In older adults with high polygenic risk, daily aspirin reduced ischemic stroke by 51% (HR 0.49; 95% CI 0.28-0.85) without significantly increasing major bleeding.
RCT (n=12,031)
placebo-controlled
randomized
Does aspirin 100 mg daily reduce ischemic stroke in older adults (>70 years) without prior cardiovascular disease stratified by polygenic risk?
High polygenic risk scores can identify a subgroup of older adults who derive a net benefit from daily low-dose aspirin for the primary prevention of ischemic stroke without excess bleeding.
Effect estimate: HR 0.49 (95% CI 0.28-0.85)
BACKGROUND: Low-dose aspirin is no longer recommended for routine primary prevention in older adults due to bleeding risks outweighing vascular benefits. We hypothesized that an integrative polygenic score (iPGS) could identify a subgroup of older individuals who derive net benefit from aspirin for the primary prevention of ischemic stroke. METHODS: We performed post hoc analysis of the ASPREE randomized, placebo-controlled trial (Aspirin in Reducing Events in the Elderly) of daily 100-mg aspirin, in 12 031 genotyped participants of European ancestry aged >70 years without prior cardiovascular disease. The iPGS was derived from >1.2 million variants and evaluated both continuously and by quintiles. Cox models assessed associations between polygenic risk, ischemic stroke, and major bleeding events, and tested the interaction between the iPGS and treatment allocation, with adjustment for baseline lifestyle and clinical covariates. RESULTS: =0.04) but not major bleeding. In the highest iPGS quintile, aspirin reduced ischemic stroke by 51% (hazard ratio, 0.49 95% CI, 0.28-0.85) without significantly increasing major bleeding (hazard ratio, 1.15 95% CI, 0.71-1.88). No benefit was observed in the overall cohort or in lower-risk quintiles. CONCLUSIONS: Among older adults, high polygenic risk identifies individuals who may experience substantial stroke reduction with aspirin, with no excess bleeding. These findings raise the possibility that genomic risk stratification may enable targeted aspirin use for the primary prevention of ischemic stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.
Yu et al. (Fri,) conducted a rct in Primary prevention of ischemic stroke (n=12,031). Aspirin vs. Placebo was evaluated on Ischemic stroke in the highest iPGS quintile (HR 0.49, 95% CI 0.28-0.85). In older adults with high polygenic risk, daily aspirin reduced ischemic stroke by 51% (HR 0.49; 95% CI 0.28-0.85) without significantly increasing major bleeding.