A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation: The tacrolimus in combination, tacrolimus alone compared (TICTAC) trial

David A. Baran, Mark J. Zucker, Luis H. Arroyo, Margarita Camacho, Marc E. Goldschmidt, Stephen J. Nicholls, Jeanne Prevost-Fernandez, Candace Carr, Laura Adams, Susan Pardi, Vera Hou, Maria Binetti, Jeanine McCahill, Joanne Chichetti, Valerie Viloria, Mary Gladys SanAgustin, Jennifer Ebuenga-Smith, Leslie Mele, Anthony Martin, Donna BlicharzKathy Wolski, Ludmilla Olesnicky, Fang Qian, Alan L. Gass, Marc Cohen

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39 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)129-137
Number of pages9
JournalCirculation: Heart Failure
Volume4
Issue number2
DOIs
Publication statusPublished - 1 Mar 2011
Externally publishedYes

Keywords

  • Immunosuppression transplantation
  • Intravascular ultrasound
  • Orthotopic heart transplant
  • Randomized controlled trial
  • Transplantation

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