ABSTRACT
BACKGROUND: Cardiac transplantation, a procedure nearly abandoned in the 1970s, has evolved into the standard of care for appropriate patients with end-stage heart failure. Much of this success has been due to improvements in immunosuppression, including the introduction of a triple-drug regimen. Retrospective reports suggested that single-drug immunosuppression with tacrolimus was feasible. As such, a prospective, randomized trial was conducted to test this approach. METHODS AND RESULTS: One hundred fifty adult de novo heart transplant recipients were enrolled in a prospective, randomized, controlled, open-label trial comparing tacrolimus monotherapy (MONO) with tacrolimus and mycophenolate mofetil therapy (COMBO). Corticosteroids were used in the early postoperative period but discontinued in all patients over 8 to 9 weeks. The primary end point was the composite biopsy score at 6 months after transplant. Patients were followed for 1 to 5 years. The composite biopsy score was similar between groups at 6 and 12 months: 6-month MONO, 0.70 ± 0.44 (95% confidence interval, 0.60 to 0.80) versus COMBO, 0.65 ± 0.40 (95% confidence interval, 0.55 to 0.74; P=0.44). Allograft vasculopathy was assessed by angiography and intravascular ultrasound, with no significant differences noted. Three-year survival was also similar (92.4% MONO versus 97% COMBO; P=0.58, log-rank). CONCLUSIONS: Addition of mycophenolate to single-agent immunosuppression did not provide an advantage over single-agent immunosuppression in terms of rejection, allograft vasculopathy, or 3-year survival. Corticosteroids, which have traditionally been a mainstay of therapy, were successfully discontinued in all patients. These conclusions are tempered by the limited statistical power associated with a sample size of only 150 patients. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00299221.