EFFICACY AND SAFETY OF APROTININ IN CARDIAC SURGERY: A COMPARISON BETWEEN TWO DOSE REGIMEN (eNAPAR)

Abstract

Objective

Withdrawn in the early 2000s, aprotinin marketing authorization was reinstated by the European Medicine Agency with a restrictive indication (isolated coronary artery bypass grafting, iCABG) and pending a safety registry (NAPaR) intended to record the pattern of use of aprotinin and assess patient safety (1). Despite a ¾ off-label use, it was completed without any safety signal (2). Two different dose regimen were used: full-dose (FD) and half-dose (HD) aprotinin. The objective was to compare both efficacy and safety of each dose regimen in cardiac surgery with cardiopulmonary bypass.

Design and method

Between Feb. 2016 and Aug. 2022, 6,730 adult patients received aprotinin across nine European countries and were included in the registry. To reduce biases and to well balance the probability of receiving each aprotinin dose regimen, we built a propensity score (PS) based on preoperative patients’ characteristics: gender, age, BMI, redo surgery, severe renal impairment, active endocarditis, antiplatelet /anticoagulant agents, emergency surgery, and procedure type (on label/off-label). Then, we performed a regression on the PS-Inverse Probability of Treatment Weighting (IPTW) cohort to analyze the outcomes. The primary outcome was the rate of reoperation for bleeding or tamponade. Three safety outcomes were also investigated: in-hospital mortality, major adverse cardiovascular and cerebral events (MACCE) and renal injury.

Results and conclusions

Among the 6,730 patients, 5,359 had a full set of data allowing building the PS. Reoperation was significantly reduced in FD vs. HD aprotinin, whereas renal injury was slightly increased (Table 1). No difference was found on both mortality and MACCE.

In cardiac surgery with cardiopulmonary bypass, the FD regimen of aprotinin was associated with a decrease in postoperative reoperation for bleeding at the expense of a slight increase in renal injury without any other safety risk. A large multicenter randomized trial is mandatory to consolidate these results.