Importance The role of anticoagulant therapy as an adjuvant treatment for sepsis remains controversial. Although observational studies have often suggested benefits, large-scale randomized controlled trials have yielded conflicting results, and the risk-to-benefit profile across different anticoagulant agents remains unclear. Objective To evaluate the efficacy and safety of anticoagulant therapy and its effect on all-cause mortality and major bleeding events in adult patients with sepsis as well as explore differences between study designs and anticoagulant types. Data sources: A systematic search was conducted in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases from inception to 7 August 2025. Study selection: Randomized controlled trials and observational studies comparing any systemic anticoagulant therapy with placebo or standard care in adult patients with sepsis or septic shock were included. Data extraction and synthesis: Two reviewers independently extracted data and assessed the risk of bias. The primary outcomes were all-cause mortality and major bleeding events. Data were pooled using a random-effects model, and results were reported as relative risk with 95% confidence intervals. Main outcomes and results: In total, 10 studies (8 randomized controlled trials and 2 observational studies) involving 7480 patients were included. In the primary analysis of eight randomized controlled trials, anticoagulant therapy was not associated with a significant reduction in all-cause mortality (relative risk, 0.96; 95% confidence interval, 0.78–1.18; I 2 = 50.9%). Conversely, anticoagulant therapy was associated with a nonsignificant trend toward an increased risk of major bleeding (relative risk, 1.19; 95% confidence interval, 0.85–1.66; I 2 = 13.5%). Subgroup analyses revealed significant differences between randomized controlled trials and observational studies ( p = 0.018) and suggested potential differences in efficacy among anticoagulant types ( p = 0.10). Conclusions and relevance: In this systematic review and meta-analysis, anticoagulant therapy did not significantly reduce mortality in a broad population of patients with sepsis and may increase the risk of bleeding. The routine use of anticoagulants in unselected septic patients is not supported. Future research should focus on specific agents such as heparin in well-defined, high-risk patient subgroups. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO registration number: CRD420251123750).
Lu et al. (Thu,) studied this question.