Low-dose aspirin is no longer routinely recommended for primary prevention in older adults because bleeding risks often outweigh benefits. But new data suggest that polygenic risk scores might 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, researchers 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.
The integrative polygenic score was derived from more than 1.2 million variants. During follow-up, 187 ischemic strokes and 373 major bleeding events occurred. 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.
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. This benefit was not accompanied by a statistically significant increase in major bleeding.
No aspirin benefit was observed in the overall cohort or in lower polygenic risk quintiles. The findings suggest 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.