title: Clinical outcome in heart transplant recipients receiving everolimus in combination with dosage reduction of the calcineurin inhibitor cyclosporine A or tacrolimus.
abstract: The mTOR inhibitor everolimus (EVL) can be used for calcineurin inhibitor-sparing immunosuppression in heart transplantation (HTx). However, comparable data regarding clinical outcomes in HTx recipients receiving EVL either with dosage reduction of cyclosporine A (CSA) or with dosage reduction of tacrolimus (TAC) is scarce. In a retrospective data analysis, we compared 5-year clinical outcomes in 154 maintenance patients receiving EVL with CSA (n=106) or TAC (n=48). The primary endpoint was a composite of death, graft loss and EVL discontinuation (treatment failure). Secondary endpoints were kidney function, cardiac rejection, cytomegalovirus infection and biochemical safety parameters. In the CSA and TAC group, the primary endpoint was reached by 59.8% and 53.1%, respectively (P=0.716). Five-year mortality was 30.4% (CSA group) and 23.13% (TAC group), respectively (P=0.371), and freedom from EVL discontinuation was 53.3% and 59.6% (P=0.566) in the respective groups. Covariate-adjusted relative risk of treatment failure was in the CSA group=1.28 (95% CI: 0.70-2.34; P=0.43) compared with the TAC group. The course of covariate-adjusted estimated glomerular filtration rate and freedom from cytomegalovirus infection was similar in the two groups (P=0.502 and P=0.476), whereas covariate-adjusted freedom from rejection was lower in the CSA group compared with the TAC group (P=0.023). Lipid status and blood cell counts were comparable between groups. In conclusion, data indicate that EVL plus reduced TAC is not superior to EVL plus reduced CSA regarding treatment failure and kidney function. However, compared with EVL plus reduced CSA, EVL plus reduced TAC seems to reduce cardiac rejections.
authors.affiliation: Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bad Oeynhausen, Germany. Electronic address: ufuchs@hdz-nrw.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Fuchs
authors.affiliation: Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bad Oeynhausen, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Zittermann
authors.affiliation: Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bad Oeynhausen, Germany.
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Ensminger
authors.affiliation: Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bad Oeynhausen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Schulz
authors.affiliation: Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bad Oeynhausen, Germany.
authors.forename: Jan F
authors.initials: JF
authors.lastname: Gummert
mesh_terms: D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000517:prevention & control; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D016027:Heart Transplantation / Q000401:mortality*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D016559:Tacrolimus
keywords: Cardiac rejection; Everolimus; Heart transplantation; Kidney function; Mortality