Cardiac allograft vasculopathy (CAV): 10-year results of a randomized trial comparing tacrolimus versus cyclosporine in combination with mycophenolate mofetil after heart transplantation

Objectives: Cardiac allograft vasculopathy (CAV) is a major cause of long-term mortality after heart transplantation. Long-term results of prospective randomized trials in this context are scarce.

Methods: 60 consecutive heart transplant recipients included in a prospective randomized trial between 1998 and 2000 combining tacrolimus (TAC) or cyclosporine (CsA) with mycophenolate mofetil (MMF) and steroids (TAC-MMF n=30; CsA-MMF n=30) were examined by routine coronary angiography and analyzed as intention to treat during ten years of study follow-up. Baseline characteristics were well balanced. CAV was graduated in accordance with the new guidelines published by the International Society for Heart and Lung Transplantation.

Results: Freedom from ISHLT≥CAV1at one, five and ten years was 96.4%, 64.0% and 45.8% in TAC-MMF and 88.5% (log-rank 1.2, p=0.281), 34.6% (log-rank 3.0, p=0.085) and 8.0% (log-rank 8.0, p=0.005) in CsA-MMF. The mean time until first diagnosis of CAV was 7.8±0.8 years for TAC-MMF (95% CI 6.2–9.4 years) and 4.6±0.7 years for CsA-MMF (95% CI 3.3–5.9 years). No differences were found for CMV-prophylaxis, rates of coronary angioplasty or stenting, HbA1c-levels or systolic blood pressure after five and ten years. Survival at one, five and ten years was 96.7%, 80.0% and 66.7% for TAC-MMF vs. 90.0%, 83.3% and 80.0% for CsA-MMF (p=ns).

Conclusions: Contrarily to the current opinion, there was a significant difference in manifestation of CAV between TAC-MMF- and CsA-MMF patients in this long-term analysis. Superior freedom from CAV in TAC-MMF patients could be documented only 10 years after HTx did not result in a superior long-term survival.