The USPSTF’s Updated Guidelines on Aspirin Use for the Primary Prevention of Cardiovascular Disease

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Updated: The United States Preventive Services Task Force’s Guidelines on Aspirin Use for the Primary Prevention of Cardiovascular Disease

Author: Christine Zink, MD

Please Note: The USPSTF guidelines have been finalized since we initially wrote this blog post. This post has been updated to reflect the final guidelines.

Aspirin is the most widely used drug in medicine, and its benefits have been well documented since the 1980s. Initially, the medicine was recommended for the primary and secondary prevention of cardiovascular disease in at-risk people. However, medical organizations like the United States Preventive Services Task Force (USPSTF) are updating their recommendations based on new data. Discover aspirin history, recall the initial recommendations for its use to prevent cardiovascular disease, and learn the newest recommendations by reading this article.

Key Points

  • If a person has had a heart attack, stroke, coronary stent, or coronary artery bypass grafting, they should be taking aspirin unless it is contraindicated for another reason. 
  • If a person has not had a cardiovascular event and is over age 60, under age 40, or at increased risk of bleeding, they should not take aspirin for the primary prevention of cardiovascular disease.
  • If a person is between ages 40 and 59, at low risk of bleeding, and thought to have at least 10% 10-year cardiovascular disease risk, they might benefit from daily aspirin therapy. This is a grade C recommendation.

The History of Aspirin Use

Aspirin is the most widely used drug in medicine.1 It has been around since the time of the Mesopotamian civilizations. However, public use for clinical reasons did not begin until 1904.1 Scientists by then had been observing the antithrombotic properties of aspirin, but the exact mechanism of action that led to these effects was not understood until 1971.1 We now know that aspirin irreversibly inhibits platelet function, which reduces a person’s risk of atherothrombosis. However, this also means that people are at risk for bleeding.2 

The benefit of aspirin for the primary prevention of cardiovascular disease has been well-established by research over the past 30 years.1 Early clinical trials were performed in a mix of healthy patients and people with cardiovascular disease risks, including atherosclerotic disease and diabetes.1 It was during this time that medical organizations started recommending daily aspirin because of its net benefits, while only a few questioned the possibility of increased bleeding events.

Since that time, an increasing number of people with and without cardiovascular disease risks have been taking aspirin daily. A paper using data from the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994, reported that 25% of people age 60 and older with diabetes used aspirin as a preventative medication over the prior 30 days before the survey was conducted.3 A telephone survey conducted from 1997 to 2001 found that 47% of people age 65 years and older without cardiovascular disease used aspirin.3 And, most recently, according to a 2017 National Health Interview Survey, nearly 30 million Americans age 40 and older and 40% of adults age 70 and older who did not have cardiovascular disease took an aspirin every day to protect their hearts.4 Among those, 6.6 million did it without a recommendation from their clinician.4 

Previous Recommendations for the Use of Aspirin to Prevent Cardiovascular Disease

Aspirin use for the secondary prevention of serious cardiovascular events is well accepted. Several trials have established the benefits of low-dose aspirin in people who have already had2:

  • Myocardial infarction
  • Stroke
  • Placement of a coronary artery stent
  • Coronary artery bypass graft surgery 

Initial studies also supported aspirin use for the primary prevention of cardiovascular disease in people at risk for cardiovascular events. However, in 2019, the American College of Cardiology and American Heart Association (ACC/AHA) updated their guidelines on the use of aspirin for the primary prevention of cardiovascular disease based on updated analyses.5 This created an alteration in guidelines from other medical organizations such as the United States Preventive Services Task Force.6 

Previously, the USPSTF recommended low-dose aspirin for primary prevention of cardiovascular disease and colorectal cancer in adults ages 50–59 years who had a 10% or greater 10-year cardiovascular disease risk, a life expectancy of at least 10 years, and no increased risk for bleeding.6 The task force indicated that in patients ages 60–69 years with a 10% or greater 10-year cardiovascular disease risk, the decision to initiate aspirin treatment should be based on individual factors.6 The task force also indicated that evidence was insufficient to balance the benefits and harms of initiating low-dose aspirin in people younger than 50 years or 70 years and older.6

The Basis for Changing the Recommendations

Three new recently published trials helped researchers address limitations in the initial data used to support aspirin use for the primary prevention of cardiovascular disease. These three trials—ARRIVE (Aspirin to Reduce Risks of Initial Vascular Events), ASCEND (A Study of Cardiovascular Events in Diabetes), and ASPREE (Aspirin in Reducing Events in the Elderly)—addressed three populations: people with cardiovascular disease risks, people with diabetes, and older adults.7 The combined meta-analysis of these new trials with 10 previous primary prevention trials included data from just over 164,000 participants.7 The new analysis demonstrated that aspirin reduced the risk of cardiovascular events by 11%.7 However, bleeding risk was increased by 43%.7 There was also a nonsignificant 6% reduction in mortality.7

Each new trial demonstrated different specific outcomes. In ARRIVE, there was no significant difference in cardiovascular outcomes in people with underlying cardiovascular disease risks.8 In ASCEND, there was a significant reduction in primary cardiovascular events in people with diabetes, but there were major bleeding events.9 In ASPREE, there were increased rates of bleeding in older adults without a significant difference in primary cardiovascular events.10

This new information has helped medical organizations adjust their recommendations and provides a basis for the updated USPSTF guidelines. The new recommendations generally rely on a clinician’s ability to accurately estimate a person’s cardiovascular disease risk and then use a personalized approach to decide on the utility of aspirin therapy. Several tools are available to estimate cardiovascular disease risk, but the ACC/AHA recommends their updated Atherosclerotic Cardiovascular Disease Risk Estimator Plus.11

The Newest Recommendations Regarding the Primary Prevention of Cardiovascular Disease

In the new recommendation, the USPSTF6:

  • Recommends that the decision to initiate low-dose aspirin for the primary prevention of cardiovascular disease in adults ages 40–59 years who have a 10% or greater 10-year cardiovascular disease risk be an individual decision.
  • Recommends against initiating low-dose aspirin for the primary prevention of cardiovascular disease in adults age 60 years and older.
  • Concludes that evidence is inadequate for using low-dose aspirin to reduce colorectal cancer incidence or mortality.

These updated guidelines apply to adults age 40 years and older without known cardiovascular disease and who are not at increased risk for bleeding.6 These guidelines do not apply to people who have already had a myocardial infarction or stroke. The daily use of aspirin is still recommended in these patients.

To make these new recommendations, the USPSTF took into consideration 13 randomized controlled trials in which the mean participant age ranged from 53 to 74 years.6 The new analysis included almost 22,000 participants younger than age 50 and more than 37,000 participants age 70 years and older.6 This gave the USPSTF sufficient data to make a more informed recommendation for the younger age group, including adults ages 40–49 years, and for those over age 70. The evidence showed that aspirin use for the primary prevention of cardiovascular disease decreased myocardial infarction and stroke but not cardiovascular or all-cause mortality.6

The USPSTF also commissioned a microsimulation model to estimate the magnitude of the net benefit of aspirin. This modeling showed that people ages 40–59 years with a 10% or greater 10-year cardiovascular disease risk had a moderate net benefit in quality-adjusted life-years and life-years gained, whereas initiation of aspirin use in people over age 70 was associated with a loss in quality-adjusted life-years and life-years.6 The quality-adjusted life-years gained in people ages 60–69 ranged from slightly negative to slightly positive and depended on the cardiovascular disease risk.6

The USPSTF reviewed 14 randomized controlled trials to assess the harms of low-dose aspirin. Pooled analysis showed that aspirin use was associated with a 58% increase in major gastrointestinal bleeding.6 It also showed an increase in intracranial bleeds in participants taking aspirin, but the treatment was not associated with a statistically significant increase in the risk of fatal hemorrhagic stroke.6 The data did not suggest that the relative risk of bleeding depended on age, but the authors noted that episodes of bleeding do increase with age, particularly in adults age 60 and older.6 This increased bleeding risk is one reason why the ACC/AHA indicates that low-dose aspirin should not be administered on a routine basis for primary prevention of cardiovascular disease in people age 70 and older or any adult at increased bleeding risk.7 The USPSTF agrees that clinicians should consider stopping aspirin use in older adults, particularly around age 75.6

After weighing the benefits and harms of the use of aspirin for the primary prevention of cardiovascular disease, the USPSTF has determined that there is a small net benefit in people ages 40–59 years with a 10% or greater 10-year cardiovascular disease risk, and there is no net benefit in persons age 60 years and older.6

Earn continuing medical education (CME) credits and learn more about the changing guidelines with Pri-Med’s Frankly Speaking Podcast Episode: Aspirin–Not Really for Primary Prevention. Also, know when aspirin might be harmful to older patients in Pri-Med’s Frankly Speaking Podcast Episode: Avoiding Aspirin in the Elderly: More Than Increased Bleeding Risk. Explore these and more cardiovascular CME/CE courses at Pri-Med.com.

 

References

  1. 1. Ittaman SV, VanWormer JJ, Rezkalla SH. The role of aspirin in the prevention of cardiovascular disease. Clin Med Res. 2014;12(3-4):147-54. doi:10.3121/cmr.2013.1197.
  1. 2. Peters AT, Mutharasan RK. Aspirin for prevention of cardiovascular disease. JAMA. 2020;323(7):676. doi:10.1001/jama.2019.18425.

3. Liu EY, Al-Sofiani ME, Yeh H, Echouffo-Tcheugui JB, Joseph JJ, Kalyani RR. Use of preventive aspirin among older US adults with and without diabetes. JAMA Netw Open. 2021;4(6):e2112210. doi:10.1001/jamanetworkopen.2021.12210.

4. O’Brien CW, Juraschek SP, Wee CC. Prevalence of aspirin use for primary prevention of cardiovascular disease in the United States: results from the 2017 National Health Interview Survey. Ann Intern Med. 2019;171(8):596-598. doi:10.7326/M19-0953.

5. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;74(10):e177-e232. doi:10.1016/j.jacc.2019.03.010. Erratum in: J Am Coll Cardiol. 2019;74(10):1429-1430. Erratum in: J Am Coll Cardiol. 2020;75(7):840.

6. United States Preventive Services Task Force. Aspirin use to prevent cardiovascular disease: preventive medication–draft recommendation. Updated October 12, 2021. Accessed February 13, 2022.

7. Orkaby AR, Gaziano JM. Update on aspirin in primary prevention. American College of Cardiology Expert Analysis. Updated November 26, 2019. Accessed February 13, 2022.

8. Gaziano JM, Brotons C, Coppolecchia R, Cricelli C, et al; ARRIVE Executive Committee. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet. 2018;392(10152):1036-1046.

9. ASCEND Study Collaborative Group, Bowman L, Mafham M, Wallendszus K, et al. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med. 2018;379(16):1529-1539.

10. McNeil JJ, Nelson MR, Woods RL, Lockery JE, et al; ASPREE Investigator Group. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly. N Engl J Med. 2018;379(16):1519-1528.

11. American College of Cardiology. ASCVD risk estimator plus. Accessed February 13, 2022.