Cardiac allograft vasculopathy (CAV) is the primary cause of late morbidity and mortality in heart transplant patients and remains a major challenge to further improvements in long-term graft survival in this population. Clearly, there is a need for immunosuppressive regimens that reduce the risk of CAV. Certican (everolimus) is a proliferation signal inhibitor developed for the prevention of acute and chronic rejection after solid-organ transplantation. Pre-clinical studies suggest that everolimus prevents vascular remodeling and neointimal proliferation, which are key components of CAV. In a pivotal trial in heart transplantation, everolimus at 1.5 or 3.0 mg plus standard-dose cyclosporine (CsA; Neoral) and corticosteroids demonstrated superior efficacy to azathioprine (AZA) by decreasing the incidence of biopsy-proven acute rejection (BPAR) and the composite end-point, efficacy failure. Importantly, in this trial, everolimus was also associated with a significant reduction in both the incidence and severity of CAV in recipients of heart transplants. Furthermore, cytomegalovirus (CMV) infection rates were significantly lower with everolimus than with AZA. The study suggests that everolimus has the ability to target the primary causes of chronic allograft dysfunction by reducing acute rejection and CMV infection, and preventing CAV. Moreover, these findings indicate that use of everolimus as part of the primary immunosuppression regimen, could provide a major benefit for heart transplant patients, offering a real hope of alleviating CAV in the long term. Few large-scale trials have been conducted in heart transplant patients, so their value must therefore be maximized with findings being effectively translated into clinical practice.
View details for DOI 10.1016/j.healun.2005.01.013
View details for Web of Science ID 000228015300002
View details for PubMedID 15774320