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(Circulation. 2007;116:2726-2733.)
© 2007 American Heart Association, Inc.

Transplantation

Conversion to Sirolimus as Primary Immunosuppression Attenuates the Progression of Allograft Vasculopathy After Cardiac Transplantation

Eugenia Raichlin, MD; Jang-Ho Bae, MD; Zain Khalpey, MD, MRCS; Brooks S. Edwards, MD; Walter K. Kremers, PhD; Alfredo L. Clavell, MD; Richard J. Rodeheffer, MD; Robert P. Frantz, MD; Charanjit Rihal, MD; Amir Lerman, MD; Sudhir S. Kushwaha, MD

From the William J. von Liebig Transplant Center and the Division of Cardiovascular Diseases, Center for Coronary Physiology and Imaging, Mayo Clinic, Rochester, Minn.

Correspondence to Sudhir S. Kushwaha, MD, Mayo Clinic (Go 5–469), Rochester, MN 55905. E-mail kushwaha.sudhir{at}mayo.edu

Received January 27, 2007; accepted August 28, 2007.

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 mm³/mm, P=0.004; and 6±8%, P=0.0001) but not in the SRL group (0.1±1.13 mm³/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 mm³/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 mm³/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 mm³/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.

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