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WEDNESDAY, Aug. 27, 2003 (HealthDayNews) -- A drug that fights a relatively unpublicized cause of heart transplant failure nearly doubled the success rate in a large-scale trial, researchers report.
Everolimus, a drug still classified as experimental, reduces not only the immune system attack on transplanted tissue but also the overgrowth of cells that can cause failure by blocking blood vessels that feed a transplanted heart, explains trial leader Dr. Howard J. Eisen.
"There are two causes of transplant failure," says Eisen, a professor of medicine and physiology at Temple University School of Medicine. "One is cellular rejection, caused by immune system cells. The other is coronary artery disease, blockage of the arteries that can occur up to a year after a transplant and has been something we have not been able to deal with."
Everolimus "works by inhibiting the proliferation of muscle cells and also proliferation of the immune cells that cause rejection," Eisen says.
In a multi-center trial including more than 600 heart transplant recipients, only 27 percent of patients given a large dose of everolimus suffered death or rejection of the transplant in the first six months after surgery, compared to 46.7 percent of those given azathioprine, a commonly used drug that suppresses the immune system attack, says a report in the Aug. 28 issue of the New England Journal of Medicine.
The failure rate was higher for patients given a smaller dose of everolimus in the trial, 36.4 percent, but that was still well below that of the patients given azathioprine.
Applications for approval of everolimus have already been submitted to the U.S. Food and Drug Administration and European regulatory agencies, Eisen says, and there are hopes for quick approval.
The study was funded in part by Novartis Pharmaceuticals, which makes the drug.
Meanwhile, new studies aimed at improving the results of transplant therapy are being planned, Eisen says. For example, all the patients in the newly reported trial were given standard doses of cyclosporine, another drug designed to blunt the immune attack. New studies will look at the possibility that doses of cyclosporine can be lowered, to reduce side effects.
Studies must also be done to see whether everolimus treatment "can accomplish secondary prevention, to stop or decrease the severity of the disease in people who already have the disease," Eisen says.
A mild note of caution is sounded in an accompanying editorial by Dr. Robin K. Avery, a staff physician in infectious diseases at the Cleveland Clinic Foundation who specializes in transplant infections.
"Whether these early findings will translate into increased longevity and decreased graft loss in future years will be important to confirm," the editorial says.
But in an interview, Avery says that while "you always want to see longer-term results, there is certainly an indication of benefit in this trial that will translate into benefit in the long term."
A variety of treatments have been used to prevent the overgrowth of cells that can choke off transplanted hearts, Avery explains, "but this to my knowledge is the first large randomized trial that shows a difference made by a drug regimen."
More information
The promise and problems of heart transplantation are explained by the National Library of Medicine or the American Heart Association.
