Bivalirudin vs. heparin in paediatric and adult patients on extracorporeal membrane oxygenation: A meta‐analysis

Abstract

Aims Unfractionated heparin (UFH) has been the primary anticoagulant of choice on extracorporeal membrane oxygenation (ECMO). However, it is debatable whether bivalirudin (BIV), a direct thrombin inhibitor, may be considered a better alternative anticoagulant option. Methods We searched Embase, Pubmed, Cochrane library, http://Clinicaltrials.gov, CNKI and Wanfang databases up to 15 June 2021. Randomized controlled trials and observational studies were considered eligible for inclusion. Random‐effects meta‐analyses, including subgroup analyses, were conducted. Results A total of 9 studies containing 994 patients were enrolled. All articles were retrospective cohort studies. Compared with UFH, BIV was associated with lower risks of major bleeding (risk ratio [RR]: 0.32, 95% confidence interval [CI] 0.22–0.49), ECMO in‐circuit thrombosis (RR: 0.57, 95% CI 0.43–0.74), stroke (RR: 0.52, 95% CI 0.29–0.95) and in‐hospital mortality (RR: 0.82, 95% CI 0.69–0.99), and higher rates of survival to ECMO decannulation (RR: 1.18, 95% CI 1.03–1.34). Pooled risk estimates did not show a significant association with clinical thrombotic events (RR: 0.69, 95% CI 0.45–1.07). Moreover, BIV was associated with a lower risk of ECMO in‐circuit thrombosis and in‐hospital mortality in the adult subgroup but not in the paediatric subgroup. However, leave‐one‐out sensitivity analyses indicated that the results of stroke, survival to ECMO decannulation and in‐hospital mortality should be interpreted with caution. Conclusion BIV appears to be a potential alternative to UFH in paediatric and adult patients requiring ECMO.

Evaluation of clinical outcomes in patients treated with heparin or direct thrombin inhibitors during extracorporeal membrane oxygenation: a systematic review and meta-analysis

“…Additionally, the use of bivalirudin was associated with reduced major bleeding events (risk ratio: 0.32, 95% confidence interval [CI] 0.22–0.49), reduced incidences of ECMO in-circuit thrombosis (risk ratio: 0.57, 95% CI 0.43–0.74) and stroke (RR: 0.52, 95% CI 0.29–0.95) and higher survival rates until weaning from ECMO (RR: 1.18, 95% CI 1.03–1.34). Of note, the authors performed a „leave-one-out “ sensitivity analysis which showed that the results for in-hospital-mortality, stroke and survival until ECMO weaning should be interpreted carefully and more prospective / good-quality studies are needed [ 13 ].…”

“…To date, three meta-analyses are available that compared bivalirudin and heparin in patients undergoing ECMO while no meta-analysis is available for argatroban [12][13][14]64]. All of the bivalirudin analyses were published in 2022 which clarifies the high relevance of this topic.…”

“…Therefore, some centers primarily use DTI for anticoagulation during ECMO as they might have beneficial influence on outcome [ 11 ]. A meta-analysis recently indicated a survival benefit and a reduced incidence of thrombosis in adults treated with bivalirudin as compared to heparin during ECMO therapy [ 12 , 13 ]. For argatroban, while systematic reviews were conducted, meta-analyses are lacking [ 14 ].…”

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

“…In a cross-sectional survey of 22 Level IV NICUs involved in a neonatal ECMO focus group across the Children’s Hospital Neonatal Consortium from May to July 2022, DiGeronimo and colleagues reported that the 14 centers that incorporated bivalirudin into patient care were found to have fewer bleeding events, longer circuit life, and fewer transfusion of blood products, albeit one site experienced increased circuit complications with bivalirudin ( 35 ). Similarly, in a meta-analysis of nine retrospective studies with 994 adult and pediatric patients, of which five studies included pediatric patients, Mei et al ( 36 ) found significantly lower risks of major bleeding in pediatric patients on bivalirudin versus heparin (RR: 0.27, 95% CI 0.11–0.0.64, p = 0.003). In our review, while only the study by Hamzah et al ( 28 ) reached significance, most studies reported higher rates of bleeding in heparin patients, corroborating prior literature that bivalirudin may be a safer alternative associated with fewer bleeding events.…”

Growing body of evidence supporting the use of Bivalirudin as alternative anticoagulation during extracorporeal membrane oxygenation.

“…We congratulate Li et al for their meta-analysis investigating the value of an alternative strategy of anticoagulation for patients supported by extracorporeal membrane oxygenation (ECMO) 1 . The authors divided the ECMO patients according to the use of unfractionated heparin or bivalirudin.…”