according to results from a large randomized trial.
The findings, published in JAMA Network Open, bolster recommendations published in 2022 by the U.S. Preventive Services Task Force against daily aspirin for primary prevention of stroke in older adults and add to a mounting consensus that it should be avoided in the healthy elderly, for whom bleeding risks outweigh potential benefits.
Stroke was a preplanned secondary outcome of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which randomized 19,114 community-living people in Australia and the United States (56% women, 91% White) to 100 mg. daily aspirin or placebo. Participants were aged 70 and older, with the exception of U.S. Black and Hispanic individuals, who could be as young as 65. Participants did not have disability or known cardiovascular disease at baseline, and blood pressure was adequately controlled.
ASPEE findings
In 2018 the ASPREE authors, led by John McNeil, PhD, of Monash University, Melbourne, published their findings that aspirin did not reduce mortality or cardiovascular events (including stroke) in the same large cohort.
The new analysis, led by Geoffrey Cloud, MB, BS, of Monash University, focuses on stroke and intracranial bleeding outcomes. At 5 years’ follow up, the ASPREE investigators saw no significant reduction in ischemic stroke incidence associated with aspirin (hazard ratio, 0.89; 95% confidence interval, 0.71-1.11), while incidence of all types of intracranial bleeding, including hemorrhagic stroke, was significantly increased (HR, 1.38; 95% CI, 1.03-1.84).
Altogether 108 of participants taking aspirin (1.1%) experienced some form of intracranial bleeding (subdural, extradural, and/or subarachnoid), compared with 79 (0.8%) in the placebo group. Aspirin-treated patients also saw more hemorrhagic stroke (0.5% vs. 0.4%). As the ASPREE investigators had reported in an earlier paper, upper gastrointestinal bleeding occurred in significantly more aspirin-treated patients than those on placebo (HR, 1.87; 95% CI, 1.32-2.66).
“These outcomes may alter the balance of risks and benefits of an antiplatelet drug, especially if given to individuals at low risk in a primary prevention setting. This concern is relevant given the high stroke risk in older individuals, worldwide increases in populations of older individuals, and the importance of evaluating preventive strategies in this age group,” the investigators wrote.
The investigators cited the study’s large size as a strength while noting among its weaknesses that fewer stroke and bleeding events occurred during follow-up than expected, and that not all ischemic stroke events among older participants were thoroughly investigated.
Patients need to know their risk
In an interview, Shlee Song, MD, director of the stroke center at Cedars-Sinai, Los Angeles, said that the new ASPREE findings underscore the importance of careful communication with patients and their families, who may be confused about which risk group they belong to and either cease taking aspirin when it is in fact indicated, or take it when it could harm them.
“We need to be clear for our patients whether these results are relevant to them or not,” Dr. Song said. “People with a history of ischemic stroke need to know aspirin therapy is helpful in reducing risk of another stroke.”
Some patients may come to believe that because their stroke occurred a long time ago, they are in a lower-risk group. “But people need to understand that with a history of a heart attack or stroke, you’re always a separate group,” Dr. Song said. “Our job is also surveillance screening – have you had a fall this past year? Have you had a change in bowel movements? The bleeding events seen in ASPREE include bleeding in the head and bleeding in the gut.”
A key issue to stress with patients, Dr. Song said, is blood pressure management. “Patients might take aspirin because a family member had a stroke, without controlling blood pressure first. That could be the perfect storm for a head bleed: uncontrolled hypertension and an antiplatelet agent.”
The ASPREE study was funded by the National Institutes of Health in the United States and Monash University and the Victorian Cancer Agency in Australia. Three coauthors reported receiving funding or fees from drug manufacturers. Dr. Song disclosed no financial conflicts related to her comments.