Early Dexmedetomidine in Ventilated Acute Myocardial Infarction: A Target Trial Emulation Using MIMIC-IV

Background : Sedation choice may influence outcomes in acute myocardial infarction (AMI) patients requiring invasive mechanical ventilation (IMV). Dexmedetomidine (DEX) provides arousable sedation with sympatholytic effects and is guideline‑endorsed, but data in ventilated AMI patients—particularly for intermediate‑term mortality—are limited. Objective : To evaluate the association between early DEX initiation and 90‑day all‑cause mortality among AMI patients starting IMV. Design, setting, and participants : Retrospective cohort and target trial emulation using the MIMIC‑IV database (2008–2022). Adults with AMI admitted to the ICU who initiated their first IMV episode within 7 days were included. Time zero (t0) was the start of IMV. Admissions involving cardiac surgery or LVAD procedures were excluded. The final analytic cohort comprised 2,056 patients (270 received early DEX). Exposure : Early DEX, defined as initiation within 24 hours after t0, versus no early DEX. Main outcomes and measures: The primary outcome was 90‑day all‑cause mortality from t0. The secondary outcome was ventilator‑free days to day 28 (VFD‑28). The primary analysis used a covariate‑balancing propensity score (CBPS) with stabilized inverse probability weights and a weighted Cox model with robust, patient‑clustered standard errors. Prespecified sensitivity analyses included IPTW‑Cox with weight truncation, targeted maximum likelihood estimation (TMLE), 30‑day mortality, exclusion of out‑of‑hospital cardiac arrest (OHCA). Results : Among 2,056 eligible patients, early DEX use was associated with a lower hazard of 90‑day mortality (HR 0.562; 95% CI 0.433–0.730; p<0.001) and more ventilator‑free days (mean difference 4.98 days; 95% CI 4.01–5.95; p<0.001). Sensitivity analyses were directionally consistent: IPTW‑Cox HR 0.603 (95% CI 0.468–0.777; p=0.0001); TMLE risk ratio 0.864 (95% CI 0.805–0.927; p<0.001); 30‑day mortality HR 0.453 (95% CI 0.332–0.619; p<0.001); OHCA‑excluded HR 0.598 (95% CI 0.452–0.792; p=0.0003). Post‑weighting covariate balance met prespecified targets. Conclusions : In this target trial emulation of AMI patients requiring IMV, early initiation of dexmedetomidine within 24 hours was associated with lower 90‑day mortality and more ventilator‑free days. Findings were robust across multiple causal estimators and cohort restrictions but remain observational. Prospective studies are warranted to confirm causality, define safety boundaries, and guide patient selection.