascular disease (CVD) have been released and appear to limit the population in which it should be considered.
“The USPSTF concludes with moderate certainty that aspirin use for the primary prevention of CVD events in adults ages 40 to 59 years who have a 10% or greater 10-year CVD risk has a small net benefit,” the recommendation notes. They conclude that for these patients, the decision to use aspirin “should be an individual one.”
“Persons who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit,” they note.
For older individuals, however, “The USPSTF concludes with moderate certainty that initiating aspirin use for the primary prevention of CVD events in adults age 60 years or older has no net benefit,” the task force concludes.
The new recommendations were posted online today and will be available for public comment until November 8. Once it is finalized, the recommendation will replace the 2016 USPSTF recommendation on aspirin use to prevent CVD and colorectal cancer (CRC), they note.
In that document, the task force recommended initiating low-dose aspirin for the primary prevention of both CVD and CRC in adults 50-59 years of age who had a 10% or greater 10-year CVD risk, were not at increased risk for bleeding, had a life expectancy of at least 10 years, and were willing to take daily low-dose aspirin for at least 10 years, with the decision to start being an individual one.
For older and younger patients, they found at that time 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 age 50 years or adults aged 70 years or older.”
In the new draft document, “the USPSTF has changed the age ranges and grades of its recommendation on aspirin use.” Besides the recommendations for CVD prevention, they have also changed the previous recommendation of aspirin for the prevention of CRC given evidence generated from large primary CVD prevention trials.
“Based on new analyses of the evidence from primary CVD prevention populations, longer-term follow-up data from the Women’s Health Study (WHS) (JE Buring, personal communication, November 23, 2020), and new trial evidence, the USPSTF concluded that the evidence is inadequate that low-dose aspirin use reduces CRC incidence or mortality,” it states.
On the optimum dose for primary CVD prevention, the task force says the benefit appears similar for a low dose (≤100 mg/d) and all doses that have been studied in CVD prevention trials (50 to 500 mg/d). “A pragmatic approach would be to use 81 mg/d, which is the most commonly prescribed dose in the United States,” it states.
The USPSTF recommends using the ACC/AHA Pooled Cohort Equations to estimate cardiovascular risk but it points out that these equations are imperfect for risk prediction at the individual level, and 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), they note.
“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 than the potential harms may choose to initiate low-dose aspirin use. Persons who place a higher value on the potential harms or on the burden of taking a daily preventive medication than the potential benefits may choose not to initiate low-dose aspirin use,” the task force says.
It also points out that the risk for bleeding increases modestly with advancing age. “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, become smaller with advancing age because of an increased risk for bleeding, so modeling data suggest that it may be reasonable to consider stopping aspirin use around age 75 years,” it states.
The updated draft recommendations are based on a new systematic review commissioned by the USPSTF 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.
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.
The USPSTF found 13 randomized clinical trials (RCTs) that reported on the benefits of aspirin use for the primary prevention of cardiovascular morbidity and mortality. The total number of participants was 161,680, and most trials used low-dose aspirin of 100 mg/d or less or aspirin every other day. The 13 primary prevention trials included a balanced number of male and female participants and included a broad distribution of ages, with mean age ranging from 53 years in the Physicians’ Health Study to 74 years in the ASPREE trial.
This body of evidence shows that aspirin use for primary prevention of CVD is associated with a decreased risk of myocardial infarction and stroke but not cardiovascular mortality or all-cause mortality. Results are quite similar when including studies using all doses of aspirin compared with studies using low-dose aspirin.
The USPSTF reviewed 14 RCTs in CVD primary prevention populations that reported on the bleeding harms of aspirin.
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 showed that aspirin use was associated with a 58% increase in major gastrointestinal bleeding, and a pooled analysis of 11 trials showed a 31% increase in intracranial bleeds in the aspirin group compared with the control group. Low-dose aspirin use was not associated with a statistically significant increase in risk of fatal hemorrhagic stroke.
Data suggested that the increased risk 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. Although the increase in relative risk does not appear to differ based on age, the absolute risk of bleeding, and thus the magnitude of bleeding harm, does increase with age, and more so in adults age 60 years or older, they note.
The microsimulation model to estimate the magnitude of net benefit of low-dose aspirin use incorporated findings from the systematic review.
Modeling data demonstrated that aspirin use in both men and women ages 40-59 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 ages 60-69 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 ages 70-79 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).
The USPSTF thus determined that aspirin use has a small net benefit in persons ages 40-59 years with 10% or greater 10-year CVD risk, and initiation of aspirin use has no net benefit in persons age 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 suggest that there is generally little incremental lifetime net benefit in continuing aspirin use beyond the age of 75-80 years.
The task force points out that the net benefit of continuing aspirin use by a person in their 60s or 70s is not the same as the net benefit of initiating aspirin use by a person in their 60s or 70s. This is because, in part, of the fact that 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 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 a person at lower risk might gain by initiating aspirin use, the USPSTF explains.
USPSTF Draft Recommendation Statement. Published online October 12, 2021.
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