title: Reduction of cyclosporine following the introduction  of everolimus in maintenance heart transplant recipients:  a pilot study.
abstract: 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.
authors.affiliation: Department of Cardiology, Toronto General Hospital, Toronto, ON, Canada. heather.ross@uhn.on.ca
authors.forename: Heather
authors.initials: H
authors.lastname: Ross
authors.forename: Peter
authors.initials: P
authors.lastname: Pflugfelder
authors.forename: Haissam
authors.initials: H
authors.lastname: Haddad
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cantarovich
authors.forename: Michael
authors.initials: M
authors.lastname: White
authors.forename: Andrew
authors.initials: A
authors.lastname: Ignaszewski
authors.forename: Jonathan
authors.initials: J
authors.lastname: Howlett
authors.forename: Marc
authors.initials: M
authors.lastname: Vaillancourt
authors.forename: Richard
authors.initials: R
authors.lastname: Dorent
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Burton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage*; D000068338:Everolimus; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D016027:Heart Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus