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

[摘要] 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(3)/mm, P = 0.004; and 6 +/- 8%, P = 0.0001) but not in the SRL group (0.1 +/- 1.13 mm(3)/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(3)/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(3)/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(3)/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.

[关键词] CORONARY-ARTERY-DISEASE;WOUND-HEALING COMPLICATIONS;MYCOPHENOLATE-MOFETIL;HEART-TRANSPLANTATION;INDUCED HYPERTENSION;INTIMAL HYPERPLASIA;NITRIC-OXIDE;RISK-FACTORS;CYCLOSPORINE;RAPAMYCIN