Analytic plan
REGRESSION, EVENT, SECONDARY
Descriptive statistics of the sample were computed overall and by frailty status.The FI was first validated by assessing the association between FI level and risk of mortality over follow‐up using Cox regression (Searle et al., For the primary outcome of incident frailty, we excluded those who were frail at study baseline and conducted an interval‐censored survival analysis for incident frailty using FI >0.2 as the cut point for frailty. Cumulative incidence curves for drug group versus placebo were run using logistic regression, adjusting for time point, drug group, a variable indicating qualifying MI event, and a variable indicating randomization status. These curves were repeated stratified by on‐treatment reduction of CRP and IL‐6 by more than the median at 3 months after study drug initiation, as this has previously been shown to identify greater benefit for cardiovascular endpoints in the trial (Ridker et al., For the secondary outcome of functional impairment, change in self‐reported mobility, self‐care, and usual activity was plotted over time and then stratified by frailty status as baseline frailty has been shown to be an effect modifier of function (Butt, Dewan, Merkely, et al., For the analysis of the main trial outcome stratified by frailty, we reran the primary intention to treat time to event analysis, using pairwise comparisons of individual dose groups with the placebo group, as well as any drug versus placebo and stratified the results by frailty level (nonfrail, prefrail, and frail).All models were run in SAS 9.4.