Heparin Therapy and Mortality in Patients with Sepsis: An Observational Study Using a Marginal Structural Cox Model Based on MIMIC-IV Database

Abstract

Abstract Introduction Although heparin has been widely used in clinical practice, its effect on mortality in sepsis is still controversial. This study aimed to investigate the effectiveness of heparin in septic patients. Methods Adult septic patients were identified from the Medical Information Mart for Intensive Care (MIMIC)-IV 2.0 database, which contains patients admitted to intensive care units (ICUs) at the Beth Israel Deaconess Medical Centre from 2008 to 2019. Propensity score matching (PSM) was employed to adjust for the baseline differences in the probability to receive heparin or not. The marginal structural cox model (MSCM) was used to account for both baseline and time-dependent covariates. Group-based trajectory modelling (GBTM) was performed to identify activated partial thromboplastin time (APTT) trajectory groups, and patient outcomes were compared between the heparin- and non-heparin groups in each phenotype. Results A total of 9940 septic patients were enrolled in the study, including 1690 (17%) in the heparin group. By PSM, significant benefit in terms of mortality was observed among the heparin group (HR = 0.82; 95% CI 0.71–0.94; p = 0.004). Similar findings were replicated with the MSCM analysis (HR = 0.66; 95% CI 0.44–0.98; p = 0.038). In the GBTM analysis, three APTT trajectory groups were identified: “normal” (n = 8236; 82.8%); “medium high” (n = 1358; 13.7%); and “high” (n = 346; 13.5%). Heparin therapy was associated with a reduced mortality (HR, 0.59; 95% CI, 0.41–0.84; p = 0.003) in patients with the medium high APTT level [51.7 s (interquartile range, 40.1–64.3)]. Conclusions Heparin therapy was associated with improved outcome in septic patients, and it showed significant survival benefit in patients achieved the medium high APTT phenotype.

Keywords

• Sepsis
• Heparin therapy
• Marginal structural modelling
• Clinical outcome