Efficacy and Safety of Bivalirudin Versus Heparin Anticoagulation Therapy for Extracorporeal Membrane Oxygenation: Meta-Analysis

Background We aimed to compare the efficacy and safety of bivalirudin versus heparin as the anticoagulant in patients undergoing Extracorporeal Membrane Oxygenation (ECMO). Methods We conducted a search in PubMed, Embase and the Cochrane Library for all the studies in which bivalirudin was compared to heparin as the anticoagulant for ECMO. Efficacy outcomes were defined as the time to reach therapeutic levels, time within therapeutic range (TTR), thrombotic events, circuit thrombosis, circuit exchanges. Safety outcomes were reported as Heparin-Induced Thrombocytopenia (HIT), major bleeding events, minor bleeding events. Other outcomes included hospital length of stay (LOS), ICU LOS, mortality, 30-day mortality and in-hospital mortality. Results Ten studies were included, involving 1091 patients (Bivalirudin was administered in 405 patients while 686 patients were treated with heparin). A significant reduction in thrombotic events [OR 0.51, 95%CI 0.36,0.73, p =0.0002, I 2 =0%], major bleeding events [OR 0.31, 95%CI 0.10,0.92, p =0.04, I 2 =75%] and in-hospital mortality [OR 0.63, 95%CI 0.44,0.89, p =0.009, I 2 =0%] treated with bivalirudin were found compared with heparin. There were no significant differences between groups regarding the time to reach therapeutic levels[MD 3.53, 95%CI -4.02,11.09, p =0.36, I 2 =49%], TTR[MD 8.64, 95%CI -1.72,18.65, p =0.10, I 2 =77%], circuit exchanges[OR 0.92, 95%CI 0.27,3.12, p =0.90, I 2 =38%], Heparin-Induced Thrombocytopenia (HIT)[OR 0.25, 95%CI 0.02,2.52, p =0.24, I 2 =0%], minor bleeding events[OR 0.93, 95%CI 0.38,2.29, p =0.87, I 2 =0%], hospital LOS[MD -2.93, 95%CI -9.01,3.15, p =0.34, I 2 =45%], ICU LOS[MD -4.22, 95%CI -10.07,1.62, p =0.16, I 2 =0%], mortality[OR 1.84, 95%CI 0.58,5.85, p =0.30, I 2 =60%] and 30-day mortality[OR 0.75, 95%CI 0.38,1.48, p =0.41, I 2 =0%]. The benefit of bivalirudin over heparin was not significant for patients undergoing ECMO for major bleeding events while ruling out the Rivosecchi’s study (OR 0.44, 95%CI 0.71-1.14). Subgroup analysis by patient’s type revealed that studies in children generated lower rate of thrombotic events and major bleeding events compared with adults. Conclusion Our meta-analysis suggests that bivalirudin use as the anticoagulant for ECMO are associated with lower thrombotic events, major bleeding events and in-hospital mortality. Meanwhile, the differences are more pronounced in children than adults. However, the results should be interpreted with caution and further larger, randomized trials are needed to confirm the results.