This article is first seen at Medscape.
Citation: Daily Aspirin Challenged in Primary Stroke Prevention: ASPREE – Medscape – Jul 28, 2023
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A sizable randomized trial tracking seniors over around 5 years has revealed that taking low-dose aspirin daily for primary prevention did not lead to a reduction in the risk of initial strokes. However, participants who consumed 100 mg/d of aspirin witnessed a notable 38% increase in the risk of intracranial (IC) bleeding. Rates of both ischemic and hemorrhagic strokes remained consistent between the aspirin group and the control group.
The excess instances of IC bleeding included hemorrhagic strokes, as well as dural and subdural bleeds reminiscent of traumatic head injuries, potentially from falls. These findings were based on a secondary analysis of the ASPREE trial. Importantly, these results were consistent across age, gender, and cardiovascular risk factors.
This study has cast a shadow on aspirin’s reputation as a safeguard against cardiovascular events for individuals with no history of stroke or clinical heart disease. This study suggests that the potential benefits of aspirin in primary prevention are counterbalanced by an elevated risk of major bleeding.
The main clinical outcomes of the ASPREE trial, published in multiple papers in 2018, indicated that low-dose aspirin for primary prevention failed to extend survival free from physical or mental disability over a 5-year period. The study also highlighted significant associations between daily aspirin use and the risk of major bleeding, particularly upper gastrointestinal bleeding, along with increased overall mortality.
Conducted in Australia and the United States, the ASPREE trial enrolled 19,114 participants from the community aged 70 years or older, or at least 65 for those in the US identifying as Black or Hispanic.
The secondary analysis of ASPREE reported that aspirin recipients experienced 20 fewer ischemic strokes but faced an additional 29 IC bleeding events. Although absolute numbers of hemorrhagic and non-hemorrhagic events were small, senior author John J. McNeil from Monash University in Melbourne, Australia, pointed out that numerically, the bleeding events outweighed any potential prevention of ischemic events.
The ASPREE trial, along with other studies that have cast doubt on aspirin’s efficacy in primary prevention, raises questions about the rationale behind long-term prescriptions, considering the multitude of short-term risks that need to be addressed. This perspective supports the recommendation of last year’s US Preventive Services Task Force against routine prescription of low-dose aspirin for primary prevention, particularly in adults aged 60 and older.
Among the noteworthy aspects of the analysis, McNeil highlighted the segregation of stroke and nonstroke IC bleeding events based on anatomical locations.
Intracranial bleeds overall, as well as subdural, extradural, and subarachnoid bleeds likely due to trauma, were more prevalent in the aspirin group. However, these differences did not reach statistical significance due to their low incidence rates.
McNeil underscored the study’s significance in exposing an unnoticed risk of aspirin, encompassing IC bleeding, particularly in older individuals more prone to bleeding and head trauma.
While there were no substantial differences in overall strokes or separate ischemic and hemorrhagic strokes, hazard ratios for IC bleeding risk, which included hemorrhagic stroke, were significantly elevated in the aspirin group.
Additionally, hazard ratios for nonstroke IC bleeding exhibited an upward trend:
- All stroke: 0.97 (95% confidence interval [CI], 0.79 – 1.18; P = .04)
- Ischemic stroke: 0.89 (95% CI, 0.71 – 1.11; P = .28)
- Hemorrhagic stroke: 1.33 (95% CI, 0.87 – 2.04; P = .19)
- All IC bleeding: 1.38 (95% CI, 1.03 – 1.84; P = .03)
- Nonstroke IC bleeding: 1.45 (95% CI, 0.98 – 2.16; P = .07)
Berger, NYU Langone Hospitals and director of the Center for the Prevention of Cardiovascular Disease at NYU Grossman School of Medicine, New York City, emphasized the need for precision-based medicine to determine aspirin candidates. He questioned why platelet activity measurement, similar to the measurement of blood pressure and lipids, is not implemented for aspirin’s guidance.
Berger envisages a future where platelet activity or genetics could determine aspirin’s benefits. He suggested that rather than conducting another broad-based aspirin trial for primary prevention, the focus should shift towards understanding the drug’s mechanism of action and selecting appropriate populations.
Link to the full Article (Medscape):
Link to the full PDF Article: Effect of Aspirin on All-Cause Mortality in the Healthy Elderly
https://www.nejm.org/doi/pdf/10.1056/NEJMoa1803955?articleTools=true
