Abstract
BACKGROUND: Chronic low-grade inflammation is hypothesised as a central driver of frailty. This study aims to evaluate whether low-dose aspirin can reverse frailty status among initially prefrail/frail older adults. METHODS: This was a post hoc subgroup analysis of the Aspirin in Reducing Events in the Elderly (ASPREE), a randomised, placebo-controlled trial, involving community-dwelling adults aged ≥65 years. The median (Interquartile range) follow-up was 4.7 (3.6-5.7) years. We included participants who were prefrail or frail at baseline, with frailty assessed using two validated measures: the Fried Frailty Phenotype (FFP) and the Deficit-Accumulation Frailty Index (FI). Frailty reversal was defined as a transition to a less severe state (from frail to prefrail/nonfrail, prefrail to nonfrail). The discrete-time survival model was used for outcome analysis; linear mixed-effects models compared longitudinal frailty trajectories between the treatment arms. RESULTS: Among 6595 and 8766 participants included in the FFP and FI analyses, respectively, there was no significant difference in frailty status reversal between aspirin and placebo groups (FFP-HR: 1.00, 95% CI: 0.92-1.07; FI-HR: 1.00, 95% CI: 0.94-1.07). No significant difference was found in the change of FFP counts (β = 0.014, SE = 0.007, P = .06) and FI score (β = 0.0004, SE = 0.004, P = .37) between the aspirin and placebo groups over time, suggesting that aspirin neither reversed nor worsened frailty severity. Subgroup analyses revealed no effect modification by frailty risk factors such as age, sex, race and medical history. CONCLUSION: Low-dose aspirin has no effect in reversing frailty among prefrail and frail individuals. The findings highlight the need to explore alternative anti-inflammatory medications for frailty management.