Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation

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

Research output: Contribution to journalArticle

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Abstract

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

Original languageEnglish (US)
Pages (from-to)2726-2733
Number of pages8
JournalCirculation
Volume116
Issue number23
DOIs
StatePublished - Dec 1 2007

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Sirolimus
Heart Transplantation
Immunosuppression
Allografts
Transplantation
Azathioprine
Immunosuppressive Agents
Calcineurin Inhibitors
Steroids

Keywords

  • Coronary disease
  • Immune system
  • Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Raichlin, E., Bae, J. H., Khalpey, Z., Edwards, B. S., Kremers, W. K., Clavell, A. L., ... Kushwaha, S. S. (2007). Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation. Circulation, 116(23), 2726-2733. https://doi.org/10.1161/CIRCULATIONAHA.107.692996

Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation. / Raichlin, Eugenia; Bae, Jang Ho; Khalpey, Zain; Edwards, Brooks S.; Kremers, Walter K.; Clavell, Alfredo L.; Rodeheffer, Richard J.; Frantz, Robert P.; Rihal, Charanjit; Lerman, Amir; Kushwaha, Sudhir S.

In: Circulation, Vol. 116, No. 23, 01.12.2007, p. 2726-2733.

Research output: Contribution to journalArticle

Raichlin, E, Bae, JH, Khalpey, Z, Edwards, BS, Kremers, WK, Clavell, AL, Rodeheffer, RJ, Frantz, RP, Rihal, C, Lerman, A & Kushwaha, SS 2007, 'Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation', Circulation, vol. 116, no. 23, pp. 2726-2733. https://doi.org/10.1161/CIRCULATIONAHA.107.692996
Raichlin, Eugenia ; Bae, Jang Ho ; Khalpey, Zain ; Edwards, Brooks S. ; Kremers, Walter K. ; Clavell, Alfredo L. ; Rodeheffer, Richard J. ; Frantz, Robert P. ; Rihal, Charanjit ; Lerman, Amir ; Kushwaha, Sudhir S. / Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation. In: Circulation. 2007 ; Vol. 116, No. 23. pp. 2726-2733.
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abstract = "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 mm/mm, P=0.004; and 6±8{\%}, P=0.0001) but not in the SRL group (0.1±1.13 mm/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/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/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/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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TY - JOUR

T1 - Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation

AU - Raichlin, Eugenia

AU - Bae, Jang Ho

AU - Khalpey, Zain

AU - Edwards, Brooks S.

AU - Kremers, Walter K.

AU - Clavell, Alfredo L.

AU - Rodeheffer, Richard J.

AU - Frantz, Robert P.

AU - Rihal, Charanjit

AU - Lerman, Amir

AU - Kushwaha, Sudhir S.

PY - 2007/12/1

Y1 - 2007/12/1

N2 - 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 mm/mm, P=0.004; and 6±8%, P=0.0001) but not in the SRL group (0.1±1.13 mm/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/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/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/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.

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

KW - Coronary disease

KW - Immune system

KW - Transplantation

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U2 - 10.1161/CIRCULATIONAHA.107.692996

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