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Previous Volume 349:847-858 August 28, 2003 Number 9 Next

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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.

Source Information

From Temple University, Philadelphia (H.J.E.); the Cleveland Clinic Foundation, Cleveland (E.M.T., R.C.S.); Hôpital La Pitié–Salpêtrière, Paris (R.D.); the University of California at Los Angeles, Los Angeles (J.K.); Columbia Presbyterian Medical Center, New York (D.M.); Stanford University School of Medicine, Stanford, Calif. (H.A.V.-K.); Skejby University Hospital, Aarhus, Denmark (K.S.); Deutsches Herzzentrum, Berlin, Germany (M.H.); Novartis Pharmaceuticals, Summit, N.J. (J.M.L.); and Novartis Pharma, Basel, Switzerland (K.H.A., P.B.).

Address reprint requests to Dr. Eisen at the Section of Cardiology, Temple University School of Medicine, 3401 N. Broad St., Philadelphia, PA 19140, or at eisenh{at}tuhs.temple.edu.

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Everolimus in Cardiac-Transplant Recipients
Banas B., Böger C., Krämer B., Eisen H. J., the RAD B253 Study Group
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N Engl J Med 2003; 349:2271-2272, Dec 4, 2003. Correspondence

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