Superiority of Fibrinogen Concentrate Versus Cryoprecipitate for Treatment of Bleeding in Cardiac Surgery Patients: A Secondary Analysis of the FIBRES Randomized Clinical Trial Stratified by Surgical Risk

Objectives: To explore the superiority of fibrinogen concentrate (FC) versus cryoprecipitate for bleeding after cardiac surgery. Design: Secondary analysis of the FIBRES randomized trial. Setting: Eleven Canadian hospitals, February 2017-November 2018. Participants: Adult cardiac surgery patients experiencing significant postbypass bleeding and acquired hypofibrinogenemia (fibrinogen <2.0 g/L or FIBTEM A10 <10 mm). Interventions: FC (4 g) or cryoprecipitate (10 units) dosed within 24 hours after cardiopulmonary bypass as needed. Measurements and Main Results: In total, 735 patients (372 FC, 363 cryoprecipitate) were included in the primary analysis (median age 64 years, 30% women). The primary endpoint was cumulative blood components (red cells, platelets, plasma) administered within 24 hours postbypass. Superiority was assessed using deviance-scaled Poisson regression. FC was superior to cryoprecipitate in the a priori‒defined, well-balanced subgroups of non-critically ill patients (n = 634, 86% of population; mean 13.6 versus 16.2 units, mean ratio 0.84 [95% CI 0.73, 0.96]; p = 0.01) and elective surgery patients (n = 466, 63% of population; 11.7 versus 14.4 units, 0.81 [0.69, 0.96]; p = 0.02). In elective surgery patients, adverse events (relative risk 0.85 [0.75, 0.97]; p = 0.02) and serious adverse events (0.71 [0.52, 0.99]; p = 0.04) were less frequent with FC. Conclusion: FC showed superior hemostatic efficacy to cryoprecipitate in the prespecified subgroups of elective cardiac surgery patients and patients who were not in a critical state before surgery, representing the large majority of patients with bleeding postbypass. FC may also offer safety advantages over cryoprecipitate.