New Analysis: Daily Low-Dose Aspirin Not Beneficial for Preventing a First Stroke in Healthy Older Adults

Often caused by blood clots, heart diseases (including heart attack) and stroke are the first and fifth leading causes of death in the United States, respectively.[1] Low-dose aspirin, ranging from 75 to 100 milligrams (mg), also called baby aspirin (such as BAYER ASPIRIN, ECOTRIN and generics), can lower the risk of heart attack and stroke. This is because aspirin inhibits the aggregation of platelets (blood cells that clump together to form blood clots that can block blood vessels). However, due to its tendency to cause internal bleeding, especially when used on a regular basis, aspirin’s potential benefits should be weighed against its bleeding-related harms.[2]

For most people who already have had a heart attack or stroke, the Food and Drug Administration (FDA) recommends the routine use of low-dose aspirin because strong evidence shows that the benefits for preventing a second heart attack or stroke (which is called secondary prevention) exceed the potential harms.

In contrast, the FDA does not recommend regular use of low-dose aspirin for preventing a first heart attack or stroke in individuals with no history of heart attack or stroke (which is called primary prevention) because there is no strong evidence supporting the net benefits of such use.

A recent analysis of data from the large-scale, federally funded ASPREE trial showed that the use of low-dose aspirin by healthy older adults does not provide significant protection against the occurrence of a first stroke resulting from blood clots, but increases the risk of bleeding in the brain. The analysis was published in JAMA Network Open in July 2023.

The new analysis[3]

ASPREE was a randomized clinical trial that enrolled 19,114 subjects living in either Australia or the United States, whose age was 70 or older (65 or older in case of U.S. subjects who self-reported their ethnicity or race as Hispanic or African American). Fifty-six percent of these subjects were female. Before the trial began, all subjects did not have a history of heart disease, stroke, dementia or physical disability.

In the trial, 9,525 subjects were randomly assigned to receive a daily dose of 100 mg of enteric-coated aspirin — a type of aspirin that mostly dissolves in the intestines (instead of the stomach) to decrease the risk of gastrointestinal ulcers and bleeding — and the remaining 9,589 subjects received a matching placebo.

After a median of five years of follow-up, the new analysis found that 195 (4.6%) of the subjects treated with aspirin developed a first stroke compared with 203 (4.7%) of those in the placebo group, a small difference that was not statistically significant.

In contrast, 108 (2.5%) of the subjects in the aspirin group experienced a first episode of bleeding in the brain, compared with 79 (1.8%) of those in the placebo group, a difference that was statistically significant. These episodes of brain bleeding led to hospitalization, prolonged hospitalization, surgery or death.

Further analyses showed that among every 1,000 subjects taking low-dose aspirin over five years, there were 2.5 fewer strokes at the expense of 3.5 cases of bleeding in the brain, a difference that was not statistically significant. Given these results, the investigators concluded that aspirin should not be used to prevent a first stroke among healthy older adults. Notably, the increased risk of brain bleeding is particularly concerning because older adults are at increased risk of head trauma, usually caused by falls.

The new analysis supports a 2018 analysis of data from the ASPREE trial, which showed that subjects treated with aspirin did not have a lower rate of cardiovascular disease (defined as fatal coronary heart disease, nonfatal heart attack, fatal or nonfatal stroke, or hospitalization for heart failure).[4] In contrast, that analysis found a significantly higher risk for major bleeding, especially in the upper gastrointestinal tract, among subjects treated with aspirin. These findings provide additional evidence that low-dose aspirin should not be used for the primary prevention of stroke or cardiovascular disease in healthy older adults.

What You Can Do

To help reduce your risk of cardiovascular disease, eat a balanced, mostly plant-based or Mediterranean diet, exercise regularly and do not smoke.[5] If you have diabetes, high blood pressure or high cholesterol, make sure that these conditions are being appropriately controlled.

If you have had a heart attack, stroke or other cardiovascular event or have a history of coronary artery surgery or stent (insertion of a metal mesh coil) procedure, you should be taking low-dose aspirin daily to prevent another heart attack or stroke. The exception to using aspirin in these cases is if you are allergic to aspirin, at high risk of bleeding, drink alcohol regularly or are undergoing a dental or medical procedure.

However, if you are a healthy older adult without a history of heart attack or stroke, it is best not to start using low-dose aspirin to prevent a first heart disease or stroke. If you are already taking daily low-dose aspirin, consult your clinician because stopping this drug suddenly can trigger a heart attack or stroke due to a blood clot.[6]
 

References

[1] Centers for Disease Control and Prevention. Heart disease and stroke. September 8, 2022. https://www.cdc.gov/chronicdisease/resources/publications/factsheets/heart-disease-stroke.htm. Accessed November 22, 2023.

[2] Food and Drug Administration. Use of aspirin for primary prevention of heart attack and stroke. December 30, 2016. https://www.fda.gov/drugs/information-consumers-and-patients-drugs/use-aspirin-primary-prevention-heart-attack-and-stroke. Accessed November 22, 2023.

[3] Cloud GC, Williamson JD, Thao LTP, et al. Low-dose aspirin and the risk of stroke and intracerebral bleeding in healthy older people: Secondary analysis of a randomized clinical trial. JAMA Netw Open. 2023;6(7):E2325803.

[4] McNeil JJ, Wolfe R, Woods RL, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med. 2018;379(16):1509-1518.

[5] Arnett DK, Blumenthal RS, Albert MA, 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. Circulation. 2019;140(11):e596-e646.

[6] Sundström J, Hedberg J, Thuresson M, et al. Low-dose aspirin discontinuation and risk of cardiovascular events: A Swedish nationwide, population-based cohort study. Circulation. 2017;136(13):1183-1192.