Here we go again! The Ever-Changing Use of Aspirin for Primary Prevention of Atherosclerotic Cardiovascular Disease

Here we go again! The Ever-Changing Use of Aspirin for Primary Prevention of Atherosclerotic Cardiovascular Disease
Athena Cannon, PharmD, Indian Health Board Medical and Dental Center

Background: The use of low-dose aspirin has found its place in secondary prevention of atherosclerotic cardiovascular disease (ASCVD), however its role in primary prevention of ASCVD is ever-changing and controversial. The mechanism behind aspirin’s potential benefit in the prevention of ASCVD is its irreversible inhibition of cyclooxygenase-1 activity and thromboxane A2 synthesis, which leads to suppression of platelet activation and aggregation. The optimal dosing in support of this mechanism is less than 100mg (81mg in the U.S.). A patient’s 10-year risk of experiencing ASCVD can be calculated using the Pooled Cohort Equations developed by the American College of Cardiology (ACC) /American Heart Association (AHA). While the true benefits of aspirin therapy in primary prevention have been debated, the increased risk of major bleeding with aspirin therapy has been clearly documented. This risk increases in patients who are greater than 70 years old, have a history of gastrointestinal bleeding, chronic kidney disease, coagulopathy, or are on concomitant medications that enhance bleed risk such as non-steroidal anti-inflammatory drugs or anticoagulants.

Recommendations surrounding the use of aspirin in primary prevention have been published by the American College of Chest Physicians in 2012, U.S. Preventive Services Task Force (USPSTF) in 2016, and the ACC/AHA in 2019. With each iteration of guidelines being released, the benefits of aspirin therapy in certain age groups and patient populations have narrowed.

Evidence & Discussion: The 2021 USPSTF Statement on Aspirin Use to Prevent Cardiovascular Disease is the newest recommendation, after the 2019 ACC/AHA Guidelines for Primary Prevention of Cardiovascular Disease. The 2019 ACC/AHA guideline recommends aspirin for primary prevention of ASCVD among adults 40-70 years old who have an ASCVD risk > 10% but are not at increased risk for bleeding. Additionally, aspirin is not recommended on a routine basis for patients > 70 years old or in any patients at increased risk of bleeding.

In a microsimulation model conducted by USPSTF to estimate the magnitude of the net benefit of aspirin for preventing ASCVD, the data suggests that a modest net benefit in quality-adjusted life and life-years gained is seen in patients 40-59 years old with a > 10% 10-year ASCVD risk. The benefits of initiating aspirin use are greater for individuals at higher risk for future ASCVD which was identified to be those with > 15% or > 20% 10-year ASCVD risk. Conversely, a range of slightly positive and slightly negative impacts on the quality-adjusted life-years gained was seen in patients 60-69 years old, and an overall loss of both quality-adjusted life-years and life-years was seen in patients 70-79 years old.

The 2021 USPSTF Statement concluded that the decision to initiate aspirin in patients 40-59 years old for primary prevention should be an individual decision based on clinician and patient discussion of risks and benefits. Furthermore, they recommend that aspirin should not be initiated in patients > 60 years old and consideration for stopping treatment should occur around 75 years old.

Clinical Impact: Healthcare providers should recognize the ever-changing guidance surrounding aspirin use for primary prevention and consider patient specific characteristics (age, risk of ASCVD, and risk of bleed) when deciding to initiate therapy. The release of the 2021 USPSTF recommendations may decrease the initiation of aspirin in patients greater than 60 years old and lead to the discontinuation of aspirin at 75 years old or sooner depending on when risk of aspirin therapy outweighs potential benefits.


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