Immunosuppressive Therapy in Older Cardiac Transplant Patients

Abstract

Cardiac transplantation has become an established intervention for end-stage heart disease. Clinical outcomes in older cardiac transplant patients have improved over the last decade and are almost similar to those in younger patients. Nevertheless, morbidity and mortality due to infections, cancer and chronic allograft vasculopathy remain problematic. On the other hand, older transplant patients seem to have lower incidences of acute rejection episodes than younger patients. Conventional immunosuppression with calcineurin-inhibiting drugs, azathioprine and corticosteroids is responsible for a number of adverse effects. Although these adverse effects can also be seen in younger patients, tolerance to these agents seems to decrease with increasing age. In particular, diabetes mellitus, osteoporosis and chronic renal insufficiency are associated with higher morbidity and mortality in older cardiac transplant patients. As the elderly become an ever-increasing segment of the cardiac transplant population, new and innovative immunosuppressive strategies will have to be developed and applied.Currently, the availability of new immunosuppressive drugs means more individualised immunosuppressive protocols can be used. New antibodies for induction therapy, a choice between ciclosporin and tacrolimus, and the advent of mycophenolate mofetil as well as proliferation signal inhibitors (everolimus, sirolimus) have changed immunosuppressive protocols dramatically. Therefore, a generalised protocol for all patients has been replaced by individualised immunosuppression depending on the patient group. Moreover, protocols can be modified during follow-up depending on the individual patient's requirements and problems. Hypertension and hyperlipidaemia could be influenced by the selection of tacrolimus over ciclosporin, and weaning of corticosteroids might have a positive impact on osteoporosis or diabetes. There is also no clear evidence that tacrolimus is associated with a higher risk for new onset of diabetes. Chronic renal insufficiency can be managed with calcineurin inhibitor-free immunosuppression consisting of mycophenolate mofetil and proliferation signal inhibitors. Both everolimus and sirolimus also seem to have a protective effect against the onset of graft vasculopathy and some sorts of cancer after cardiac transplantation. As a general rule, however, older cardiac transplant patients should be treated with lower doses and fewer immunosuppressive drugs to avoid over-immunosuppression.