Almost 30 million Americans take aspirin for primary or secondary prevention of cardiovascular disease (CVD) or colorectal cancer (CRC).1 For decades, aspirin has been recommended as primary prevention for patients at risk for CVD, despite the attendant increased risk of major bleeding.2 However, the results of recent clinical trials have challenged the clinical risk-to-benefit trade-off of daily aspirin use.
The most recent recommendations from the US Preventive Services Task Force (USPSTF) have abandoned the routine recommendation for daily aspirin use for primary prevention of CVD.3 Continue reading to learn more about the potential benefits and harms of daily aspirin use.
What Are the Potential Benefits of Daily Aspirin?
Aspirin has been used for its antipyretic and analgesic properties long before it came into use to prevent or treat CVD. After the discovery of aspirin’s antiplatelet and antithrombotic effects, researchers began to explore the possibility of using it to prevent and treat acute coronary syndrome and stroke.2
At low doses, aspirin is an irreversible inhibitor of cyclo-oxygenase-1 (COX-1), which inhibits platelet function.3 In patients with pre-existing CVD, aspirin can reduce the risk of experiencing a CVD event by 21% and all-cause mortality by 13%. However, the benefit of daily low-dose aspirin use in patients without pre-existing CVD (primary prevention) is less clear.1,3
Although the systematic review commissioned by the USPSTF found that daily low-dose aspirin is associated with a clinically significant reduction in absolute risk of CVD events, it is a modest reduction, with an odds ratio (OR) of 0.9.4
Daily Aspirin Use: Current USPSTF Recommendations to Prevent Cardiovascular Disease
New studies have highlighted the potential for daily aspirin to cause harm. In 2022, the USPSTF released new recommendations on the use of aspirin for the primary prevention of CVD.3 The new recommendations are as follows5:
- For adults between 40 and 59 years of age with a 10% or greater 10-year CVD risk, the Task Force recommends that the decision to start aspirin therapy be an individual one. This recommendation is offered as a grade C recommendation, with moderate certainty of a small benefit.5
- For adults older than 60 years, the Task Force recommends against starting low-dose aspirin therapy. This recommendation is offered as a grade D recommendation, which recommends against using aspirin for this population.5
These recommendations apply to adults older than 40 years of age without signs or symptoms of CVD and not at increased risk for bleeding.
What Changed From the Previous USPSTF Recommendations?
The 2016 USPSTF recommendations had stronger recommendations for the use of aspirin to prevent CVD and CRC. The new recommendations concluded that there was insufficient evidence that low-dose daily aspirin reduces the incidence of or mortality from CRC.3 Therefore, the new recommendations only address daily aspirin use for the primary prevention of CVD.
The previous recommendations advised initiating daily aspirin use for adults aged 50 to 59 years with a 10% or greater 10-year CVD risk without increased risk for bleeding, who have a life expectancy of 10 years or greater, and who are willing to take daily low-dose aspirin for at least 10 years. This recommendation was also a higher grade (Grade B — high certainty of a moderate benefit) compared with the updated recommendations.6
In the 2016 USPSTF recommendations, the Task Force recommended an individual decision for initiating aspirin use for adults aged 60 to 69 years with a 10% or greater 10-year CVD risk. This recommendation was offered as a grade C recommendation.6
The previous recommendations cited insufficient evidence for daily aspirin use in adults younger than 50 years and older than 70 years.6 The updated recommendations have addressed patients as young as 40 years.3
Why Did the USPSTF Recommendations Change?
New data on the potential risk of aspirin have prompted the change in the USPSTF recommendations on daily aspirin use for primary prevention of CVD. The primary risk of daily aspirin use is an increased risk of major bleeding such as gastrointestinal bleeding, intracranial bleeding, and hemorrhagic stroke.4
The factor contributing to the increased risk of bleeding is aspirin’s inhibition of platelet activity. Additionally, by inhibiting COX-1, aspirin may promote gastrointestinal bleeding by inhibiting the production of several prostaglandins that protect the gastrointestinal mucosa.3
Since the 2016 USPSTF recommendations, 3 trials have been published with a focus on special populations of patients, including those with older age, diabetes, and additional CVD risk factors.7-9
Aspirin Use in Older Adults
A randomized, placebo-controlled clinical trial (ASPREE; ClinicalTrials.gov Identifier: 01038583) of more than 19,000 adults older than 70 years in Australia and the United States found that, compared with placebo, enteric-coated aspirin 100 mg resulted in a significantly higher risk of major bleeding. Additionally, aspirin 100 mg/d was not associated with a significantly lower risk of CVD compared with placebo.7
Aspirin Use in Adults With Diabetes
A randomized, placebo-controlled trial (ASCEND; ClinicalTrials.gov Identifier: NCT00135226) of more than 15,000 adults with diabetes but without CVD found that, compared with placebo, aspirin 100 mg/d significantly reduced the risk of CV events (8.5% in the aspirin group vs 9.6% in the placebo group; P=.01). However, the authors concluded that these benefits were counterbalanced by the increased risk of bleeding (4.1% in the aspirin group vs 3.2% in the placebo group; P=.003).8
Aspirin Use in Adults at Moderate Risk for CVD
The Aspirin to Reduce Risk of Initial Vascular Events (ARRIVE; ClinicalTrials.gov Identifier: NCT00501059) study was a randomized, placebo-controlled trial of more than 12,000 adults at moderate risk for CVD (defined as a 10% to 20% 10-year risk). Due to a lower-than-expected event rate, the authors were unable to address the role of aspirin in the primary prevention of CVD in a moderate-risk population. However, the results were consistent with the results from other trials with a low-risk population.9
Updated Evidence Report and Systematic Review for the USPSTF
The systematic review commissioned by the USPSTF included 11 randomized controlled trials (including the studies discussed above) and 1 pilot trial with more than 134,000 patients. The authors of this systematic review found that although low-dose aspirin was associated with a small reduction in CV events, it was also associated with small increases in major bleeding events.4
The results for aspirin use for the prevention of CRC were not as robust as those for primary CVD prevention and were highly variable.4
Authors of another systematic review and meta-analysis from 2019 on the association of aspirin use with CV events and bleeding events found that the absolute risk reduction of CV events (0.41%) did not outweigh the increased risk of major bleeding (0.47%).10
Implementing USPSTF Daily Aspirin Recommendations Into Practice
The 2022 USPSTF recommendations align with the position of other professional organizations and guidelines, including11-13:
- 2019 American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease — available here11; and
- 2021 European Society of Cardiology (ESC) Guidelines on Cardiovascular Disease Prevention in Clinical Practice — available here.12
The American Academy of Family Physicians (AAFP) has also released a statement supporting the USPSTF recommendations on aspirin use for the primary prevention of CVD.13
Shared Decision-Making
Aspirin use is no longer routinely recommended for any patient. Initiating daily aspirin use should be based on shared decision-making between patients and their health care providers. It is important to determine what factors are most important for patients when making this treatment decision.3
Patients who choose to initiate aspirin may place a higher value on aspirin’s benefit of decreasing the risk of CV events and stroke than the increased risk of bleeding. For these patients, clinicians can recommend low-dose aspirin (< 100 mg/d). The most common aspirin dosage for this purpose is 81 mg/d.3
Patients who choose not to initiate aspirin may place a higher value on the increased risk of bleeding and the increased pill burden of daily aspirin.3
Clinicians should educate patients about the increased risk of bleeding, including signs and symptoms to watch for, such as3,14,15:
- Severe headache;
- Dizziness;
- Nausea and vomiting;
- Seizures;
- Weakness on 1 or both sides;
- Fatigue;
- Aphasia;
- Black, tarry stool;
- Coffee ground vomit;
- Abdominal cramping; and
- Pallor.
Re-evaluating Patients Taking Daily Aspirin
Patients currently taking aspirin daily should be regularly evaluated to ensure the benefit of treatment still outweighs the risk. The risk of serious bleeding increases with age. Modeling data from the USPSTF shows that it may be reasonable to stop daily aspirin use at the age of 75 years.3
Alternative Approaches to Primary CVD Prevention
Other approaches to the primary prevention of CVD should also be considered. Other therapies with a more favorable safety profile than aspirin include antihypertensive agents and statin therapy.1
In the future, it may be possible to identify distinct populations of patients that may benefit from aspirin therapy, such as those with hyperactive platelets. However, more research is needed to determine the potential benefit to these patients.1
This article originally appeared on The Cardiology Advisor.
