Napar: efficacy and safety of aprotinin in cardiac surgery: comparison between dose regimen

Introduction Withdrawn in the early 2000s, aprotinin marketing authorization was reinstated by European Medicines Agency with a restrictive indication (isolated coronary artery bypass graft surgery, iCABG) and a safety registry (NAPaR) (1). This regsitry intended to record the pattern of use of aprotinin and to determine patient safety. It was terminated without safety signals associated with the product (2). Two aprotinin regimens were allowed: full-dose (FD) and half-dose (HD). Our objective was to compare efficacy and safety of each regimen in patients undergoing cardiac surgery with cardiopulmonary bypass. Methods Between February 2016 and August 2022, 6730 adult patients were treated with aprotinin across 9 European countries (Germany, Austria, Belgium, France, Ireland, Norway, United Kingdom and Sweden) and were included in the registry Results Among the 1549 patients treated on-label (iCABG), 643 (42%) received the FD regimen and 906 (58%) the HD. Less thromboembolic events (0,5% vs 2,8%; P<0,001) and fibrinogen transfusion, but more platelets and cryoprecipitate were reported in the FD group (Table) . Among the 5181 patients treated off-label (ascending aorta surgery, single or complex valves replacement, transplant), 2318 (45%) received the FD and 2863 (55%) the HD. Less mortality (5,4% vs 9,4%; P<0,001), thromboembolic events (1,4% vs 2,9%; P<0,001), renal events (14,8% vs 18,1%; P=0,002), reoperation for bleeding (5,2% vs 10,3%; P<0,001) and fibrinogen transfusion were reported in the FD group, in association with a rise in transfusion needs (platelets and cryoprecipitate). Discussion Regardless of the surgery, the FD of aprotinin, in comparison with the HD regimen, was associated with less postoperative TEE. Concerning aprotinin use in off-label high bleeding risk surgery, FD regimen was also associated with a decrease in postoperative mortality, reoperation for bleeding and renal dysfunction. To confirm these results, a multivariate analysis will be carried out on propensity-matched sets of HD and FD treated subjects. A large multicenter randomized trial is expected to consolidate the potential benefits of routine use of FD aprotinin in cardiac surgery patients.