BIOLOGIC AND THERAPEUTIC ADVANCES IN HEART TRANSPLANTATION I

M.J. Barten¹, J.M. Arizon², G. Dong³, H. Eisen⁴, J. Kobashigawa⁵, H.B. Lehmkuhl⁶, C. Pellegrini⁷, H. Ross⁸, A. Zuckermann^9
1Cardiac Surgery, University Leipzig, Heart Center, Leipzig/GERMANY, ²Unidad De Transplante Cardiaco, Hospital Reina Sofía, Cordoba/SPAIN, ³, Novartis Pharmaceuticals Corporation, East Hanover/UNITED STATES OF AMERICA, ⁴The Center For Advanced Heart Failure Care At Hahnemann, Drexel University, Philadelphia/PA/UNITED STATES OF AMERICA, ⁵Cedars-sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles/CA/UNITED STATES OF AMERICA, ⁶, Deutsches Herzzentrum Berlin, Berlin/GERMANY, ⁷Fondazione Irccs Policlinico 'san Matteo', Universita degli Studi di Pavia, Pavia/ITALY, ⁸, University Health Network, Toronto/CANADA, ⁹Dept. Of Cardiothoracic Surgery, Medical University of Vienna, Vienna/AUSTRIA

Body: Introduction: The use of the mTOR inhibitors sirolimus and everolimus (EVR) in heart transplant recipients (HTxR) offers effective immunosuppression but the antiproliferative mode of action might increase the risk for surgical wound complications. For sirolimus an incidence of 35% was reported for deep surgical wound healing complications in HTxR. Thus, the analysis of incidence and management of wound complications with EVR is of interest. Methods: A post-hoc analysis identified wound complications in the adverse event (AE) databases of 3 randomized multicenter studies in 1007 de novo HTxR: B253 (n=634), A2403 (n=199), A2411 (n=174). HTxR received fixed-dose (EVR 1.5 mg, 3 mg) or TDM-EVR (C0 targeted 3-8 ng/mL), azathioprine (AZA) or mycophenolate mofetil (MMF) with standard- or reduced-exposure cyclosporine A (CsA). Treatment was initiated within the first 72 hours post-Tx. Wound complication AEs up to Day 90 in the pooled EVR group were analyzed overall and per wound complication category for incidence, time to onset, and action taken and compared to AZA and MMF groups. Results: Baseline characteristics were balanced across the three studies. Wound complications occurred overall in 14.8% of EVR-treated HTxR compared to 13.1% with AZA and 8.4% with MMF. Wound and sternal dehiscence occurred in less than 2.0% of HTxR in all groups. The majority of events were wound infections which were classified to their site as incisional, mediastinal or other (Table). In 3.7% of EVR-treated patients, 4.2% of AZA-, and 2.4% of MMF-treated patients the wound complication required no action. Co-medication or non-drug therapy was initiated in 9.7%, 8.9%, 7.2% and 7.3%, 4.2%, and 4.8% of patients in the EVR, AZA, and MMF groups, respectively. Hospitalization for treatment was reported in 7.0% of patients with EVR compared to 5.2% in the AZA and 2.4% in the MMF group. Wound complication events occurred in the first 30 days post-Tx in 10.3%, 11.0%, and 7.2% of patients treated with EVR, AZA, or MMF, respectively. HTxR with initiation of EVR within 24 hours post-Tx had a higher incidence of wound complications than HTxR who started EVR treatment 48-72 hours post-Tx (24.3% versus 12.7%). Conclusion: Our cross-study analysis of 1007 HTxR showed a notably lower incidence of wound complications in HTxR treated with EVR compared to previous reports with sirolimus. The majority of wound complications occurred in the early post-operative phase and did not require or prolong hospitalization. Delaying the initiation of EVR to 48-72 hours post-Tx might help to reduce the risk of wound complications.

Disclosure: All authors have declared no conflicts of interest.