Major Adverse Cardiovascular Events After Hip Fracture Surgery with Remimazolam or Propofol Total Intravenous Anesthesia: A Retrospective Cohort Study Emulating a Target Trial

BACKGROUND: Remimazolam, a novel short-acting benzodiazepine, is associated with more stable intraoperative hemodynamics than propofol. Older adults undergoing hip fracture surgery represent a vulnerable population at elevated risk for perioperative cardiovascular complications. However, whether remimazolam's hemodynamic advantages translate into reduced major adverse cardiovascular events (MACE) in this population remains uncertain, particularly given recent randomized trials questioning the relationship between intraoperative blood pressure management and postoperative outcomes. We aimed to compare 30-day in-hospital MACE and all-cause in-hospital mortality after general anesthesia with remimazolam versus propofol. METHODS: We conducted a retrospective cohort study using a target trial emulation framework with data from a multicenter Japanese hospital administrative database (September 1, 2020, to September 30, 2024). Eligible participants were adults aged 65 to 99 years undergoing hip fracture surgery who received total intravenous anesthesia with remimazolam or propofol on the day of surgery. The primary outcome was 30-day in-hospital MACE, and the secondary outcome was 30-day all-cause in-hospital mortality. We estimated the average treatment effect among patients who received remimazolam compared with propofol using propensity score weighting. Risks and 95% confidence intervals (CIs) were obtained from weighted cumulative incidence functions with bootstrap resampling. RESULTS: Of 132,422 patients identified, 14,027 were included in the analysis. The primary outcome occurred in 2.86% of the remimazolam group and 2.74% of the propofol group, with no meaningful difference between groups (risk ratio, 1.04 [95% CI, 0.80-1.38]; P = 0.76; risk difference, 0.12% [95% CI, -0.64% to 0.90%]). Thirty-day all-cause in-hospital mortality also did not differ materially between groups (risk ratio, 1.03 [95% CI, 0.61-1.80]; P = 0.91). These findings remained consistent across sensitivity analyses and in subgroup analyses stratified by baseline cardiovascular risk. CONCLUSIONS: Among older adults undergoing hip fracture surgery, 30-day in-hospital MACE and mortality did not differ substantially between remimazolam and propofol, suggesting that anesthetic selection between these agents may not substantially affect short-term cardiovascular outcomes in this high-risk population.