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The role of Lipoprotein(a) and oxidized phospholipids in modifying the effects of aspirin on major cardiovascular events and bleeding in the ASPirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial: Statistical analysis plan.

Wolfe, R.; Bhatia, H.; Lacaze, P.; Orchard, S. G.; Owen, A.; Polekhina, G.; Yu, C.; Woods, R. L. L.; Tonkin, A.; Tsimikas, S.

2026-05-20 cardiovascular medicine
10.64898/2026.05.17.26353443 medRxiv
Show abstract

Lipoprotein(a) (Lp(a)) is associated with atherothrombosis through several mechanisms, including putative antifibrinolytic properties. In the ASPREE randomized trial of daily low-dose aspirin for primary prevention in older adults, 72% of trial participants in Australia provided baseline blood samples from which Lp(a) and related oxidized phospholipids and plasminogen have been measured in a specialized laboratory at University of California San Diego. Recent findings from our group suggest that aspirin may benefit older individuals with genotypes associated with elevated lipoprotein(a). We present an analysis plan to address key hypotheses relating to whether the effects of aspirin on cardiovascular disease might vary based on a person's measured levels of lipoprotein(a), oxidized phospholipid levels present on protein carriers apoB-100 (OxPL-apoB), Lp(a) (OxPL-apo(a)) and plasminogen (OxPL-PLG), and plasminogen. The analysis plan also articulates safety analyses involving major hemorrhage.

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