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

Min Ma; Shichu Liang; Jingbo Zhu; Manyu Dai; Zhuoran Jia; He Huang; Yong He

doi:10.3389/fphar.2022.771563

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

Front Pharmacol. 2022 Apr 14:13:771563. doi: 10.3389/fphar.2022.771563. eCollection 2022.

Authors

Min Ma^{1

2}, Shichu Liang¹, Jingbo Zhu³, Manyu Dai⁴, Zhuoran Jia⁴, He Huang¹, Yong He¹

Affiliations

¹ Department of Cardiology, West China Hospital of Sichuan University, Chengdu, China.
² Department of Cardiology, The Sixth People's Hospital of Chengdu, Chengdu, China.
³ Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

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 (I ² = 48%, p = 0.01, odd ratio (OR) = 0.17, 95% confidence interval (CI): 0.04-0.66), patient thrombosis (I ² = 0%, p = 0.02, OR = 0.58, 95% CI: 0.37-0.93), in-circuit thrombosis/interventions (I ² = 0%, p = 0.0005, OR = 0.40, 95% CI: 0.24-0.68), and in-hospital mortality (I ² = 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 (I ² = 48%, p = 0.65, OR = 0.87, 95% CI: 0.46-1.62), 30-day mortality (I ² = 0%, p = 0.61, OR = 0.83, 95% CI: 0.41-1.68), and ECMO duration in adults (I ² = 41%, p = 0.75, mean difference (MD) = -3.19, 95% CI: -23.01-16.63) and children (I ² = 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.

Keywords: bivalirudin; extracorporeal membrane oxygenation; heparin; meta-analysis; systematic review.