Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients

Rabea Asleh, Alexandros Briasoulis, Walter K Kremers, Rosalyn Adigun, Barry A. Boilson, Naveen Luke Pereira, Brooks Sayre Edwards, Alfredo L. Clavell, John A. Schirger, Richard J. Rodeheffer, Robert Frantz, Lyle D. Joyce, Simon Maltais, John M. Stulak, Richard C. Daly, Jonella Tilford, Woong Gil Choi, Amir Lerman, Sudhir S. Kushwaha

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking. Objectives: The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT. Methods: A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies. Results: The progression in plaque volume (2.8 ± 2.3 mm3/mm vs. 0.46 ± 1.8 mm3/mm; p < 0.0001) and plaque index (plaque volume–to–vessel volume ratio) (12.2 ± 9.6% vs. 1.1 ± 7.9%; p < 0.0001) were significantly attenuated when treated with SRL compared with CNI. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6% of the patients and was lower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95% confidence interval: 0.31 to 0.70; p = 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95% confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (≤2 years) compared with late conversion (>2 years) after HT. Conclusions: Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.

Original languageEnglish (US)
Pages (from-to)636-650
Number of pages15
JournalJournal of the American College of Cardiology
Volume71
Issue number6
DOIs
StatePublished - Feb 13 2018

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Sirolimus
Immunosuppression
Allografts
Heart Transplantation
Transplant Recipients
Calcineurin Inhibitors
Safety
Mortality
Therapeutics

Keywords

  • cardiac allograft vasculopathy
  • coronary intravascular ultrasound
  • heart transplantation
  • immunosuppression

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients. / Asleh, Rabea; Briasoulis, Alexandros; Kremers, Walter K; Adigun, Rosalyn; Boilson, Barry A.; Pereira, Naveen Luke; Edwards, Brooks Sayre; Clavell, Alfredo L.; Schirger, John A.; Rodeheffer, Richard J.; Frantz, Robert; Joyce, Lyle D.; Maltais, Simon; Stulak, John M.; Daly, Richard C.; Tilford, Jonella; Choi, Woong Gil; Lerman, Amir; Kushwaha, Sudhir S.

In: Journal of the American College of Cardiology, Vol. 71, No. 6, 13.02.2018, p. 636-650.

Research output: Contribution to journalArticle

Asleh, R, Briasoulis, A, Kremers, WK, Adigun, R, Boilson, BA, Pereira, NL, Edwards, BS, Clavell, AL, Schirger, JA, Rodeheffer, RJ, Frantz, R, Joyce, LD, Maltais, S, Stulak, JM, Daly, RC, Tilford, J, Choi, WG, Lerman, A & Kushwaha, SS 2018, 'Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients', Journal of the American College of Cardiology, vol. 71, no. 6, pp. 636-650. https://doi.org/10.1016/j.jacc.2017.12.005
Asleh, Rabea ; Briasoulis, Alexandros ; Kremers, Walter K ; Adigun, Rosalyn ; Boilson, Barry A. ; Pereira, Naveen Luke ; Edwards, Brooks Sayre ; Clavell, Alfredo L. ; Schirger, John A. ; Rodeheffer, Richard J. ; Frantz, Robert ; Joyce, Lyle D. ; Maltais, Simon ; Stulak, John M. ; Daly, Richard C. ; Tilford, Jonella ; Choi, Woong Gil ; Lerman, Amir ; Kushwaha, Sudhir S. / Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients. In: Journal of the American College of Cardiology. 2018 ; Vol. 71, No. 6. pp. 636-650.
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abstract = "Background: Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking. Objectives: The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT. Methods: A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies. Results: The progression in plaque volume (2.8 ± 2.3 mm3/mm vs. 0.46 ± 1.8 mm3/mm; p < 0.0001) and plaque index (plaque volume–to–vessel volume ratio) (12.2 ± 9.6{\%} vs. 1.1 ± 7.9{\%}; p < 0.0001) were significantly attenuated when treated with SRL compared with CNI. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6{\%} of the patients and was lower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95{\%} confidence interval: 0.31 to 0.70; p = 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95{\%} confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (≤2 years) compared with late conversion (>2 years) after HT. Conclusions: Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.",
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author = "Rabea Asleh and Alexandros Briasoulis and Kremers, {Walter K} and Rosalyn Adigun and Boilson, {Barry A.} and Pereira, {Naveen Luke} and Edwards, {Brooks Sayre} and Clavell, {Alfredo L.} and Schirger, {John A.} and Rodeheffer, {Richard J.} and Robert Frantz and Joyce, {Lyle D.} and Simon Maltais and Stulak, {John M.} and Daly, {Richard C.} and Jonella Tilford and Choi, {Woong Gil} and Amir Lerman and Kushwaha, {Sudhir S.}",
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T1 - Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients

AU - Asleh, Rabea

AU - Briasoulis, Alexandros

AU - Kremers, Walter K

AU - Adigun, Rosalyn

AU - Boilson, Barry A.

AU - Pereira, Naveen Luke

AU - Edwards, Brooks Sayre

AU - Clavell, Alfredo L.

AU - Schirger, John A.

AU - Rodeheffer, Richard J.

AU - Frantz, Robert

AU - Joyce, Lyle D.

AU - Maltais, Simon

AU - Stulak, John M.

AU - Daly, Richard C.

AU - Tilford, Jonella

AU - Choi, Woong Gil

AU - Lerman, Amir

AU - Kushwaha, Sudhir S.

PY - 2018/2/13

Y1 - 2018/2/13

N2 - Background: Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking. Objectives: The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT. Methods: A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies. Results: The progression in plaque volume (2.8 ± 2.3 mm3/mm vs. 0.46 ± 1.8 mm3/mm; p < 0.0001) and plaque index (plaque volume–to–vessel volume ratio) (12.2 ± 9.6% vs. 1.1 ± 7.9%; p < 0.0001) were significantly attenuated when treated with SRL compared with CNI. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6% of the patients and was lower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95% confidence interval: 0.31 to 0.70; p = 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95% confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (≤2 years) compared with late conversion (>2 years) after HT. Conclusions: Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.

AB - Background: Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking. Objectives: The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT. Methods: A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies. Results: The progression in plaque volume (2.8 ± 2.3 mm3/mm vs. 0.46 ± 1.8 mm3/mm; p < 0.0001) and plaque index (plaque volume–to–vessel volume ratio) (12.2 ± 9.6% vs. 1.1 ± 7.9%; p < 0.0001) were significantly attenuated when treated with SRL compared with CNI. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6% of the patients and was lower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95% confidence interval: 0.31 to 0.70; p = 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95% confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (≤2 years) compared with late conversion (>2 years) after HT. Conclusions: Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.

KW - cardiac allograft vasculopathy

KW - coronary intravascular ultrasound

KW - heart transplantation

KW - immunosuppression

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