Heart Transplant Patients Benefit From New Approach To Immunosuppression, According To Mayo Clinic

Heart transplant patients are required to take daily immunosuppressive medication to prevent their body from rejecting the transplanted organ. Standard practice has been to treat patients primarily with calcineurin inhibitors. However, calcineurin inhibitors are a major cause of kidney dysfunction and do not prevent transplant coronary artery disease, a rapidly progressing coronary disease that develops in many heart transplant recipients and greatly limits long-term survival.

"Immunosuppression for heart transplant patients using calcineurin inhibitors has been essentially unchanged for 25 years, and the results have not been ideal," says Sudhir Kushwaha, M.D., the lead author and a cardiologist at Mayo Clinic. "Five to 10 years post-transplant, 10 percent of patients are on dialysis or need a kidney transplant. And 10 years post-transplant, 50 percent of patients are either waiting for another heart transplant because of coronary artery disease or have died as a result of it."

Dr. Kushwaha and a team of Mayo Clinic researchers collaborated to study alternative options for immunosuppression, using sirolimus, an anti-proliferative immunosuppression drug with potent anti-rejection properties.

One study involving 78 heart transplant patients over four years found that gradually transitioning stable patients from calcineurin inhibitors to sirolimus showed consistent improvement of kidney function. There was no increase in rejection of the transplanted heart and no difference in heart function.

A second study found gradual transition to sirolimus in 29 patients also greatly impaired the development of the proliferative changes found in transplant coronary artery disease.

"Based on our findings, patients should still receive calcineurin inhibitors as the primary immunosuppressant immediately after transplant, and the conversion to sirolimus must be gradual in order to prevent rejection," says Dr. Kushwaha. "Today, standard practice at Mayo Clinic is to consider converting all heart transplant patients from calcineurin inhibitors to sirolimus at six months post-transplant if there are no contraindications."

Partial funding for this research came from Wyeth Pharmaceuticals. Other researchers participating in the studies include Evgenia Raichlin, M.D.; Brooks Edwards, M.D.; Alfredo Clavell, M.D.; Richard Rodeheffer, M.D.; Robert Frantz, M.D.; Jean Wagner; Richard Daly, M.D.; and Amir Lerman, M.D.

Mayo researchers reported their findings at The International Society for Heart & Lung Transplantation Annual Meeting and Scientific Session in San Francisco.