Faculty Collaboration Database

Prevention of acute rejection and allograft vasculopathy by everolimus in cardiac transplants recipients: a 24-month analysis. J Heart Lung Transplant 2007 Jun;26(6):584-92

Date

06/05/2007

Pubmed ID

17543781

DOI

10.1016/j.healun.2007.03.005

Scopus ID

2-s2.0-34249279808 (requires institutional sign-in at Scopus site)   94 Citations

Abstract

BACKGROUND: Everolimus is an immunosuppressive agent that reduces cardiac allograft vasculopathy. This report presents the 24-month results of a multicenter trial of everolimus vs azathioprine in heart transplantation.

METHODS: A total of 634 patients were randomized to receive 1.5 mg everolimus, 3 mg everolimus or azathioprine, with cyclosporine and steroids. A 12-month, double-blind, double-dummy period was followed by a 12-month open-label period.

RESULTS: At 24 months, the percentage of patients reaching the composite efficacy end-points was significantly lower with everolimus (1.5 mg: 45.9%, p = 0.016; 3 mg: 36.0%, p < 0.001) than with azathioprine (57.5%). The change in maximal intimal thickness from baseline to 24 months was significantly smaller with everolimus 1.5 mg (0.07 mm, p = 0.014) and 3 mg (0.06 mm, p = 0.004) compared with azathioprine (0.15 mm). The 24-month incidence of vasculopathy was 33.3% with everolimus 1.5 mg, 45.5% with everolimus 3 mg and 58.3% with azathioprine (p = 0.017 vs everolimus 1.5 mg). Incidence of cytomegalovirus infection was 3-fold lower in patients receiving everolimus compared with azathioprine (7.2% and 7.1% in the 1.5-mg and 3-mg everolimus cohorts, respectively, and 21% in the azathioprine group; p < 0.0001). Median serum creatinine levels at 24 months were higher with everolimus than with azathioprine, but decreased when cyclosporine exposure was reduced (everolimus 1.5 mg: baseline 167 micromol, after 6 months 157.5 micromol; everolimus 3 mg: baseline 185.6 micromol, after 6 months 160 micromol; azathioprine: baseline 123.3 micromol, after 6 months 127 micromol).

CONCLUSIONS: Everolimus significantly reduced acute rejection and limited the progression of allograft vasculopathy at 24 months compared with azathioprine. Although graft and patient survival was comparable at 24 months, everolimus therapy may improve longer-term outcomes after heart transplantation.

Author List

Viganò M, Tuzcu M, Benza R, Boissonnat P, Haverich A, Hill J, Laufer G, Love R, Parameshwar J, Pulpón LA, Renlund D, Abeywickrama K, Cretin N, Starling RC, Eisen HJ, RAD B253 Study Group

MESH terms used to index this publication - Major topics in bold

Adolescent
Adrenal Cortex Hormones
Adult
Aged
Azathioprine
Cyclosporine
Double-Blind Method
Everolimus
Graft Rejection
Heart Transplantation
Humans
Immunosuppressive Agents
Kidney Function Tests
Middle Aged
Safety
Sirolimus
Transplantation, Homologous
Treatment Outcome