ImmunosuppressionLow-dose Tacrolimus/Sirolimus and Steroid Withdrawal in Heart Recipients Is Highly Efficacious
Section snippets
Study Design
The study was carried out as a single-center, prospective pilot study of primary heart transplant recipients. Thirty-three patients were notified with the intention to secure 30 evaluable patients (assuming a 10% drop-out rate), beginning enrollment in January 2001. The study was performed in accordance with the ethics principles described in the Declaration of Helsinki. The ethics committee of Ludwig Maximilian University, Munich, approved the protocol prior to study commencement. A single
Patient Demographics and Disposition
Prior to transplant, 17 of 33 (52%) patients were listed on the high-urgency waiting list. Time on the ventilator was 1.5 ± 0.9 days and 4.8 ± 2.2 days were required in intensive care. Demographics are summarized in Table 1. Eight patients received statins prior to transplant. After transplant, simvastatin (Zocor) was administered routinely to all patients from Weeks 1 to 2 onward.
All patients received study drug and were included for the 2-year follow-up. Three (9.1%) patients required a
Discussion
Based on the evidence of this open, prospective study, we have demonstrated the Tac–Rapa combination to be highly effective in the prevention of acute rejection in heart recipients. During the 2-year follow-up we observed just one acute rejection episode. This is consistent with a recently published report of a randomized, 3-arm study comparing Tac with MMF or Rapa vs CsA with MMF.7 Although there was no difference in survival between the three groups, the Tac/Rapa group had the lowest
References (13)
- et al.
Registry of the International Society for Heart and Lung Transplantation: twenty-second official adult heart transplant report—2005
J Heart Lung Transplant
(2005) Rapamune (RAPA, rapamycin, sirolimus)Mechanism of action immunosuppressive effect results from blockage of signal transduction and inhibition of cell cycle progression
Clin Biochem
(1998)- et al.
First experience with de novo calcineurin-inhibitor-free immunosuppression following cardiac transplantation
Transplantation
(2005) - et al.
Tacrolimus with mycophenolate mofetil (MMF) or sirolimus vs. cyclosporine with MMF in cardiac transplant patients: 1-year report
Am J Transplant
(2006) - et al.
Everolimus (Certican) in heart transplantation: optimizing renal function through minimizing cyclosporine exposure
Transplant Proc
(2005) - et al.
Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized clinical trial
Circulation
(2004)
Cited by (24)
De novo sirolimus with low-dose tacrolimus versus full-dose tacrolimus with mycophenolate mofetil after heart transplantation - 8-year results
2015, Journal of Heart and Lung TransplantationCitation Excerpt :Missing data in some sub-categories are due to the movement of 7 patients to another transplantation center. Study medication (initially intravenously, subsequently orally) was administered as described previously.11–14 All drugs were adjusted to defined target levels: in the lowTAC/SIR group, target TAC trough levels from 0 to 12 months 6 to 8 ng/ml, 2nd to 4th year 5 to 7 ng/ml, and 5th to 8th year 4 to 6 ng/ml and target SIR trough levels from 0 to 6 months 6 to 8 ng/ml and afterward 5 to 7 ng/ml; in the TAC/MMF group, target TAC trough levels from 0 to 6 months 13 to 15 ng/ml, 7 to 12 months 10 to 12 ng/ml, 2nd year 8 to 10 ng/ml, 3rd to 4th year 6 to 8 ng/ml, and 5th to 8th year 4 to 7 ng/ml, and target mycophenolic acid trough levels from 0 to 6 months 2.5 to 4.0 µg/ml, and 7 months to 8th year 1.5 to 2.5 µg/ml.
Use of mTOR inhibitors in chronic heart transplant recipients with renal failure: Calcineurin-inhibitors conversion or minimization?
2014, International Journal of CardiologyTacrolimus with mycophenolate mofetil or sirolimus compared with calcineurin inhibitor-free immunosuppression (sirolimus/mycophenolate mofetil) after heart transplantation: 5-year results
2013, Journal of Heart and Lung TransplantationImpact of different long-term maintenance immunosuppressive therapy strategies on patients' outcome after heart transplantation
2010, Transplant ImmunologyCitation Excerpt :At 12 months baseline creatinine increased to 144 ± 44 µM/l and it decreased again to 121 ± 35 µM/l by month 24. Survival was 100% and only one rejection was detected during the 24 month follow-up [70]. Based on these early experiences, there is agreement that CsA must be reduced to low levels in order to achieve the goal of renal function improvement with CsA + everolimus (or sirolimus), but there are as yet no data available on CsA target levels at which renal function can be improved without the risk of insufficient immunosuppression.
Immunosuppression Armamentarium in 2010: Mechanistic and Clinical Considerations
2010, Pediatric Clinics of North AmericaCitation Excerpt :In heart transplantation, benefits of MPA therapy were identified especially in regards to chronic graft vasculopathy.81 However, more recent data have revealed further improvement of this problem when using mTOR inhibitors in combination with CNI.82 The 2 main side effects of MPA are gastrointestinal problems, mainly diarrhea and abdominal pain, and bone marrow depression, leading to severe leucopenia and specifically lymphopenia.