POLYGENIC risk may identify older adults most likely to benefit from aspirin for ischemic stroke prevention.
Polygenic Risk Identifies Aspirin Benefit
Low dose aspirin is no longer recommended for routine primary prevention in older adults because bleeding risks often outweigh vascular benefits. New data suggest that polygenic risk may help identify a subgroup of older individuals who could still derive meaningful protection against ischemic stroke.
In a post hoc analysis of the randomized, placebo controlled ASPREE trial, investigators evaluated whether an integrative polygenic score could stratify aspirin benefit for primary prevention of ischemic stroke. The analysis included 12,031 genotyped participants of European ancestry aged over 70 years, all without prior cardiovascular disease. Participants were assigned to daily 100 mg aspirin or placebo and followed for a median of 4.6 years.
Ischemic Stroke Risk Rose with Genetic Burden
The integrative polygenic score was derived from more than 1.2 million variants and assessed continuously and by quintiles. During follow up, 187 ischemic strokes and 373 major bleeding events occurred, including 101 intracranial bleeds and 46 hemorrhagic strokes.
Each 1 SD increase in the polygenic risk score was associated with a higher risk of incident ischemic stroke, with a hazard ratio of 1.39. This suggests that genomic risk stratification may capture clinically relevant ischemic stroke susceptibility in older adults who otherwise would not be selected for aspirin on the basis of conventional primary prevention criteria alone.
Targeted Aspirin Use Shows Promise
A treatment interaction was observed between continuous polygenic risk and aspirin allocation for ischemic stroke, but not for major bleeding. In the highest polygenic risk quintile, aspirin reduced ischemic stroke by 51%, with a hazard ratio of 0.49. Importantly, this benefit was not accompanied by a statistically significant increase in major bleeding, with a hazard ratio of 1.15.
No aspirin benefit was observed in the overall cohort or in lower polygenic risk quintiles. The findings raise the possibility that aspirin use in older adults may need to shift from broad avoidance toward more selective, genomically informed prescribing. However, the analysis was post hoc and restricted to participants of European ancestry, meaning clinical implementation would require further validation in broader populations.
Reference
Yu C et al. Polygenic Risk Identifies Older Adults Who May Benefit from Aspirin for the Primary Prevention of Ischemic Stroke. Stroke. 2026; DOI: 10.1161/STROKEAHA.125.054979.
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