Cardiovascular risk factors of sirolimus compared with cyclosporine: early experience from two randomized trials in renal transplantation

Abstract

Introduction: Renal transplant recipients are at a higher risk of cardiovascular events, including death. This paper examines cardiovascular risk factors in two phase II studies comparing cyclosporine (CsA) with sirolimus-based therapy.

Methods: In two phase II studies, patients (n = 161) were randomized at the time of transplantation to receive either sirolimus or CsA in triple-therapy regimens with either azathioprine (Study A) or mycophenolate mofetil (Study B), and corticosteroids. Sirolimus whole blood trough levels were targeted to 30 ng/mL for 2 months and 15 ng/mL thereafter. Pooled results of the two studies are reported.

Results: When patients receiving sirolimus were compared with those receiving CsA, peak cholesterol and trigylcerides at 2 months were markedly and significant higher with sirolimus therapy. The difference between groups decreased thereafter and was not significant from 12 through 24 months. Control of lipid parameters in sirolimus-treated patients was achieved by decreasing the target trough levels after 2 months and by using lipid-lowering agents. Sirolimus-based therapy was associated with a lower incidence of treatment-emergent hypertension (47.5% vs 29.6%, P <.024). At 24 months, the calculated glomerular filtration rate was significantly better with sirolimus (51.3 vs 65.1 mL/min, P <.001). There were no significant differences in the incidences of diabetes or death due to cardiovascular events.

Conclusion: Patients receiving sirolimus experience an initial increase in lipid levels, but these effects are manageable with the use of lipid-lowering agents. Hypertension was less frequent and renal function was improved with CsA-free, sirolimus-based therapy. Based on this early experience, overall cardiovascular risk does not appear to be increased with sirolimus-based compared with CsA-based therapy.