Long-term Results of Tacrolimus Monotherapy in Cardiac Transplant Recipients (original) (raw)
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Optimizing the immunosuppressive regimen in heart transplantation
The Journal of Heart and Lung Transplantation, 2004
The use of immunosuppression regimens containing a calcineurin inhibitor (CNI), an adjunct immunosuppressant (e.g., azathioprine, everolimus or mycophenolate mofetil) and corticosteroids has effectively reduced the risk of early graft loss due to acute rejection in heart transplant recipients. At present, late graft loss due to cardiac allograft vasculopathy (CAV) remains a major challenge for transplant teams. CAV is characterized by intimal hyperplasia as a result of endothelial cell injury. Factors relating to the transplant procedure itself (e.g., ischemic time and reperfusion injury), cardiovascular risks (e.g., donor age, hypertension, hyperlipidemia, pre-existing diabetes and new-onset diabetes after transplantation), immunologic risks (e.g., acute rejection episodes, anti-HLA antibodies) and the side effects of immunosuppression with CNIs or corticosteroids (e.g., cytomegalovirus infection, nephrotoxicity) have all been implicated in the development of CAV. The 2 main approaches to the prevention of CAV are modification of underlying risk factors (e.g., treatment with anti-hypertensive agents and lipid-lowering drugs, and optimizing the immunosuppressive regimen) and improvement in immunosuppression. CNIs remain the cornerstone of immunosuppressive regimens in heart transplantation, but new parameters for monitoring CNI exposure and new immunosuppressive regimens hold the promise of reduced overall CNI exposure with consequent reductions in vascular toxicity and improved clinical outcomes. Traditionally, trough levels of cyclosporine (C 0 ) have been used to monitor exposure to cyclosporine and to assess the need for dose adjustment. However, optimal cyclosporine exposure can now be achieved through monitoring of cyclosporine levels 2 hours after dosing (C 2 monitoring). Furthermore, in a pivotal trial in heart transplantation, the new proliferation signal inhibitor, everolimus, plus full-dose cyclosporine and corticosteroids, has been shown to have improved impact on prevention of biopsy-proven acute rejection (and other efficacy end-points) and longer term on the prevention of CAV. In addition, there is evidence from studies in renal transplant recipients that everolimus plus reduced exposure cyclosporine is effective and well tolerated-with the regimen having a reduced potential for CNI-related nephrotoxicity and for other CNI-related cardiovascular side effects. J Heart Lung Transplant 2004; 23:S207-13.
Drug design, development and therapy, 2014
The use of tacrolimus (TAC) in patients after heart transplantation (HTX) has increased over the last few years. In this retrospective study, we evaluated the effects of a TAC (conventional and extended-release TAC)-based immunosuppressive therapy regarding rejection profile in comparison to a cyclosporine A (CSA)-based regimen in patients after HTX. The data of 233 patients who underwent HTX at the Heidelberg Heart Transplantation Center from May 1998 until November 2010 were retrospectively analyzed. Primary immunosuppressive therapy was changed from a CSA (n=114) to a TAC (n=119)-based regimen in February 2006 according to center routine. Follow-up period was 2 years post-HTX. Primary endpoint was time to first biopsy-proven rejection requiring therapy. In all patients, routine follow-up at the Heidelberg Heart Transplantation Center was mandatory. Multivariate risk factor analysis regarding time to first rejection episode showed no statistically significant differences regarding...
Clinical Transplantation, 2007
Abstract: Background: The goal of immunosuppressive therapy in heart transplantation is to maximize safety and efficacy while minimizing morbidity and mortality. We now have numerous drug combinations, but few have been compared with each other.Aim: To compare various immunosuppressive regimens assessing morbidity and mortality at one yr.Methods: A total of 351 patients transplanted between 1989 and 2005 were included and grouped by immunosuppressive regimen into group 1 (n = 52): Muronomab (OKT3) 10 d, cyclosporine (CSA), azathioprine (AZA), steroids; group 2 (n = 193): OKT3 seven d, CSA, AZA, steroids; group 3 (n = 22): OKT3 seven d, CSA, mycophenolate mofetil (MMF), steroids; and group 4 (n = 84): interleukin-2 antagonists (IL-2), CSA, MMF, steroids.Results: The incidence of acute graft failure and treated rejection was similar between groups (17% and 78% respectively). We found a statistically significant difference in the incidence of infections (p < 0.001), renal dysfunction (p = 0.011) and in diabetes mellitus (p = 0.023). There were no differences in survival at 30 d (97%), but differences were found at one yr (p = 0.011). The multivariate analysis showed a strong association between mortality and infection (p = 0.001) and between survival and the group 4 regimen (p < 0.001).Conclusion: There are differences in survival at one yr of heart transplant patients depending on the immunosuppressive regimen used. The best combination was induction with IL-2 antagonists, followed by CSA, MMF and steroids.
Immunosuppressive Medication and Non-Rejection-Related Complications Following Heart Transplantation
Journal of Interdisciplinary Medicine, 2020
Background: Although the clinical evolution of a patient with heart failure is initially improved by transplantation, a number of potential complications may occur in the post-transplant period, which may be directly related to the effects of chronic immunosuppression. The purpose of this study was to analyze the occurrence and frequency of post-transplant complications related to immunosuppressive treatment in the Institute of Cardiovascular Diseases and Transplantation of Târgu Mureș, Romania. Material and methods: This is a descriptive study including 53 patients out of a total of 71 patients who underwent cardiac transplantation between 2000 and 2017 in the Institute of Cardiovascular Disease and Cardiac Transplantation in Târgu Mureș, Romania. Data were collected from the patient files and included demographic, clinical and laboratory data, as well as information about post-transplant complications related to immunosuppressive treatment. Results: The mean age of patients underg...
Journal of Cardiology Cases, 2012
We report on a 25-year-old female heart transplant patient who presented with recurrent episodes of cellular rejection due to decreased adherence to immunosuppressive therapy. She received a heart transplantation in 1994 when she was 10 years old. In order to improve her adherence to immunosuppressive therapy, switching to the once-daily extended-release formulation of tacrolimus was performed in a step-wise fashion. First, the twice-daily formulation of cyclosporin A was replaced with the twice-daily preparation of tacrolimus. When the trough blood levels of tacrolimus reached a plateau in the range of 5.0 ng/mL, it was changed to the once-daily extended-release formulation of tacrolimus after confirming the absence of new rejection episodes. There were no significant changes in renal function before and after the switch. After being discharged from the hospital, the patient made significant advancements in adherence to immunosuppressive therapy. Her subsequent clinical course was uneventful, with no adverse events observed. Most patients who undergo solid organ transplantation must receive lifelong immunosuppressive therapy. This case demonstrates that conversion to the extended-release formulation of tacrolimus from other calcineurin inhibitor preparations is a reasonable choice to consider in the management of compromised immunosuppressive therapy adherence in heart transplant patients during the late posttransplant period.
Clinical results of steroid-free induction immunosuppression after heart transplantation
Annals of Thoracic Surgery, 1993
112 operative survivors of heart transplantation were initially immunosuppressed with cyclosporin A and azathioprine without prednisone. Eighty-eight patients (79%) remained on a regimen of double therapy for a mean follow-up of 25 f 15 months (range, 1 to 54 months), whereas 24 patients (21%) had oral prednisone, 5 mg/day, added to maintenance therapy for persistent or repeated rejection. There were 5 early deaths (4%) because of acute rejection (4 patients) or infection (1 patient). Only 1 patient died late after heart transplantation of chronic rejection. Actuarial survival was 95% f 2% and 94% f 3% at 12 and 48 months, respectively. Mean rate of acute rejection was 1.7 f 1.0 episodes per patient, with a 5% f 2% freedom he developments in immunosuppressive therapy T have resulted in improved survival and reduced morbidity after heart transplantation [l]. Although the clinical results obtained using cyclosporine, azathioprine, and steroids as maintenance immunosuppression have been extensively reported [l, 21, the definitive role of steroids continues to be questioned [3, 41. Much concern remains about the complications of long-term steroid administration in regard to the incidence of opportunistic infections, hypertension, diabetes, hyperlipidemia, obesity, osteoporosis, and retarded growth [3, 51. Further-For editorial comment, see page 1069. more, the role of steroids in the development of accelerated graft atherosclerosis is still uncertain [l, 61. The early and late advantages of corticosteroid withdrawal and of steroid-free maintenance immunosuppression have already been described [7]. However, the long-term results obtained after heart transplantation with a cyclosporineand azathioprine-based induction therapy have not been thoroughly assessed. For this purpose, we have retrospectively analyzed the clinical outcome of heart transplantation using a steroid-free induction immunosuppressive therapy.
ARS Medica Tomitana, 2012
In a retrospective study, the safety profile and efficacy of immunosuppressive medication was evaluated in 35 patients with cardiac transplant in Targu Mures during 1999-2011 (11 treated with cyclosporine, 24 with tacrolimus, both drugs were associated with mycophenolate mofetil). Therapeutic benefit was measured by survival curve and lack of rejection while safety was evaluated by measuring plasma immunosuppressive drugs levels and evaluation of specific adverse events (nephrotoxicity, diabetes, and hypertension). The most frequent side effect was nephrotoxicity (significant reduction in glomerular filtration rate estimated by MDRD formula), but no significant differences were found between the 2 medications.
Transplantation proceedings, 2012
Organ transplant recipients with refractory rejection or intolerance to the prescribed immunosuppressant may respond to rescue therapy with tacrolimus. We sought to evaluate the clinical outcomes of children undergoing heart transplantation who required conversion from a cyclosporine-based, steroid-free therapy to a tacrolimus-based regimen. We performed a prospective, observational, cohort study of 28 children who underwent conversion from cyclosporine-based, steroid-free therapy to a tacrolimus-based therapy for refractory or late rejection or intolerance to cyclosporine. There was complete resolution of refractory rejection episodes and adverse side effects in all patients. The incidence rate (×100) of rejection episodes before and after conversion was 7.98 and 2.11, respectively (P ≤ .0001). There was a 25% mortality rate in patients using tacrolimus after a mean period of 60 months after conversion. Tacrolimus is effective as rescue therapy for refractory rejection and is a the...
Physiological research / Academia Scientiarum Bohemoslovaca, 2010
Despite the widespread use of potent immunosuppressive drugs, such as cyclosporin A and mycophenolate mofetil, ongoing and recurrent cellular rejection remain a common problem after heart transplantation. We aimed to describe the long-term effects of conversion from cyclosporine A to tacrolimus in patients with ongoing and recurrent cellular rejection. This was a single-centre retrospective analysis of 17 heart transplant recipients who were switched from cyclosporine A to tacrolimus due to ongoing (5 patients) or recurrent cellular rejection (12 patients). We studied long-term efficacy and safety of this approach. 167 endomyocardial biopsies were performed during a mean follow-up of 69.1 +/- 12.7 months. Thirteen biopsies (7.8%) in eight patients (47%) revealed higher grades of acute cellular rejection (Banff 2). However, they were not hemodynamically significant and did not require intravenous antirejection therapy. The mean rejection score was reduced significantly. Conversion to...