Aspirin’s potential contribution to the primary prevention of lipoprotein(a)-mediated atherothrombotic events was unknown. In the context of primary prevention, researchers, for a study, examined the potential advantages of low-dose aspirin for those with increased plasma lipoprotein(a)-associated genotypes.

The study examined 12,815 genotyped participants in the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial of 100 mg/d aspirin who were ≥70 years, of European ancestry, and had no prior cardiovascular disease events. Using rs3798220-C carrier status and quintiles of lipoprotein(a) genomic risk score (LPA-GRS), they determined lipoprotein(a)-associated genotypes. In Cox proportional hazards models for incidence of major adverse cardiovascular events (MACE) & clinically severe bleeding, they looked for interactions between genotypes & aspirin allocation. They separately looked at connections in the trial’s aspirin and placebo arms.

A correlation between the genotype rs3798220-C and aspirin allocation was found (P=0.049) throughout a follow-up period of a median of 4.7 years (IQR: 3.6–5.7 years) and 435 MACE. However, the aspirin group (HR: 0.54; 95% CI: 0.17-1.70) did not show an association between rs3798220-C carrier status and higher MACE risk (HR: 1.90; 95% CI: 1.11-3.24). High LPA-GRS (vs. low LPA-GRS) was linked to a higher risk of MACE in the placebo group (HR: 1.70; 95% CI: 1.14–2.55), whereas the risk was reduced in the aspirin group (HR: 1.41; 95% CI: 0.90–2.23). However, the interaction was not statistically significant. Aspirin increased clinically significant bleeding and decreased MACE by 1.7 occurrences per 1,000 person-years in each group. Aspirin decreased MACE by 11.4 and 3.3 occurrences per 1,000 person-years, respectively, in the rs3798220-C and high LPA-GRS subgroups, without noticeably raising the bleeding risk.

Older people with increased lipoprotein(a) genotypes may benefit from aspirin for primary prevention.

Reference: jacc.org/doi/10.1016/j.jacc.2022.07.027

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