The Efficacy and Safety of Bivalirudin Versus Heparin in the Anticoagulation Therapy of Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis

Abstract

Background: Bivalirudin is a direct thrombin inhibitor (DTI) that can be an alternative to unfractionated heparin (UFH). The efficacy and safety of bivalirudin in anticoagulation therapy in extracorporeal membrane oxygenation (ECMO) remain unknown.Methods: This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A systematic literature search was performed in PubMed, EMBASE, and The Cochrane Library databases to identify all relevant original studies estimating bivalirudin’s efficacy and safety versus UFH as anticoagulation therapy in ECMO. The time limit for searching is from the search beginning to June 2021. Two researchers independently screened the literature, extracted data and evaluated the risk of bias of the included studies. The meta-analysis (CRD42020214713) was performed via the RevMan version 5.3.5 Software and STATA version 15.1 Software.Results: Ten articles with 847 patients were included for the quantitative analysis. Bivalirudin can significantly reduce the incidence of major bleeding in children (I2 = 48%, p = 0.01, odd ratio (OR) = 0.17, 95% confidence interval (CI): 0.04–0.66), patient thrombosis (I2 = 0%, p = 0.02, OR = 0.58, 95% CI: 0.37–0.93), in-circuit thrombosis/interventions (I2 = 0%, p = 0.0005, OR = 0.40, 95% CI: 0.24–0.68), and in-hospital mortality (I2 = 0%, p = 0.007, OR = 0.64, 95% CI: 0.46–0.88). Also, comparable clinical outcomes were observed in the incidence of major bleeding in adults (I2 = 48%, p = 0.65, OR = 0.87, 95% CI: 0.46–1.62), 30-day mortality (I2 = 0%, p = 0.61, OR = 0.83, 95% CI: 0.41–1.68), and ECMO duration in adults (I2 = 41%, p = 0.75, mean difference (MD) = −3.19, 95% CI: −23.01–16.63) and children (I2 = 76%, p = 0.65, MD = 40.33, 95% CI:−135.45–216.12).Conclusions: Compared with UFH, bivalirudin can be a safe and feasible alternative anticoagulant option to UFH as anticoagulation therapy in ECMO, especially for heparin resistance (HR) and heparin-induced thrombocytopenia (HIT) cases.

Heparin-based versus bivalirudin-based anticoagulation in pediatric extracorporeal membrane oxygenation: A systematic review

“…Although most studies in our review did not find a difference in hospital mortality between heparin and bivalirudin groups, existing literature favors fewer events of in-hospital mortality in the aggregate of pediatric and adult patients anticoagulated with bivalirudin compared with heparin. In a systematic review and meta-analysis of ten retrospective studies with a total of 847 adult and pediatric patients, Ma et al ( 12 ) found lower in-hospital mortality in ECMO patients on bivalirudin versus heparin ( I 2 = 0%, p = 0.007, OR = 0.64, 95% CI: 0.46–0.88). However, their analysis of in-hospital mortality combined results of pediatric and adult patients and included only four pediatric studies with a total of 177 pediatric patients.…”

“…This is partially explained by the lower serum levels of AT observed in pediatric patients ( 11 ); however, these differences limit the predictability of heparin’s therapeutic effect. Additionally, patients can become resistant to its anticoagulative effects due to the diminishing amount of AT that heparin binds to and uses for its continued function ( 12 ), which is especially pronounced in children given their lower levels of AT. In addition to these limitations, heparin-induced thrombocytopenia (HIT) is a complication that can also occur when platelets are activated in response to heparin, paradoxically causing thrombosis ( 13 ).…”

ROTEM and Bivalirudin: The Confounding Challenges Ahead

“…e authors concluded that bivalrudin can be a safe and feasible alternative to UFH, especially in the case of HIT and heparin resistance. [7] Anticoagulation monitoring is usually accomplished using aPTT, ACT, plasma drug concentration, anti-IIa assays, or viscoelastic methods. [8] e main disadvantages of these relatively new drugs include direct drug costs, the lack of a specific reversal agent or antidote, and the potential of destabilization of already existing clots.…”

Anticoagulation Strategies during Extracorporeal Membrane Oxygenation: A Narrative Review

“…A recent systematic review and meta-analysis based on 10 articles and 847 patients investigated the efficacy and safety of bivalirudin compared to UFH, revealing that bivalirudin may significantly reduce the incidence of major bleeding (in children) and thrombotic events, in-circuit thrombosis, and in-hospital mortality. The authors concluded that bivalirudin can be a safe and feasible alternative to UFH, especially in the case of HIT and heparin resistance [ 97 ].…”