Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients

Howard J. Eisen, E. Murat Tuzcu, Richard Dorent, Jon Kobashigawa, Donna Mancini, Hannah A. Valantine-Von Kaeppler, Randall C. Starling, Keld Sørensen, Manfred Hummel, Joan M. Lind, Kamal H. Abeywickrama, Peter Bernhardt

Research output: Contribution to journalArticlepeer-review

945 Scopus citations

Abstract

BACKGROUND: Everolimus, a novel proliferation inhibitor and immunosuppressive agent, may suppress cardiac-allograft vasculopathy. We conducted a randomized, double-blind, clinical trial comparing everolimus with azathioprine in recipients of a first heart transplant. METHODS: A total of 634 patients were randomly assigned to receive 1.5 mg of everolimus per day (209 patients), 3.0 mg of everolimus per day (211 patients), or 1.0 to 3.0 mg of azathioprine per kilogram of body weight per day (214 patients), in combination with cyclosporine, corticosteroids, and statins. The primary efficacy end point was a composite of death, graft loss or retransplantation, loss to follow-up, biopsy-proved acute rejection of grade 3A, or rejection with hemodynamic compromise. RESULTS: At six months, the percentage of patients who had reached the primary efficacy end point was significantly smaller in the group given 3.0 mg of everolimus (27.0 percent, P<0.001) and the group given 1.5 mg of everolimus (36.4 percent, P=0.03) than in the azathioprine group (46.7 percent). Intravascular ultrasonography showed that the average increase in maximal intimal thickness 12 months after transplantation was significantly smaller in the two everolimus groups than in the azathioprine group. The incidence of vasculopathy was also significantly lower in the 1.5-mg group (35.7 percent, P=0.045) and the 3.0-mg group (30.4 percent, P=0.01) than in the azathioprine group (52.8 percent). The rates of cytomegalovirus infection were significantly lower in the 1.5-mg group (7.7 percent, P<0.001) and the 3.0-mg group (7.6 percent, P<0.001) than in the azathioprine group (21.5 percent). Rates of bacterial infection were significantly higher in the 3.0-mg group than in the azathioprine group. Serum creatinine levels were also significantly higher in the two everolimus groups than in the azathioprine group. CONCLUSIONS: Everolimus was more efficacious than azathioprine in reducing the severity and incidence of cardiac-allograft vasculopathy, suggesting that everolimus therapy may alleviate this serious problem.

Original languageEnglish (US)
Pages (from-to)847-858
Number of pages12
JournalNew England Journal of Medicine
Volume349
Issue number9
DOIs
StatePublished - Aug 28 2003

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Fingerprint Dive into the research topics of 'Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients'. Together they form a unique fingerprint.

Cite this