title: Efficacy and safety of anticoagulant therapy in three specific populations with sepsis: a meta-analysis of randomized controlled trials.
abstract: ESSENTIALS: Most anticoagulant therapy has failed to demonstrate a survival benefit in the overall sepsis population. We conducted separate meta-analyses of anticoagulant therapy in three different populations. Survival benefit was observed only in the septic disseminated intravascular coagulation (DIC) population. Further randomized controlled trials should focus on specific populations with septic DIC.
  
  
  CONCLUSIONS
  
  
  
  BACKGROUND
  Although many preclinical trials have indicated the effectiveness and safety of anticoagulant therapy as an adjuvant therapy against sepsis, there is little evidence to support its effectiveness to reduce mortality in the overall population with sepsis in clinical situations. However, several studies suggested that specific anticoagulant therapy may potentially reduce mortality in patients with sepsis-induced disseminated intravascular coagulation (DIC).
  
  
  OBJECTIVE
  We investigated whether the survival benefit of anticoagulant therapy might pertain to the coagulopathic population with sepsis.
  
  
  METHODS
  We conducted separate meta-analyses of randomized controlled trials for anticoagulant therapy in three different populations: (i) overall population with sepsis, (ii) population with sepsis-induced coagulopathy, and (iii) population with sepsis-induced DIC. We searched MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials comparing anticoagulant therapy with placebo or no intervention in sepsis patients. We measured all-cause mortality as the primary outcome and bleeding complications as the secondary outcome.
  
  
  RESULTS
  We analyzed 24 trials enrolling 14 767 patients. There were no significant reductions in mortality in the overall sepsis population and the population with sepsis-induced coagulopathy. Otherwise, we observed significant reductions in mortality (risk ratio 0.72, 95% confidence interval 0.62-0.85) in the population with sepsis-induced DIC. As adverse events, bleeding complications tended to increase similarly with anticoagulant therapy in all three populations.
  
  
  CONCLUSIONS
  Although associated with an increased risk of bleeding, anticoagulant therapy resulted in no survival benefits in the overall sepsis population and even the population with sepsis-induced coagulopathy; beneficial effects on mortality were observed only in the population with sepsis-induced DIC.
authors.affiliation: Department of Emergency and Critical Care, Osaka General Medical Center, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Umemura
authors.affiliation: Department of Emergency and Critical Care, Osaka General Medical Center, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamakawa
authors.affiliation: Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ogura
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yuhara
authors.affiliation: Department of Emergency and Critical Care, Osaka General Medical Center, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fujimi
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D016009:Chi-Square Distribution; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D018805:Sepsis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants
keywords: anticoagulants; blood coagulation disorders; disseminated intravascular coagulation; meta-analysis; sepsis