The Impact of Proliferation Signal Inhibitors on the Healthcare Burden of Major Adverse Cardiac Events Following Heart Transplantation

Abstract

Cardiac allograft vasculopathy (CAV) is a major burden on the long-term outcome of heart transplantation and is often only diagnosed following the occurrence of major adverse cardiac events (MACE). The proliferation signal inhibitors (PSIs) everolimus and sirolimus are being used with increasing frequency following heart transplantation due to their potent immunosuppressive and antiproliferative effects. In clinical trials in de novo and maintenance heart transplant recipients, PSIs are associated with a reduced incidence of CAV when compared with alternative immunosuppressive regimens. In further analysis of the incidence of MACE at four years post-transplant, everolimus was associated with a lower incidence of MACE in de novo recipients compared with azathioprine. The healthcare burden of these MACE was evaluated through the application of hospitalization costs from the 2003 US Healthcare Cost and Utilization Project. Everolimus treatment was associated with a reduction in the mean cost of MACE per patient in both the intent-to-treat population (57.2% reduction) and a sub-group of patients who underwent intravascular ultrasound examination (60.8% reduction). This model of healthcare cost analysis was subsequently applied to previously published data on the incidence of MACE in maintenance heart transplant recipients following conversion to sirolimus. The average cost of MACE per patient was US $9,117 in sirolimus-treated patients compared with US $37,830 in patients remaining on the original immunosuppressive regimen, a reduction of 75.9%. In conclusion, the antiproliferative benefits of PSI therapy in delaying the progression of CAV are associated with reduced healthcare costs, resulting from MACE in de novo and maintenance heart transplant recipients.