Undue Infection Risk from Proliferation Signal Inhibitors When Initiated Later after Heart Transplantation

Abstract

Purpose Proliferation signal inhibitors (PSIs) have been shown to decrease the incidence of cardiac allograft vasculopathy (CAV) and rejection in clinical trials when given at the time of heart transplantation. These trials have also demonstrated that patients on PSIs have a reduced risk of CMV infection post-transplant. However, the effect of PSIs on overall infection rates when given later post-transplant has not been clearly delineated. We sought to evaluate the incidence of infection post-PSI initiation at our single center. Methods Between 2010 and 2015 we assessed 550 heart transplant patients, 187 of which were initiated on a PSI (sirolimus or everolimus) over a five-year period after heart transplant. Endpoints included subsequent 2-year survival and subsequent 2-year freedom from infection (including CMV). A control population with patients not initiated on a PSI (n=363) was also included. Results 187/550 (34.0%) of heart transplant patients were initiated on a PSI over a five-year period after heart transplant. Patients were initiated on a PSI due to rejection, malignancy, CMV viremia, CAV, circulating antibodies, renal insufficiency and infection. The average time to PSI initiation was 1.3 years. Patients on a PSI compared to patients on no PSI had significantly reduced subsequent 2-year survival and reduced subsequent 2-year freedom from infection (see table). There was no difference in subsequent 2-year freedom from CMV infection. Conclusion PSI initiation later after heart transplant is associated with less than optimal outcomes. However, as PSI is used in high-risk patients, the outcomes are not unexpected but PSI use may have increased infection risk. PSI should be used with caution in these patients.