Association between inpatient aspirin exposure and 28-day mortality in critically ill patients with sepsis-induced coagulopathy: A cohort study

This study aimed to evaluate the association between inpatient aspirin exposure and 28-day mortality in critically ill patients with sepsis-induced coagulopathy (SIC). We conducted a retrospective cohort study extracting data from the MIMIC-IV v3.1 database (2008-2022). Adult critically ill patients with SIC in the intensive care unit (ICU) were included. The primary outcome was 28-day mortality. Secondary outcomes encompassed mortality (e.g., in-hospital, ICU, 60-day, 90-day, and 1-year) and duration of ICU-free, ventilation-free, or vasopressor-free days within 28 days of admission to the ICU. Multivariable Cox regression, propensity score matching (PSM), inverse probability of treatment weighting (IPTW), overlap weighting (OW), pairwise algorithmic weighting (PA), and doubly robust estimation were employed to control confounders. Robustness of findings was assessed through subgroup and sensitivity analyses. Among 9095 critically ill patients with SIC, 3207 (35.3%) received aspirin during ICU hospitalization. After 1:1 propensity score matching (2069 pairs), inpatient aspirin exposure was independently associated with significantly lower 28-day mortality (hazard ratio [HR] 0.74; 95% confidence interval [CI]: 0.65-0.85; P < .001). This association remained consistent across multiple analytical methods including IPTW (HR 0.76; 95% CI: 0.70-0.84; P < .001), OW (HR 0.72; 95% CI: 0.61-0.84; P < .001), PA (HR 0.73; 95% CI: 0.61-0.84; P < .001), and doubly robust estimation (HR 0.76; 95% CI: 0.61-0.94; P < .001). Inpatient aspirin exposure was also associated with more favorable secondary clinical outcomes (all P < .001). In critically ill patients with SIC, inpatient aspirin exposure was independently associated with lower 28-day mortality and more favorable clinical outcomes. These findings should be interpreted as an association rather than evidence of a causal therapeutic effect. Prospective randomized studies are warranted to validate these findings.