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

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

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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 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

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

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

In: Circulation, Vol. 116, No. 23, 12.2007, p. 2726-2733.

Research output: Contribution to journalArticle

Raichlin, Eugenia ; Bae, Jang Ho ; Khalpey, Zain ; Edwards, Brooks Sayre ; Kremers, Walter K ; Clavell, Alfredo L. ; Rodeheffer, Richard J. ; Frantz, Robert ; 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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title = "Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation",
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.",
keywords = "Coronary disease, Immune system, Transplantation",
author = "Eugenia Raichlin and Bae, {Jang Ho} and Zain Khalpey and Edwards, {Brooks Sayre} and Kremers, {Walter K} and Clavell, {Alfredo L.} and Rodeheffer, {Richard J.} and Robert Frantz and Charanjit Rihal and Amir Lerman and Kushwaha, {Sudhir S.}",
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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 Sayre

AU - Kremers, Walter K

AU - Clavell, Alfredo L.

AU - Rodeheffer, Richard J.

AU - Frantz, Robert

AU - Rihal, Charanjit

AU - Lerman, Amir

AU - Kushwaha, Sudhir S.

PY - 2007/12

Y1 - 2007/12

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

DO - 10.1161/CIRCULATIONAHA.107.692996

M3 - Article

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VL - 116

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JO - Circulation

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