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Does perioperative use of aprotinin reduce the rejection rate in heart transplant recipients?

Transplant Unit, Papworth Hospital, Papworth Everard, Cambridge, United Kingdom

Received 4 September 2007; received in revised form 22 January 2008; accepted 24 January 2008.

^_* Corresponding author. Address: 6 Grassmount, Taymount Rise, London SE 23 3UW, United Kingdom. Tel.: +44 0208 291 0909. (Email: jeffrey01{at}mac.com).

Objective: Allograft rejection continues to be one of the most common causes of mortality after heart transplantation. We investigated if perioperative use of antifibrinolytics such as aprotinin and tranexamic acid can decrease the rate of rejection after heart transplant and their effect on transfusion. Methods: A retrospective analysis was conducted on the data from patients who received a first heart transplant at Papworth Hospital between 2000 and 2005. Transplant registry and audit data were used for the study. Rejection biopsy results and treatment were used to designate rejection episodes as mild (grades 1A, 1B or 2 untreated) or severe (grades 2 treated, grades 3 and 4). The relationship between antifibrinolytics and rejection episodes was assessed using univariate and multiple Poisson regression. Kaplan–Meier methods and Kruskal–Wallis tests, respectively, were used to analyse survival/time to first rejection and transfusion. Results: There were 225 patients who underwent a first heart transplant between January 2000 and December 2005. Of these, 101 patients (44.9%) had received aprotinin, 63 (28.0%) tranexamic acid, 2 (0.9%) both (aprotinin and tranexamic acid) and 59 (26.2%) no antifibrinolytics. There was no difference in time to first rejection by antifibrinolytic treatment (p = 0.20). There was no difference in the rate of treated rejection per 100 patient-days between aprotinin and tranexamic acid groups between 0 and 3 months post-transplant, (0.6 in both), but aprotinin had a small clinical effect when compared to no treatment (0.6 vs 0.8, p = 0.54). Between 4 and 6 months, the treated and severe rejection rates were lower in the patients receiving aprotinin as compared to those receiving tranexamic acid, but these differences again did not reach statistical significance (0.1 vs 0.3, p = 0.14, 0.2 vs 0.4, p = 0.18). Aprotinin was associated with higher postoperative blood loss and transfusion requirements in the subgroup of patients that had a ventricular assist device, prior sternotomy or anticoagulant therapy. Conclusions: The use of aprotinin in heart transplant surgery may be associated with a small decrease in the incidence of treated/severe rejection within 6 months of transplantation. The perioperative use of antifibrinolytics did not influence time to first rejection or reduce blood transfusion.

Key Words: Heart transplantation • Aprotinin • Rejection