BACKGROUND: The impact of long-term mycophenolate mofetil (MMF) treatment on the development of cardiac allograft vasculopathy (CAV) after heart transplantation is an area of much recent interest. This study analyzed the effects of various immunosuppressive combinations, including cyclosporine (CsA), azathioprine (Aza), tacrolimus (Tac) and MMF, on the time of onset, extent and progression of CAV. METHODS: Two hundred seventy-three consecutive heart transplant recipients (mean age: 51.2 +/- 12.2 years; mean follow-up: 6.8 +/- 1.9 years) were examined by coronary angiography on a yearly basis between 1995 and 2003. The extent of CAV was evaluated using a scoring system based on the severity of vessel stenosis. The onset of CAV was analyzed using Kaplan-Meier estimates and the log rank test for four treatment combinations, CsA/Aza (n = 47, 17.2%), CsA/MMF (n = 26, 9.5%), Tac/Aza (n = 62, 22.7%) and Tac/MMF (n = 138, 50.5%), and for the primary and the secondary immunosuppressants alone. RESULTS: The rate of freedom from CAV at 5 years was 47% with CsA/Aza, 66% with CsA/MMF, 60% with Tac/Aza and 70% with Tac/MMF. After 5 years, the Tac/MMF group showed a significantly lower incidence of CAV than the CsA/Aza group (log rank 7.58, p = 0.0059). CsA (n = 73) was compared with Tac (n = 200) and MMF (n = 164) with Aza (n = 109): the rate of freedom from CAV was 51.2% in CsA patients vs 66.1% in Tac patients (log rank 5.7, p = 0.017), and 54.6% in Aza patients vs 67% in MMF patients (log rank 4.36, p = 0.037). Multivariate Cox regression analysis revealed that MMF decreased the incidence of CAV significantly (p = 0.041). In this patient cohort, Tac or CsA medication was not an independent risk factor for incidence of CAV nor for decreased survival. CONCLUSIONS: The choice of immunosuppression has an impact on the incidence of CAV. In terms of prevention of CAV, MMF is superior to Aza in either combination. A trend toward improved survival in MMF patients was noted. The lower number of rejection episodes in the MMF groups may have contributed to these results.
BACKGROUND: The impact of long-term mycophenolate mofetil (MMF) treatment on the development of cardiac allograft vasculopathy (CAV) after heart transplantation is an area of much recent interest. This study analyzed the effects of various immunosuppressive combinations, including cyclosporine (CsA), azathioprine (Aza), tacrolimus (Tac) and MMF, on the time of onset, extent and progression of CAV. METHODS: Two hundred seventy-three consecutive heart transplant recipients (mean age: 51.2 +/- 12.2 years; mean follow-up: 6.8 +/- 1.9 years) were examined by coronary angiography on a yearly basis between 1995 and 2003. The extent of CAV was evaluated using a scoring system based on the severity of vessel stenosis. The onset of CAV was analyzed using Kaplan-Meier estimates and the log rank test for four treatment combinations, CsA/Aza (n = 47, 17.2%), CsA/MMF (n = 26, 9.5%), Tac/Aza (n = 62, 22.7%) and Tac/MMF (n = 138, 50.5%), and for the primary and the secondary immunosuppressants alone. RESULTS: The rate of freedom from CAV at 5 years was 47% with CsA/Aza, 66% with CsA/MMF, 60% with Tac/Aza and 70% with Tac/MMF. After 5 years, the Tac/MMF group showed a significantly lower incidence of CAV than the CsA/Aza group (log rank 7.58, p = 0.0059). CsA (n = 73) was compared with Tac (n = 200) and MMF (n = 164) with Aza (n = 109): the rate of freedom from CAV was 51.2% in CsApatients vs 66.1% in Tacpatients (log rank 5.7, p = 0.017), and 54.6% in Azapatients vs 67% in MMFpatients (log rank 4.36, p = 0.037). Multivariate Cox regression analysis revealed that MMF decreased the incidence of CAV significantly (p = 0.041). In this patient cohort, Tac or CsA medication was not an independent risk factor for incidence of CAV nor for decreased survival. CONCLUSIONS: The choice of immunosuppression has an impact on the incidence of CAV. In terms of prevention of CAV, MMF is superior to Aza in either combination. A trend toward improved survival in MMFpatients was noted. The lower number of rejection episodes in the MMF groups may have contributed to these results.
Authors: Sibylle von Vietinghoff; Ekaterina K Koltsova; Javier Mestas; Cody J Diehl; Joseph L Witztum; Klaus Ley Journal: J Am Coll Cardiol Date: 2011-05-24 Impact factor: 24.094
Authors: Bara Sarraj; Junsheng Ye; Ahmed Ibrahim Akl; Guodong Chen; Jiao-Jing Wang; Zheng Zhang; Farida Abadja; Michael Abecassis; Stephen D Miller; Geoffrey S Kansas; M Javeed Ansari Journal: Proc Natl Acad Sci U S A Date: 2014-08-04 Impact factor: 11.205
Authors: Kory J Lavine; Marc Sintek; Eric Novak; Gregory Ewald; Edward Geltman; Susan Joseph; John Pfeifer; Douglas L Mann Journal: Circ Heart Fail Date: 2013-05-24 Impact factor: 8.790
Authors: Frédéric A Houssiau; David D'Cruz; Shirish Sangle; Philippe Remy; Carlos Vasconcelos; Radmila Petrovic; Christoph Fiehn; Enrique de Ramon Garrido; Inge-Magrethe Gilboe; Maria Tektonidou; Daniel Blockmans; Isabelle Ravelingien; Véronique le Guern; Geneviève Depresseux; Loïc Guillevin; Ricard Cervera Journal: Ann Rheum Dis Date: 2010-09-10 Impact factor: 19.103