Reduction of cyclosporine following the introduction of everolimus in maintenance heart transplant recipients: a pilot study.

Data are scarce concerning the calcineurin inhibitor dose reduction required following introduction of everolimus in maintenance heart transplant recipients to maintain stable renal function. In a 48-week, multicenter, single-arm pilot study in heart transplant patients >12 months post-transplant, everolimus was started at 1.5 mg/day (subsequently adjusted to target C(0) 5-10 ng/ml). Mycophenolate mofetil or azathioprine was discontinued on the same day and cyclosporine (CsA) dose was reduced by 25%, with a further 25% reduction each time calculated glomerular filtration rate (cGFR) decreased to <75% of baseline. Of 36 patients enrolled, 25 were receiving everolimus at week 48. From baseline to week 48, there was a mean decrease of 44.5%, 50.9% and 44.6% in CsA dose, C(0) and C(2), respectively. Mean cGFR was 68.9 +/- 14.5 ml/min at baseline and 61.6 +/- 11.5 ml/min at week 48 (P = 0.018). The prespecified criterion for stable renal function was met, i.e. a mean decrease <or=25% of cGFR from baseline. Two patients experienced biopsy-proven acute rejection Grade 3A (5.6%). Between baseline and week 48, there were significant increases in total cholesterol, LDL cholesterol and triglycerides, and small but significant elevations in liver enzymes. This 1-year pilot study suggests that CsA dose reduction of ca. 40% after initiation of everolimus was associated with a decrease in cGFR, however, based on the prespecified criteria stable renal function was attained.