Sirolimus as primary immunosuppression attenuates allograft vasculopathy with improved late survival and decreased cardiac events after cardiac transplantation.
BACKGROUND
We retrospectively analyzed the potential of sirolimus as a primary immunosuppressant in the long-term attenuation of cardiac allograft vasculopathy progression and the effects on cardiac-related morbidity and mortality.


RESULTS
Forty-five cardiac transplant recipients were converted to sirolimus 1.2 years (0.2, 4.0) after transplantation with complete calcineurin inhibitor withdrawal. Fifty-eight control subjects 2.0 years (0.2, 6.5 years) from transplantation were maintained on calcineurin inhibitors. Age, sex, ejection fraction, and time from transplantation to baseline intravascular ultrasound study were not different (P>0.2 for all) between the groups; neither were secondary immunosuppressants and use of steroids. Three-dimensional intravascular ultrasound studies were performed at baseline and 3.1 years (1.3, 4.6 years) later. Plaque index progression (plaque volume/vessel volume) was attenuated in the sirolimus group (0.7±10.5% versus 9.3±10.8%; P=0.0003) owing to reduced plaque volume in patients converted to sirolimus early (<2 years) after transplantation (P=0.05) and improved positive vascular remodeling (P=0.01) in patients analyzed late (>2 years) after transplantation. Outcome analysis in 160 consecutive patients maintained on 1 therapy was performed regardless of performance of intravascular ultrasound examinations. Five-year survival was improved with sirolimus (97.4±1.8% versus 81.8±4.9%; P=0.006), as was freedom from cardiac-related events (93.6±3.2% versus 76.9±5.5%; P=0.002).


CONCLUSIONS
Substituting calcineurin inhibitor with sirolimus as primary immunosuppressant attenuates long-term cardiac allograft vasculopathy progression and may improve long-term allograft survival owing 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 are required.
Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Yan
Y
Topilsky
Tal
T
Hasin
Eugenia
E
Raichlin
Barry A
BA
Boilson
John A
JA
Schirger
Naveen L
NL
Pereira
Brooks S
BS
Edwards
Alfredo L
AL
Clavell
Richard J
RJ
Rodeheffer
Robert P
RP
Frantz
Simon
S
Maltais
Soon J
SJ
Park
Richard C
RC
Daly
Amir
A
Lerman
Sudhir S
SS
Kushwaha
D000328:Adult; D019703:Calcineurin / Q000627:therapeutic use; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D016027:Heart Transplantation / Q000401:mortality*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control*; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional; D014652:Vascular Diseases / Q000000981:diagnostic imaging / Q000517:prevention & control*
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D019703:Calcineurin; D020123:Sirolimus