Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation

BACKGROUND: We investigated the potential of conversion to sirolimus (SRL) as a primary immunosuppressant in attenuating cardiac allograft vasculopathy progression. METHODS AND RESULTS: Twenty-nine cardiac transplant recipients were converted to SRL 3.8±3.4 years after transplantation with complete calcineurin inhibitor (CNI) withdrawal. Secondary immunosuppressants (azathioprine or mycophenolate) and steroids remained unchanged. Forty patients (controls) 4.8±4.0 years from transplantation were maintained on CNIs. Three-dimensional intravascular ultrasound studies were performed at baseline and 12.1±2.6 months later. Mean plaque (media and intima) volume (PV) and plaque index (PI) (PV/vessel volume percent) increased significantly in the CNI group (1.28±2.86 mm/mm, P=0.004; and 6±8%, P=0.0001) but not in the SRL group (0.1±1.13 mm/mm, P=0.63; and 0.1±8%, P=0.94). In patients enrolled within 2 years after transplantation, the increases in PV (0.06±1.06 versus 1.77±1.65 mm/mm; P=0.0081) and PI (0±9% versus 10±8%; P=0.0145) were smaller in the SRL group (n=11) than in the CNI (n=12) group. In patients enrolled ≥2 years after transplantation, the increase in PI was less in the SRL group compared with the CNI group (0.1±6.5% versus 5±8%; P=0.033), but changes in PV did not differ significantly. Treatment with azathioprine or mycophenolate did not affect PV or PI in either the SRL group (PV: 0.22±0.66 versus 0.05±1.45 mm/mm, P=0.46; PI: 1.5±6% versus -1.6±8.5%, P=0.29) or the CNI group (PV: 1.42±1.39 versus 1.06±2.28 mm/mm, P=0.49; PI: 7.8±8.7% versus 4.8±7.3%, P=0.23). CONCLUSIONS: Substituting CNI with SRL as primary immunosuppression attenuates cardiac allograft vasculopathy progression.