Rejection after conversion to a proliferation signal inhibitor in chronic heart transplantation

Abstract

We sought to determine the incidence, risk factors, and consequences of acute rejection (AR) after conversion from a calcineurin inhibitor (CNI) to a proliferation signal inhibitor (PSI) in maintenance heart transplantation. Relevant clinical data were retrospectively obtained for 284 long-term heart transplant recipients from nine centers in whom CNIs were replaced with a PSI (sirolimus or everolimus) between October 2001 and March 2009. The rejection rate at one yr was 8.3%, stabilizing to 2% per year thereafter. The incidence rate after conversion (4.9 per 100 patient-years) was significantly higher than that observed on CNI therapy in the pre-conversion period (2.2 per 100 patient-years). By multivariate analysis, rejection risk was associated with a history of late AR prior to PSI conversion, early conversion (<5 yr) after transplantation and age <50 yr at the time of conversion. Use of mycophenolate mofetil was a protective factor. Post-conversion rejection did not significantly influence the evolution of left ventricular ejection fraction, renal function, or mortality during further follow-up. Conversion to a CNI-free immunosuppression based on a PSI results in an increased risk of AR. Awareness of the clinical determinants of post-conversion rejection could help to refine the current PSI conversion strategies.

Twelve-month efficacy and safety of the conversion to everolimus in maintenance heart transplant recipients

“…Rejections were observed predominantly in the first 6 mo after conversion and to a similar degree in patients with or without CNI treatment. Recently González-Vílchez et al [36] have shown, in 284 longterm HT recipients, a high rate of acute rejection after conversion from a CNI to mTOR-i in maintenance HT. By multivariate analysis, rejection risk was associated with a history of late AR prior to PSI conversion, early Manito N et al .…”