The study was designed to target the impact of everolimus on certain complications such as acute rejection and cardiac allograft vasculopathy (also known as chronic rejection), the thickening of the innermost wall of the transplanted heart's coronary arteries, which can restrict blood supply and place the patient's life at risk.
"After one year post-transplant, cardiac allograft vasculopathy is the most serious cause of long-term complications and death," says lead investigator Howard Eisen, M.D., Director, Advanced Heart Failure Center at Temple University Hospital and School of Medicine. "It is the major reason why many transplant patients do not survive long term. The impressive ability of everolimus to decrease the incidence and severity of cardiac allograft vasculopathy could offer transplant patients a powerful tool to improve long-term survival--one of the major challenges in transplantation. Further, everolimus reduced the rate of acute rejection, a major problem for these patients in the first year after transplant."
More than 600 cardiac transplantation patients enrolled in the study at 52 medical centers in the United States, Canada, Europe and South America, making it one of the largest study enrollments in this patient population. More than 2,000 heart transplants are performed in the United States each year, according to the United Network for Organ Sharing (UNOS).
Researchers also reported that everolimus significantly reduced the incidence of cytomegalovirus (CMV) infection, a major infection after transplantation and an important risk factor for the development of cardiac allograft vasculopathy and other problems.
Described as a "proliferation inhibitor," everolimus appears to target many of the underlying causes of cardiac allograft vasculopathy (chronic rejection) in transplantation. The drug was developed by Novartis and has been submitted for regulatory review for use in both kidney and heart transplantation in the USA, Canada and the European Union.
In this 12-month analysis of a two-year international study of 634 heart transplant patients, [all receiving the standard regimen of cyclosporine and steroids in addition to treatment medication], Eisen and his colleagues documented that the regimen with everolimus, given at doses of either 3.0 or 1.5 milligrams per day (mg/d), significantly lowered the incidence of acute rejection episodes, as well as reducing the potential for cardiac allograft vasculopathy and the severity of the disease, when compared to the regimen using azathioprine (1 to 3 mg/kilogram of patient body weight/day).
The study included a novel approach and analysis for defining the presence and severity of cardiac allograft vasculopathy: intravascular ultrasound (IVUS). This technique uses sound waves to visualize the walls of the coronary arteries. The IVUS analysis was developed and conducted by Dr. E. Murat Tuzcu of the Cleveland Clinic Foundation in Ohio.
Eisen's team of investigators included scientists from the Cleveland Clinic Foundation, the Hopital La Pitie Salpetriere in France, University of California at Los Angeles, Columbia Presbyterian Medical Center in New York, Stanford University School of Medicine in California, Skejby University Hospital in Denmark, Deutsches Herzzentrum in Germany and Novartis in East Hanover, NJ, and Basel, Switzerland.
Novartis Pharmaceuticals supported the study.
Temple University Hospital is a 657-bed teaching hospital located on Temple University's Health Sciences Center campus in Philadelphia. The hospital provides a comprehensive array of inpatient and outpatient services to its surrounding community and highly specialized tertiary services to the entire Philadelphia region and beyond. Temple, which has performed heart transplants since 1984, has one of the largest heart transplant programs in the United States. It provides an environment for the highest quality patient care, teaching, training and research while treating 20,000 inpatients and 150,000 outpatients annually. Temple University Hospital is the chief clinical training site for the Temple University School of Medicine.
Notes to Editors:
Journal
New England Journal of Medicine