Sirolimus as Primary Immunosuppression Attenuates Allograft Vasculopathy with Improved Late Survival and Decreased Cardiac Events Following Cardiac Transplantation
Background—We retrospectively analyzed the potential of Sirolimus (SRL) as primary immunosuppressant in the long-term attenuation of cardiac allograft vasculopathy (CAV) progression and effects on cardiac related morbidity and mortality.
Methods and Results—45 cardiac transplant recipients were converted to SRL 1.2[0.2, 4.0] years after transplantation with complete calcineurin inhibitor (CNI) withdrawal. 58 control subjects 2.0[0.2, 6.5] years from transplantation were maintained on CNIs. Age, sex, ejection fraction and time from transplant to baseline intravascular ultrasound (IVUS) study were not different (P>0.2 for all) between the groups, as well as secondary immunosuppressants and use of steroids. 3D IVUS studies were performed at baseline and 3.1[1.3, 4.6] years later. Plaque index progression (plaque volume/vessel volume) was attenuated in the SRL group (0.7±10.5% vs. 9.3±10.8%, P=0.0003) due to reduced plaque volume in patients converted to SRL early (<2 years) after transplant (p=0.05), and improved positive vascular remodeling (p=0.01) in patients analyzed late after transplant (>2 years). Outcome analysis in 160 consecutive patients, maintained on one therapy was performed irrespective of performance of IVUS exams. Five-year survival was improved with SRL (97.4±1.8 % vs. 81.8±4.9%; p=0.006), as well as the freedom from cardiac related events (93.6±3.2 % vs. 76.9±5.5 %; p=0.002).
Conclusions—Substituting CNI with SRL as primary immunosuppressant attenuates long term CAV progression and may improve long-term allograft survival due to favorable coronary remodeling. Because of the lack of randomization, and retrospective nature of our analysis, the differences in outcome should be interpreted cautiously and prospective clinical trials would be required.
- Received April 26, 2011.
- Accepted December 16, 2011.
- Copyright © 2011, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited