Expanded statistical analysis plan for legacy and long-term effects of aspirin in the ASPREE-XT observational follow-up study of participants in the ASPREE randomized trial

The ASPREE randomized controlled trial (2010–2017) of 19,114 community-dwelling older adults without cardiovascular disease and significant disability compared daily 100mg aspirin to placebo. A total of 16,317 (93%) of 17,546 surviving and non-withdrawn participants agreed to continue regular study follow-up visits in the post-trial phase, named ASPREE-XT (2017–2024). We present a statistical analysis plan to underpin three main papers to report aspirin effects through to the fourth post-trial ASPREE-XT study visit with focus areas of: (1) death, dementia, and disability, (2) CVD events and bleeding, and (3) cancer. The focus of the plan is to estimate long-term (entire timespan of RCT plus post-trial) and legacy (post-trial period only) effects of aspirin in the setting of primary prevention for older individuals. Preliminary insights to these effects are presented that are based on data that has been reported to the study’s observational study monitoring board however formal data lock is not expected until October 2023.