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1. in the long-term attenuation of cardiac allograft vasculopathy progression and
2. the effects on cardiac-related morbidity and mortality.

METHODS:  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.

RESULTS:  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

1. reduced plaque volume in patients converted to sirolimus early (<2 years) after transplantation (P=0.05) and
2. 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.

1. Five-year survival was improved with sirolimus (97.4±1.8% versus 81.8±4.9%; P=0.006),
2. There 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

1. attenuates long-term cardiac allograft vasculopathy progression and
2. may improve long-term allograft survival owing to favorable coronary remodeling.