Based on its review of the evidence, the task force has concluded 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 produces a small net benefit, that the decision to initiate low-dose aspirin use for the primary prevention of CVD in this patient population should be an individual one, and that people who are not at increased risk for bleeding and who are willing to take low-dose aspirin daily are more likely to benefit. This is a “C” recommendation, and applies to adults 40 to 59 years without known CVD (including a history of stroke or myocardial infarction) who are not at increased risk for bleeding.
The task force has also concluded with moderate certainty that initiating aspirin use for the primary prevention of CVD in adults 60 years or older has no net benefit, and recommends against the initiation of aspirin use for the primary prevention of CVD in this population — a “D” recommendation.
“The risks of low-dose aspirin for primary prevention of cardiovascular disease in adults age 60 years and older outweigh the benefits and should not be used in this population,” Sarah Coles, M.D., chair of the AAFP’s Commission on Health of the Public and Science and an assistant professor in the Department of Family, Community and Preventive Medicine at the University of Arizona College of Medicine – Phoenix Family Medicine Residency, told AAFP News. “Family physicians should have a discussion with individuals aged 40 to 59 with elevated atherosclerotic CVD risk about both the risks and benefits of low-dose aspirin for primary prevention.”
Cardiovascular disease is the leading cause of death and disability worldwide. According to HHS’ Million Hearts initiative, one-third of all deaths in the United States each year are caused by CVD. Overall, the initiative estimates that more than 800,000 people in the United States die from heart disease each year, a figure roughly equal to the number of deaths from cancer, lower respiratory diseases and accidents combined.
The new draft recommendation differs substantially with regard to the age ranges and grades from the task force’s existing recommendation statement on the topic, which was published in April 2016.
In the 2016 statement, the USPSTF recommended initiating low-dose aspirin for the primary prevention of CVD and colorectal cancer in adults ages 50 to 59 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 low-dose aspirin daily for at least 10 years (a “B” recommendation).
The task force also stated that the decision to initiate low-dose aspirin use for the primary prevention of CVD and colorectal cancer in adults ages 60 to 69 with a 10% or greater 10-year CVD risk should be an individual one; that individuals in this patient population who were not at increased risk for bleeding, had a life expectancy of at least 10 years and were willing to take low-dose aspirin daily for at least 10 years were more likely to benefit; and that people who placed a higher value on the potential benefits than the potential harms might choose to initiate low-dose aspirin (a “C” recommendation).
In addition, the task force concluded at the time that the available evidence was insufficient to balance the benefits and harms of initiating aspirin use for the primary prevention of CVD and colorectal cancer in adults younger than 50 or in those 70 and older.
The AAFP supported the 2016 recommendation.
To update the existing recommendation, the task force commissioned a systematic evidence review on the effectiveness of aspirin to reduce the risk of CVD events, cardiovascular mortality and all-cause mortality in people without a history of CVD. The review also investigated the effect of aspirin use on colorectal cancer incidence and mortality in primary CVD prevention populations, as well as the harms of increased bleeding risk associated with aspirin use.
For the new draft recommendation, the USPSTF also commissioned a modeling study to assess the net balance of benefits and harms from aspirin use for the primary prevention of CVD and colorectal cancer, with the results stratified by age, sex and CVD risk level.
The review consisted of studies published between January 2014 and Jan. 14, 2021, with searches supplemented via reference lists from the previous systematic reviews, relevant existing systematic reviews, expert suggestions and Clinicaltrials.gov. A total of 23 studies were included in the review, including three new trials and three new cohort studies.
While the task force defined low-dose aspirin use as 100 mg or less per day and noted that dosages studied in CVD prevention trials ranged from 50 to 500 mg per day, it stated that “a pragmatic approach” would be to use 81 mg per day, which is the dose most commonly prescribed in the United States.
Pooled analyses showed that low-dose aspirin use was associated with statistically significant decreased risks for nonfatal myocardial infarction and nonfatal ischemic stroke, but not for fatal myocardial infarction, fatal stroke, cardiovascular mortality or all-cause mortality. In addition, while the evidence did not suggest that the relative effect of aspirin on CVD outcomes was modified by baseline CVD risk, the absolute magnitude of the benefit was higher in individuals at increased CVD risk.
Evidence on the effects of aspirin use on colorectal cancer incidence and mortality was limited. Only a small number of trials reported on colorectal cancer outcomes, and results from four studies conducted in primary CVD prevention populations found no association between aspirin use and colorectal cancer incidence at up to approximately 10 years of followup.
In studies that reported on the harms of low-dose aspirin use, one pooled analysis showed that aspirin use was associated with a 58% increase in major gastrointestinal bleeding, while another pooled analysis indicated an increase in intracranial bleeding in patients who took aspirin compared with a control group.
Data from the modeling study, meanwhile, indicated that while aspirin use produced a small net benefit in people ages 40 to 59 with a 10% or greater 10-year CVD risk, initiation of aspirin had no net benefit in those ages 60 or older. Moreover, in individuals ages 70 to 79, initiation of aspirin use resulted in a loss of both quality-adjusted life years and life-years at virtually every CVD risk level modeled.
“The role of aspirin use in primary prevention for CVD will continue to evolve based on the closely matched magnitude of CVD benefit and bleeding risks in the context of declining smoking rates, increasing statin use and more aggressive hypertension management,” the task force concluded in the evidence review.
“The latest evidence is clear: Starting a daily aspirin regimen in people who are 60 or older to prevent a first heart attack or stroke is not recommended,” added Chien-Wen Tseng, M.D., M.P.H., M.S.E.E., a professor and research director in the Department of Family Medicine and Community Health at the University of Hawaii John A. Burns School of Medicine, in a press release. “However, this task force recommendation is not for people already taking aspirin for a previous heart attack or stroke; they should continue to do so unless told otherwise by their clinician.”
Coles told AAFP News that the revised age ranges and recommendation grades could substantially affect the way family physicians care for certain patient populations.
“This is a major change from how we were previously thinking about low-dose aspirin in primary prevention,” said Coles. “Family physicians will likely be deprescribing this medication for many folks, particularly for those aged 60 and above who are taking aspirin for primary prevention. I suspect many patients will have questions about this, because for some they have been on this medication for a long time and have long-held beliefs about safety and efficacy. Family physicians should be prepared to discuss the evidence of both benefit and harm.
“Of note, this draft recommendation also removed primary prevention of colorectal cancer as an indication for low-dose aspirin,” Coles added. “The evidence review did not find sufficient evidence that low-dose aspirin reduced colorectal cancer incidence or mortality. More research is needed in this area.”
Coles also expressed some concern over the task force’s recommendation to use the American College of Cardiology/American Heart Association pooled cohort equations to estimate 10-year CVD risk.
“This tool uses race as a variable in its equation without scientific justification or recognition of the structural, social and environmental factors that result in health disparities,” Coles explained. “The AAFP is opposed to the use of race as a proxy for biology or genetics in clinical evaluation. Race is a social construct, not a biological one, and use of race-based calculators in clinical decision-making can increase disparities.
“Using this calculator, family physicians may overestimate the ASCVD risk for individuals who identify as African American or Black,” Coles continued. “Family physicians need to recognize the limitation of this tool in estimating ASCVD risk and discuss this with their patients when helping to make prevention recommendations.”
All comments will be considered as the USPSTF prepares its final recommendation.