Cardiac-Allograft Vasculopathy Is Significantly Lower Among Heart Transplant Patients Treated with Everolimus

The severity and incidence of cardiac-allograft vasculopathy was significantly lower among first heart transplant patients treated with everolimus compared with those treated with azathioprine.

“Everolimus combined with cyclosporine and corticosteroids during the first 12 months is a safe and effective immunosuppressant regimen for use in recipients of a first heart transplant,” writes Howard J. Eisen, MD, of Temple University, Philadelphia, Pennsylvania, United States, and colleagues. They conducted a randomised, double-blind comparison of 2 dosages of everolimus or azathioprine, in combination with cyclosporine, corticosteroids, and statins in 634 first heart transplant patients. The primary endpoint was death, graft loss or a second transplantation, loss to follow-up, or biopsy-proven rejection of at least grade 3A or any haemodynamic compromise-associated rejection episode during 6 months post-transplantation, or both.

At 6 months, 46.7% of the 214 patients treated with azathioprine (1.0 to 3.0 mg per kilogram of body weight daily and maximal dose of 300 mg/day) had reached the primary endpoint. Among the 209 patients treated with 1.5 mg everolimus daily, 36.4% reached the primary endpoint, while 27.0% of the 211 patients in the 3.0 mg/day everolimus group had done the same.

At 12 months post-transplantation, the primary endpoint was reached by 52.8% of the azathioprine group, 41.6% of the 1.5 mg everolimus group, and 32.2% of the 3.0 mg everolimus group. The researchers report that the significant reduction in the frequency of rejection of at least grade 3A was the individual variable most responsible for the benefit of everolimus therapy.

Additionally, the everolimus treated patients had a smaller average increase in maximal intimal thickness 12 months post-transplantation, a significantly lower incidence of vasculopathy, and lower rates of cytomegalovirus infection than patients treated with azathioprine. However, patients treated with everolimus had significantly higher levels of serum creatinine and those in the 3.0 mg everolimus group had significantly higher rates of bacterial infection than patients receiving azathioprine.

“Our finding that everolimus significantly reduced the frequency and severity of vasculopathy, as measured by intravascular ultrasonography, offers a note of cautious optimism with respect to the control of this disorder,” Dr. Eisen and colleagues write. To determine the optimal dose and long-term benefits of everolimus for the prevention of vasculopathy, the authors suggest that further follow-up and evaluation are needed.

N Eng J Med 2003;349:847-858.