Assessment of the adverse effects of sirolimus versus everolimus in pediatric heart transplant recipients

Abstract

Background Literature is limited comparing adverse effects (AEs) of the proliferation signal inhibitors (PSIs) sirolimus (SRL) and everolimus (EVL) in pediatric heart transplant (HTx) recipients. Methods Single‐center, observational cohort analysis assessing first use of SRL or EVL in pediatric HTx recipients <21 years of age with up to 2 years follow‐up between 2009 and 2020. Results Eighty‐seven patients were included, with 52 (59.8%) receiving EVL and 35 (40.2%) receiving SRL. Tacrolimus with PSI was the most common regimen. Intergroup comparison revealed lower baseline estimated glomerular filtration rate (eGFR) and greater increase in eGFR from baseline to 6 months and latest follow‐up in SRL cohort compared to EVL cohort. There was greater increase in HDL cholesterol in SRL cohort compared to EVL cohort. Intragroup analysis revealed eGFR and HDL cholesterol increased significantly within SRL cohort, triglycerides and glycosylated hemoglobin increased in EVL cohort, and LDL cholesterol and total cholesterol increased in both cohorts (all p < .05). There were no differences in hematological indices or rates of aphthous ulcers, effusions, or infections between cohorts. Incidence of proteinuria was not significantly different among those screened within cohorts. Of those included in our analysis, one patient in SRL cohort (2.9%) and two in EVL cohort (3.8%) had PSI withdrawn due to AE. Conclusion Low‐dose PSIs in calcineurin inhibitor minimization regimens appear well‐tolerated with low withdrawal rate secondary to AE in pediatric HTx recipients. While incidence of most AE was similar between PSI, our results suggest EVL may be associated with less favorable metabolic impact than SRL in this population.

mTor‐inhibition within the first days after pediatric heart transplantation is a potentially safe option to prevent cardiac allograft vasculopathy

“…Every fifth child presented hyperlipidemia in our cohort. The incidences of hyperlipidemia in our study participants are similar (if not lower than in previous studies), a potentially relevant finding given that hyperlipidemia is considered a frequent side effect of therapy with mTor inhibitors 32 …”

“…29,30 The adult Schedule study's long-term results showed that patients randomized to everolimus and low-dose CNI followed by CNI-free therapy maintained significantly better long-term kidney function and significantly less CAV than patients randomized to standard CNI treatment. 31 Considering that CNI-related kidney injury is dose-dependent, and early high exposure may be associated with more severely deteriorating renal function persisting with dose reduction, 30,32 initiating everolimus therapy early permits lower CsA doses from the beginning.…”