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.


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.
Raichlin
Eugenia
E
Mayo Clinic (Go 5-469), Rochester, MN 55905, USA.
Bae
Jang-Ho
JH
Khalpey
Zain
Z
Edwards
Brooks S
BS
Kremers
Walter K
WK
Clavell
Alfredo L
AL
Rodeheffer
Richard J
RJ
Frantz
Robert P
RP
Rihal
Charanjit
C
Lerman
Amir
A
Kushwaha
Sudhir S
SS
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000008:administration & dosage; D003327:Coronary Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D020123:Sirolimus / Q000008:administration & dosage*; D014184:Transplantation, Homologous
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine; D020123:Sirolimus