Efficacy and safety of anticoagulant therapy in three specific populations with sepsis: a meta-analysis of randomized controlled trials.

UNLABELLED: 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. 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. CONCLUSION: 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.

Recombinant human soluble thrombomodulin in severe sepsis: a systematic review and meta-analysis.

BACKGROUND: Although recombinant human soluble thrombomodulin (rhTM) is a widely used novel anticoagulant agent for disseminated intravascular coagulation (DIC) in Japan, its clinical efficacy in sepsis-induced DIC has not been demonstrated convincingly. OBJECTIVE: To assess the benefits and harms of rhTM in sepsis-induced DIC patients. METHODS: We conducted a systematic review and meta-analysis of rhTM therapy for sepsis-induced DIC for both randomized controlled trials (RCTs) and observational studies (retrospective case-control studies and/or prospective cohort studies) separately. All-cause mortality (28-30 days) as efficacy and serious bleeding complications as adverse effect were measured as primary outcomes. We assessed body of evidence quality at the outcome level by using the Grading of Evidence, Assessment, Development and Evaluation (GRADE) approach. RESULTS: We analyzed 12 studies (838 patients/3 RCTs; 571 patients/9 observational studies). Pooled relative risk was 0.81 (95% CI, 0.62-1.06) in the RCTs, indicating non-significant reduction in mortality, and 0.59 (95% CI, 0.45-0.77) in the observational studies. Meta-regression analysis revealed a significant negative slope between effect size of rhTM therapy and baseline mortality rate in individual studies (P = 0.012), suggesting that probability of a beneficial effect with rhTM therapy increases with increasing baseline risk. Risk of serious bleeding complications was not significantly different between rhTM and control groups. We judged the quality of evidence as moderate for mortality and serious bleeding. CONCLUSIONS: The rhTM was associated with a trend in reduction of mortality at 28-30 days in sepsis-induced DIC patients. Further large rigorous trials are needed to confirm or refute these findings before implications for practice are clear.

Meta-analysis: the risk of venous thromboembolism in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a systemic disorder that predominantly affects the bowels but is also associated with venous thromboembolism (VTE). AIM: To provide a quantitative assessment of the association of IBD with venous thromboembolism risk and to explore the possible sources of heterogeneity in the current literature, a meta-analysis of case-control and cohort studies was conducted. METHODS: Studies were identified by a literature search of the PubMed and Scopus databases (from inception inclusive 31 December 2012) for English language studies. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with fixed- and random-effects models. Several subgroup analyses were performed to explore potential study heterogeneity and bias. RESULTS: Eleven studies met our inclusion criteria. The summary RR for deep venous thromboembolism (DVT) and pulmonary embolism (PE) comparing subjects both with and without IBD was 2.20 (95% CI 1.83-2.65). After adjusting for obesity and smoking, summary relative risks near 2.0 were seen for venous thromboembolism in both UC and CD patients. CONCLUSION: This meta-analysis showed that inflammatory bowel disease is associated with an approximately two-fold increase in the risk of venous thromboembolism.