Timing of oral beta-blocker initiation and 90-day mortality in critically ill patients with acute myocardial infarction: a target trial emulation

Abstract Oral beta-blockers are used after acute myocardial infarction (AMI), but the optimal timing of initiation in critically ill patients is uncertain, and observational early-versus-late comparisons are prone to immortal-time bias. We emulated a target trial of early (≤ 24 h) versus delayed (> 24–72 h) oral beta-blocker initiation in beta-blocker–naïve ICU patients with AMI in MIMIC-IV ( n  = 5,899), using a clone–censor–weight design with stabilized inverse-probability-of-censoring weights and a subject-level cluster bootstrap; the primary outcome was 90-day all-cause mortality as an IPCW-weighted cumulative risk. We found no robust evidence of a difference in 90-day mortality between the strategies (25.7% vs. 25.2%; risk difference [RD] 0.53% points, 95% CI − 2.13 to 3.43); this interval is compatible with differences in either direction and does not establish equivalence. In an exploratory 7-day analysis the RD was negative under the early strategy (− 2.13% points; unadjusted 95% CI − 3.64 to − 0.21), but this window was one of several, was not robust to multiplicity adjustment, and cannot be interpreted causally. Effect modification by baseline vasoactive support could not be estimated reliably. In critically ill AMI, the timing of oral beta-blocker initiation was not robustly associated with 90-day mortality.