Based on a review of the evidence, the task force said whether to initiate low-dose aspirin use for the primary prevention of CVD in adults ages 40 to 59 years with a 10% or greater 10-year CVD risk should be an individual decision. The task force also said current evidence indicates that the net benefit of aspirin use in this population is small, and that the people most likely to benefit are those who are not at increased risk for bleeding and are willing to take low-dose aspirin on a daily basis. This is a “C” recommendation.
The task force also recommended against initiating low-dose aspirin use for CVD prevention in adults 60 years or older; this is a “D” recommendation.
The recommendations apply to adults 40 years or older who do not have signs or symptoms of CVD or known CVD who are not at increased risk for bleeding.
“People who are 40 to 59 years old and who don’t have a history of CVD but are at higher risk may benefit from starting to take aspirin to prevent a first heart attack or stroke,” said task force member John Wong, M.D., in a USPSTF bulletin. “It’s important that they decide together with their health care professional if starting aspirin is right for them because daily aspirin use does come with possible serious harms.”
The task force stressed that the recommendations do not apply to those who already have heart disease, have experienced a stroke or are taking aspirin. These individuals are encouraged to speak with a health care professional about their situation.
“We want to emphasize that these recommendations are focused on starting aspirin to prevent a first heart attack or stroke,” Wong added. “Anyone who already takes aspirin and has questions about it should speak with their health care professional.”
According to the CDC, cardiovascular disease is the leading cause of death and disability worldwide. In the United States, CVD is responsible for more than 877,000 deaths annually, a figure roughly equal to the combined number of deaths caused by accidents, cancer and lower respiratory diseases. CVD also has a significant economic impact, resulting in an estimated $216 billion in health care system costs and $147 billion in lost productivity due to premature death each year.
The final recommendation replaces and markedly differs from the task force’s previous 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.
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 group 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.
In addition, the task force concluded that the evidence available at the time 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 70 and older.
The AAFP supported the 2016 recommendation.
To update the existing recommendation, the USPSTF commissioned a systematic review of the evidence 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 examined the effects of aspirin use on colorectal cancer incidence and mortality in primary CVD prevention populations, and the harms associated with aspirin use. In addition, the task force 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 on the Medline and PubMed databases and the Cochrane Collaboration Registry of Controlled Trials between January 2014 and Jan. 14, 2021. The literature search was supplemented with reference lists from the previous evidence review, relevant existing systematic reviews, suggestions from experts, and citations from Clinicaltrials.gov to identify ongoing trials. Ongoing surveillance was conducted through Jan. 21, 2022. A total of 23 studies were included in the review, including six newly identified trials and cohorts.
Although the task force defined low-dose aspirin use as 100 mg or less per day, and noted that CVD prevention trials have used aspirin dosages ranging from 50 to 500 mg per day, it stated that “a pragmatic approach” would be 81 mg per day, which is the dose most commonly prescribed in the United States.
A pooled analysis of 11 trials involving 134,470 participants showed that low-dose aspirin use was associated with a statistically significant decreased risk of nonfatal myocardial infarction.
A similar pooled analysis of five trials involving 54,947 participants showed that low-dose aspirin use was associated with a statistically significant decreased risk of nonfatal ischemic stroke.
Because fatal cardiovascular events were less common, pooled analyses that followed patients for between 3.6 years and 10.1 years 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.
While evidence did not suggest that the relative effect of aspirin on CVD outcomes is modified by baseline CVD risk, the task force stated that the absolute magnitude of the benefit of effect is greater in those at higher CVD risk.
Evidence on the effects of aspirin use on cardiovascular cancer incidence and mortality was limited, although results from one trial indicated an increased risk of colorectal cancer mortality in older adults.
With regard to harms, a pooled analysis of 10 trials involving 119,130 participants found that aspirin use was associated with a 58% increase in major gastrointestinal bleeding. Another pooled analysis of 11 trials involving 134,470 participants showed a 31% increase in intracranial bleeds in patients who took aspirin compared with controls.
According to the task force, trial data suggested that the increased incidence of bleeding associated with aspirin use occurs relatively quickly after initiating aspirin, but do not suggest that aspirin has a differential relative bleeding risk based on age, sex, presence of diabetes, level of CVD risk, race or ethnicity.
Data from the modeling study, meanwhile, indicated that aspirin use in both men and women ages 40 to 50 years with a 10% or greater 10-year CVD risk generally provides a modest net benefit in quality-adjusted life-years and life-years gained. In people ages 60 to 69, aspirin use provided slightly negative to slightly positive results based on CVD risk level, while 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.
When examining the net lifetime benefit of continuous aspirin use until stopping at age 65, 70, 75, 80 or 85 years, the modeling data also suggested that there is generally little incremental lifetime net benefit in continuing aspirin use beyond the range of 75 to 80 years.
A draft version of the recommendation statement was posted on the USPSTF website for public comment from Oct. 12, 2021, to Nov. 8, 2021.
In response to numerous comments, the task force emphasized that the focus of the recommendation is the use of aspirin for the primary prevention of CVD, not other indications. The task force also reiterated that the recommendation only applies to people who do not have a history of CVD, signs or symptoms of CVD, or other conditions for which aspirins may be indicated. People who are currently taking aspirin and have questions about why they are taking it and whether to continue or discontinue aspirin use are strongly encouraged to discuss these questions with their clinician; people currently taking aspirin should not discontinue use without first consulting their clinician.
In response to comments on risk assessment, the task force clarified language about its assessment of the precision of CVD risk assessment and added information on factors clinicians and patients can consider as they participate in shared decision-making on the initiation of aspirin use.
The task force also noted that it did not review any of the emerging evidence on the effects of aspirin use on COVID-19.
Lynn Fisher, M.D., an assistant professor in the Department of Family and Community Medicine at the University of Kansas School of Medicine-Wichita and a member of the Academy’s Commission on Health of the Public and Science, explained the significance of the recommendation to AAFP News.
“I think this recommendation is important because many of us have patients who are taking a baby aspirin daily without a prior history of heart attack or stroke, and sometimes patients will do this on their own without talking to their doctor first,” said Fisher. “Since aspirin is available over the counter, many patients may feel that this is a safe medication to take.
“For years, the message from doctors was to take a baby aspirin daily to help prevent a heart attack and stroke, especially if (the patient was) at increased risk,” Fisher added. “Now we know that the majority of patients who have not had a stroke or heart attack should not be taking a daily baby aspirin due to increased risks from bleeding.”
Fisher also stated that FPs should stress the importance of other approaches to CVD prevention.
“It is now obvious that aspirin should not play a prominent role for prevention of CVD. Family physicians should emphasize more lifestyle interventions, such as healthy eating and increased physical activity to prevent the onset of hypertension and diabetes. We will also need to continue to address risk factors such as blood pressure, diabetes, hypercholesterolemia and smoking.”
When discussing CVD risks, Fisher said he uses 10-year risk percentage calculators to help patients understand the role that factors such as smoking or uncontrolled blood pressure can play in elevating that risk compared with patients who do not smoke or whose blood pressure is normal.
“My hope is that sometimes that can be motivating to a patient to stop smoking or to work on lifestyle interventions to lower blood pressure,” Fisher said. “Often patients would rather do these things versus take an additional medication such as a statin to lower the risk.”
Finally, Fisher reminded family physicians to remember that recommendations can change over time.
“If we have better data, then we should be willing to change our advice,” said Fisher. “It is important for patients to know that at this time, this is the best evidence-based recommendation that we can make, and that in the future if that data suggests something different, our recommendation could change again.”
The Commission on Health of the Public and Science will review the task force’s final recommendation statement, final evidence review, final modeling report, evidence summary and modeling study, and will then determine the Academy’s stance on the recommendation.