Mycophenolate Mofetil Appears Superior To Azathioprine At Slowing Progression Of Vascular Disease After Heart Transplant

Researchers reported today that patients treated with CellCept® (mycophenolate mofetil), a drug used to prevent rejection in organ transplantation, have significantly lower progression of intimal thickening, or thickening of the inner artery walls, compared with azathioprine (AZA). Intimal thickening is becoming increasingly important as a surrogate marker for long-term outcomes after heart transplantation. The study used intravascular ultrasound (IVUS) to measure intimal thickening in heart transplant patients immediately after surgery and one year later.

“These findings support published registry data that show significantly increased survival rates in CellCept-treated patients at three years,” said Jon A. Kobashigawa, M.D., professor of medicine at the University of California, Los Angeles, Medical Center, and lead investigator of the study.

“Intimal thickening, as measured by IVUS, is a key indicator of vascular disease progression. These important data therefore confirm that heart transplant patients treated with CellCept have significantly less progression of intimal thickening than those treated with AZA. The prospect of achieving better long-term outcomes by slowing the progression of vascular disease is a significant benefit for transplant patients and the surgeons who treat them.”

In the CellCept-treated group, only 23% of patients had an increase in intimal thickness of > 0.3mm versus 43% of patients treated with AZA. Studies have shown that patients with changes in intimal thickening of more than 0.3mm are more likely to have poor outcomes, such as myocardial infarction, organ failure and death.

Presented at the International Society for Heart and Lung Transplantation scientific sessions, the study used a more modern and clinically relevant site-to-site IVUS analysis of heart transplant patients to reanalyze intimal thickness in patients in the pivotal CellCept trial published in 1998.

The antiproliferative and immunosuppressive properties of CellCept appear to slow progression of hyperplasia and reduce damaging immune reactions in the intimal cells.

“IVUS makes it possible to do site-to-site assessment of maximal intimal thickening in the same location in the artery at baseline and at one year,” Dr. Kobashigawa said. “Site-to-site analysis offers greater accuracy in determining increases in intimal thickness compared with morphometric analysis, which averages the thickness of multiple areas of the artery.”

The new IVUS analysis was performed on 196 patients who were part of a 650-patient study at 28 centers. Patients were treated with either CellCept or AZA in addition to cyclosporine and corticosteroids. Since the original study, which found statistically significant improvement in one-year survival rates in CellCept-treated patients compared with AZA-treated patients, ISHLT and UNOS registry studies have shown that CellCept-treated patients have statistically significant improved three-year survival rates as well, compared to AZA-treated patients (91% vs. 86%).

About ISHLT

The International Society for Heart and Lung Transplantation (ISHLT) is a not-for-profit organization dedicated to the advancement of the science and treatment of end-stage heart and lung diseases. Created in 1981 at a gathering of about 15 cardiologists and cardiac surgeons, the Society now includes more than 2,200 members from 45-plus countries, representing a variety of disciplines involved in the management and treatment of end-stage heart and lung disease.

ISHLT maintains two databases. The International Heart and Lung Transplant Registry is a one-of-a-kind registry that has been collecting data since 1983 from 223 hospitals from 18 countries. The ISHLT Mechanical Circulatory Device (MCSD) database has been collecting data since 2002 with the aim of identifying patient populations who may benefit from MCSD implantation; generating predictive models for outcomes; and assessing the mechanical and biological reliability of current and future devices.